aminoglycosides

Summary

Summary: Glycosylated compounds in which there is an amino substituent on the glycoside. Some of them are clinically important ANTIBIOTICS.

Top Publications

  1. ncbi Structural basis of transcription inhibition by antibiotic streptolydigin
    Dmitry Temiakov
    Department of Cell Biology, School of Osteopathic Medicine, University of Medicine and Dentistry of New Jersey, Stratford, New Jersey 08084, USA
    Mol Cell 19:655-66. 2005
  2. pmc Metabolite-enabled eradication of bacterial persisters by aminoglycosides
    Kyle R Allison
    Howard Hughes Medical Institute, Department of Biomedical Engineering, Center for BioDynamics and Center for Advanced Biotechnology, Boston University, Boston, Massachusetts 02215, USA
    Nature 473:216-20. 2011
  3. ncbi FM1-43 dye behaves as a permeant blocker of the hair-cell mechanotransducer channel
    J E Gale
    School of Biological Sciences, University of Sussex, Falmer, Brighton, BN1 9QG, United Kingdom
    J Neurosci 21:7013-25. 2001
  4. ncbi Fe-S cluster biosynthesis controls uptake of aminoglycosides in a ROS-less death pathway
    Benjamin Ezraty
    Laboratoire de Chimie Bacterienne, Aix Marseille Universite, CNRS, UMR 7283, Institut de Microbiologie de la Mediterranee, 31 Chemin Joseph Aiguier, 13009 Marseille France
    Science 340:1583-7. 2013
  5. ncbi Fidaxomicin versus vancomycin for Clostridium difficile infection
    Thomas J Louie
    University of Calgary, Calgary, AB, Canada
    N Engl J Med 364:422-31. 2011
  6. pmc Mistranslation of membrane proteins and two-component system activation trigger antibiotic-mediated cell death
    Michael A Kohanski
    Department of Biomedical Engineering, Center for BioDynamics, and Center for Advanced Biotechnology, Boston University, Boston, MA 02215, USA
    Cell 135:679-90. 2008
  7. pmc Multiplex PCR for detection of aminoglycoside resistance genes in enterococci
    Sergei B Vakulenko
    Division of Infectious Diseases, Department of Biochemistry and Molecular Biology, Wayne State University, Detroit, Michigan 48201, USA
    Antimicrob Agents Chemother 47:1423-6. 2003
  8. ncbi Polyamines reduce oxidative stress in Escherichia coli cells exposed to bactericidal antibiotics
    Alexander G Tkachenko
    Laboratory of Microbial Adaptation, Institute of Ecology and Genetics of Microorganisms UB RAS, 13 Golev str, Perm 614081, Russia
    Res Microbiol 163:83-91. 2012
  9. ncbi A new macrocyclic antibiotic, fidaxomicin (OPT-80), causes less alteration to the bowel microbiota of Clostridium difficile-infected patients than does vancomycin
    Gerald W Tannock
    Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand
    Microbiology 156:3354-9. 2010
  10. pmc The aminoglycoside antibiotic dihydrostreptomycin rapidly enters mouse outer hair cells through the mechano-electrical transducer channels
    Walter Marcotti
    School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG, UK
    J Physiol 567:505-21. 2005

Detail Information

Publications293 found, 100 shown here

  1. ncbi Structural basis of transcription inhibition by antibiotic streptolydigin
    Dmitry Temiakov
    Department of Cell Biology, School of Osteopathic Medicine, University of Medicine and Dentistry of New Jersey, Stratford, New Jersey 08084, USA
    Mol Cell 19:655-66. 2005
    ..The results provide a basis for a design of new antibiotics utilizing the Stl-like mechanism...
  2. pmc Metabolite-enabled eradication of bacterial persisters by aminoglycosides
    Kyle R Allison
    Howard Hughes Medical Institute, Department of Biomedical Engineering, Center for BioDynamics and Center for Advanced Biotechnology, Boston University, Boston, Massachusetts 02215, USA
    Nature 473:216-20. 2011
    ..killing of both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) persisters with aminoglycosides. This potentiation is aminoglycoside-specific, it does not rely on growth resumption and it is effective in ..
  3. ncbi FM1-43 dye behaves as a permeant blocker of the hair-cell mechanotransducer channel
    J E Gale
    School of Biological Sciences, University of Sussex, Falmer, Brighton, BN1 9QG, United Kingdom
    J Neurosci 21:7013-25. 2001
    ..Calcium chelation and FM1-43 both reduce the ototoxic effects of the aminoglycoside antibiotic neomycin sulfate, suggesting that FM1-43 and aminoglycosides enter hair cells via the same pathway.
  4. ncbi Fe-S cluster biosynthesis controls uptake of aminoglycosides in a ROS-less death pathway
    Benjamin Ezraty
    Laboratoire de Chimie Bacterienne, Aix Marseille Universite, CNRS, UMR 7283, Institut de Microbiologie de la Mediterranee, 31 Chemin Joseph Aiguier, 13009 Marseille France
    Science 340:1583-7. 2013
    ..Furthermore, we demonstrate that Fe-S clusters are required for killing only by aminoglycosides. In contrast to cells, using the major Fe-S cluster biosynthesis machinery, ISC, cells using the alternative ..
  5. ncbi Fidaxomicin versus vancomycin for Clostridium difficile infection
    Thomas J Louie
    University of Calgary, Calgary, AB, Canada
    N Engl J Med 364:422-31. 2011
    ..This phase 3 clinical trial compared the efficacy and safety of fidaxomicin with those of vancomycin in treating C. difficile infection...
  6. pmc Mistranslation of membrane proteins and two-component system activation trigger antibiotic-mediated cell death
    Michael A Kohanski
    Department of Biomedical Engineering, Center for BioDynamics, and Center for Advanced Biotechnology, Boston University, Boston, MA 02215, USA
    Cell 135:679-90. 2008
    ..Here, we use systems-level approaches and phenotypic analyses to provide insight into the pathway whereby aminoglycosides ultimately trigger hydroxyl radical formation...
  7. pmc Multiplex PCR for detection of aminoglycoside resistance genes in enterococci
    Sergei B Vakulenko
    Division of Infectious Diseases, Department of Biochemistry and Molecular Biology, Wayne State University, Detroit, Michigan 48201, USA
    Antimicrob Agents Chemother 47:1423-6. 2003
    ....
  8. ncbi Polyamines reduce oxidative stress in Escherichia coli cells exposed to bactericidal antibiotics
    Alexander G Tkachenko
    Laboratory of Microbial Adaptation, Institute of Ecology and Genetics of Microorganisms UB RAS, 13 Golev str, Perm 614081, Russia
    Res Microbiol 163:83-91. 2012
    Bactericidal antibiotics (fluoroquinolones, aminoglycosides and cephalosporins) at their sublethal concentrations were able to produce hydroxyl radicals, hydrogen peroxide and superoxide anions (ROS) in Escherichia coli cells, which ..
  9. ncbi A new macrocyclic antibiotic, fidaxomicin (OPT-80), causes less alteration to the bowel microbiota of Clostridium difficile-infected patients than does vancomycin
    Gerald W Tannock
    Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand
    Microbiology 156:3354-9. 2010
    ..These findings help to explain the substantially reduced rates of relapse following treatment of CDI with fidaxomicin in recent clinical trials...
  10. pmc The aminoglycoside antibiotic dihydrostreptomycin rapidly enters mouse outer hair cells through the mechano-electrical transducer channels
    Walter Marcotti
    School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QG, UK
    J Physiol 567:505-21. 2005
    ....
  11. ncbi Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study
    Sylvie Castaigne
    Hôpital Mignot, Université Versailles Saint Quentin, Le Chesnay, France
    Lancet 379:1508-16. 2012
    ..We investigated whether the addition of low fractionated-dose gemtuzumab ozogamicin to standard front-line chemotherapy would improve the outcome of patients with this leukaemia without causing excessive toxicity...
  12. pmc Maternally inherited aminoglycoside-induced and nonsyndromic deafness is associated with the novel C1494T mutation in the mitochondrial 12S rRNA gene in a large Chinese family
    Hui Zhao
    Division and Program in Human Genetics and Center for Hearing and Deafness Research, Cincinnati Children s Hospital Medical Center, Cincinnati, OH 45229 3039, USA
    Am J Hum Genet 74:139-52. 2004
    ..In the absence of aminoglycosides, some matrilineal relatives in this family exhibited late-onset/progressive deafness, with a wide range of ..
  13. ncbi Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial
    Oliver A Cornely
    University Hospital Cologne, Cologne, Germany
    Lancet Infect Dis 12:281-9. 2012
    ..We aimed to compare efficacy and safety of fidaxomicin and vancomycin to treat patients with C difficile infection in Europe, Canada, and the USA...
  14. ncbi The Lon protease of Pseudomonas aeruginosa is induced by aminoglycosides and is involved in biofilm formation and motility
    Alexandra K Marr
    Centre for Microbial Diseases and Immunity Research, University of British Columbia, 2259 Lower Mall, Vancouver, British Columbia V6T 1Z4, Canada
    Microbiology 153:474-82. 2007
    ..Serious infections by this organism are often treated with a combination of aminoglycosides and semi-synthetic penicillins...
  15. pmc Versatility of aminoglycosides and prospects for their future
    Sergei B Vakulenko
    Department of Chemistry, Wayne State University, Detroit, Michigan 48202, USA
    Clin Microbiol Rev 16:430-50. 2003
    ..This article reviews the most recent knowledge about the mechanisms of aminoglycoside action and the mechanisms of resistance to these antibiotics...
  16. ncbi Glomerular nephrotoxicity of aminoglycosides
    Carlos Martinez-Salgado
    Unidad de Investigacion, Hospital Universitario de Salamanca, Paseo San Vicente 58 182, 37007 Salamanca, Spain
    Toxicol Appl Pharmacol 223:86-98. 2007
    ..However, aminoglycosides induce nephrotoxicity in 10-20% of therapeutic courses...
  17. pmc Aminoglycoside modifying enzymes
    Maria S Ramirez
    Center for Applied Biotechnology Studies, Department of Biological Science, College of Natural Sciences and Mathematics, California State University Fullerton, Fullerton, CA 92834 6850, USA
    Drug Resist Updat 13:151-71. 2010
    b>Aminoglycosides have been an essential component of the armamentarium in the treatment of life-threatening infections. Unfortunately, their efficacy has been reduced by the surge and dissemination of resistance...
  18. ncbi The future of aminoglycosides: the end or renaissance?
    Jacob L Houghton
    Department of Medicinal Chemistry in the College of Pharmacy, University of Michigan, 210 Washtenaw Avenue, Ann Arbor, MI 48109, USA
    Chembiochem 11:880-902. 2010
    Although aminoglycosides have been used as antibacterials for decades, their use has been hindered by their inherent toxicity and the resistance that has emerged to these compounds...
  19. ncbi Activity of aminoglycosides, including ACHN-490, against carbapenem-resistant Enterobacteriaceae isolates
    D M Livermore
    Antibiotic Resistance Monitoring and Reference Laboratory, HPA Microbiology Services, London, UK
    J Antimicrob Chemother 66:48-53. 2011
    ..Comparators included internationally and locally available aminoglycosides. Methods The isolates variously had KPC (n = 12), SME-1 (n = 1), IMP (n = 13), VIM (n = 5), NDM (n = 17) or ..
  20. ncbi Cellular mechanisms of aminoglycoside ototoxicity
    Mark E Warchol
    Department of Otolaryngology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Curr Opin Otolaryngol Head Neck Surg 18:454-8. 2010
    ..To summarize advances in the study of the interaction between sensory hair cells and aminoglycoside antibiotics...
  21. pmc The BpeAB-OprB efflux pump of Burkholderia pseudomallei 1026b does not play a role in quorum sensing, virulence factor production, or extrusion of aminoglycosides but is a broad-spectrum drug efflux system
    Takehiko Mima
    Department of Microbiology, Immunology and Pathology, Colorado State University, IDRC at Foothills Campus, Campus Delivery 2025, Fort Collins, CO 80523 2025, USA
    Antimicrob Agents Chemother 54:3113-20. 2010
    ..despite the fact that they also encode and express BpeAB-OprB, which was reported to mediate efflux of aminoglycosides in the Singapore strain KHW. To reassess the role of BpeAB-OprB in B...
  22. ncbi RNA sequence determinants for aminoglycoside binding to an A-site rRNA model oligonucleotide
    M I Recht
    Department of Chemistry and Biochemistry, University of California, Santa Cruz 95064, USA
    J Mol Biol 262:421-36. 1996
    ..Oligonucleotides homologous to eukaryotic rRNA sequences show reduced binding of paromomycin, suggesting a physical origin for the species-specific action of aminoglycosides.
  23. ncbi Bacterial resistance to aminoglycoside antibiotics
    J Davies
    Dept of Microbiology and Immunology, University of British Columbia, Vancouver, Canada
    Trends Microbiol 5:234-40. 1997
    ..of the current concerns over the global rise in antibiotic-resistant microorganisms, there has been renewed interest in the mechanisms of resistance to the aminoglycosides, including the superfamily of aminoglycoside-modifying enzymes.
  24. ncbi Aminoglycosides versus bacteria--a description of the action, resistance mechanism, and nosocomial battleground
    Shazi Shakil
    Interdisciplinary Biotechnology Unit, Aligarh Muslim University, 202002, Aligarh, India
    J Biomed Sci 15:5-14. 2008
    Since 1944, we have come a long way using aminoglycosides as antibiotics. Bacteria also have got them selected with hardier resistance mechanisms...
  25. ncbi Aminoglycoside induced ototoxicity
    O neil W Guthrie
    Duke University, Department of Biology, Developmental, Cell and Molecular Biology DCMB Group, French Family Science Center, Durham, NC 27708 0338, USA
    Toxicology 249:91-6. 2008
    b>Aminoglycosides are bactericidal aminoglycosidic aminocyclitols. They are cost effective and therefore widely used, however ototoxicity is a prominent dose-limiting side effect...
  26. pmc Beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy for fever with neutropenia: systematic review and meta-analysis
    Mical Paul
    Rabin Medical Centre, Beilinson Campus, Infectious Diseases Unit and Department of Medicine E, Petah Tiqva 49100, Israel
    BMJ 326:1111. 2003
    ..To compare the effectiveness of beta lactam monotherapy versus beta lactam-aminoglycoside combination therapy in the treatment of patients with fever and neutropenia...
  27. pmc Identification of genetic and chemical modulators of zebrafish mechanosensory hair cell death
    Kelly N Owens
    Department of Biological Structure, University of Washington, Seattle, Washington, United States of America
    PLoS Genet 4:e1000020. 2008
    ..The combination of chemical screening with traditional genetic approaches is a new strategy for identifying drugs and drug targets to attenuate hearing and balance disorders...
  28. pmc Relapse versus reinfection: recurrent Clostridium difficile infection following treatment with fidaxomicin or vancomycin
    Iris Figueroa
    Hines Veterans Affairs Hospital, Hines, IL 60141, USA
    Clin Infect Dis 55:S104-9. 2012
    ..Caution in generalizing these observations is required, because the patients studied were younger and more likely to be from Canadian sites than were patients with recurrence who did not provide isolates...
  29. ncbi Association of the novel aminoglycoside resistance determinant RmtF with NDM carbapenemase in Enterobacteriaceae isolated in India and the UK
    Laura Hidalgo
    Department of Animal Health and VISAVET, Universidad Complutense de Madrid, Madrid, Spain
    J Antimicrob Chemother 68:1543-50. 2013
    16S rRNA methyltransferases are an emerging mechanism conferring high-level resistance to clinically relevant aminoglycosides and have been associated with important mechanisms such as NDM-1...
  30. pmc Increased selectivity toward cytoplasmic versus mitochondrial ribosome confers improved efficiency of synthetic aminoglycosides in fixing damaged genes: a strategy for treatment of genetic diseases caused by nonsense mutations
    Jeyakumar Kandasamy
    The Edith and Joseph Fischer Enzyme Inhibitors Laboratory, Schulich Faculty of Chemistry, Technion Israel Institute of Technology, Haifa 32000, Israel
    J Med Chem 55:10630-43. 2012
    ..a series of biochemical assays, we provide proof of principle that antibacterial activity and toxicity of aminoglycosides can be dissected from their suppression activity...
  31. pmc Rational design of bioactive, modularly assembled aminoglycosides targeting the RNA that causes myotonic dystrophy type 1
    Jessica L Childs-Disney
    Department of Chemistry, Scripps Florida, 130 Scripps Way, Jupiter, FL 33458, USA
    ACS Chem Biol 7:1984-93. 2012
    ..Modest improvement of pre-mRNA splicing defects was observed. These studies suggest that a modular assembly approach can afford bioactive compounds that target RNA...
  32. ncbi The occurrence of virulence traits among high-level aminoglycosides resistant Enterococcus isolates obtained from feces of humans, animals, and birds in South Korea
    Dukki Han
    Department of Environmental Science and Engineering, Gwangju 500 712, Republic of Korea
    Int J Food Microbiol 144:387-92. 2011
    ..wild geese, and humans, respectively, yielded Enterococcus isolates that were resistant to high-levels of aminoglycosides (i.e., of gentamicin, kanamycin, and streptomycin, minimum inhibitory concentrations were >1000 mg/l)...
  33. pmc Fidaxomicin versus vancomycin for Clostridium difficile infection: meta-analysis of pivotal randomized controlled trials
    Derrick W Crook
    Nuffield Department of Medicine, Oxford University, Oxford, UK
    Clin Infect Dis 55:S93-103. 2012
    ..01). Fidaxomicin has the potential to substantially improve outcomes from CDI...
  34. ncbi Assessment of 6'- and 6'''-N-acylation of aminoglycosides as a strategy to overcome bacterial resistance
    Pazit Shaul
    School of Chemistry, Tel Aviv University, Tel Aviv, 69978, Israel
    Org Biomol Chem 9:4057-63. 2011
    ..Our study indicates that as for 1-N-acylation, 6'- and 6'''-N-acylation of aminoglycosides offer an additional promising direction in the search for aminoglycosides capable of overcoming infections by ..
  35. pmc Killing kinetics of fidaxomicin and its major metabolite, OP-1118, against Clostridium difficile
    FARAH BABAKHANI
    Optimer Pharmaceuticals, San Diego, CA, USA
    J Med Microbiol 60:1213-7. 2011
    ..difficile strains, including the hypervirulent restriction endonuclease analysis group BI strains, at concentrations that are many fold below the detected faecal concentrations of these compounds after oral administration of fidaxomicin...
  36. pmc Comparative effectiveness of aminoglycosides, polymyxin B, and tigecycline for clearance of carbapenem-resistant Klebsiella pneumoniae from urine
    Michael J Satlin
    Department of Medicine, Weill Cornell Medical College, New York, New York 10021, USA
    Antimicrob Agents Chemother 55:5893-9. 2011
    ..with in vitro activity against CRKP are typically limited to polymyxins, tigecycline, and often, aminoglycosides. We conducted a retrospective cohort study of cases of CRKP bacteriuria at New York-Presbyterian Hospital ..
  37. ncbi Amelioration of aminoglycoside nephrotoxicity requires protection of renal mitochondria
    Dmitry B Zorov
    Department of Bioenergetics, A N Belozersky Institute of Physico Chemical Biology, Moscow State University, Moscow, Russia
    Kidney Int 77:841-3. 2010
    ..Morales et al. reveal that the antidiabetic drug metformin prevents gentamicin-induced nephropathy through a mitochondria-dependent pathway, normalizing oxidative stress and restoring mitochondrial functional integrity...
  38. ncbi Molecular insights into aminoglycoside action and resistance
    Sophie Magnet
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Chem Rev 105:477-98. 2005
  39. ncbi Cubilin and megalin co-localize in the neonatal inner ear
    Jacob Tauris
    Department of Otorhinolaryngology, Aarhus University Hospital, Aarhus, Denmark
    Audiol Neurootol 14:267-78. 2009
    ..Furthermore, we examined the binding properties of 6 different aminoglycosides (AGs) to cubilin and compared the results to data obtained for megalin, which is a well-known receptor for ..
  40. ncbi Resistance due to aminoglycoside modifying enzymes in Pseudomonas aeruginosa isolates from burns patients
    M Shahid
    Department of Microbiology, J N Medical College and Hospital, Aligarh Muslim University, Aligarh, India
    Indian J Med Res 122:324-9. 2005
    Enzymatic modifications of aminoglycosides result in high-level resistance in numerous bacterial species. However, the data on this aspect are elementary in our country...
  41. ncbi Pharmaceuticals targeting nonsense mutations in genetic diseases: progress in development
    Steven M Rowe
    Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35233, USA
    BioDrugs 23:165-74. 2009
    ..Several ribosome-binding drugs, including select aminoglycosides and synthetic novel small molecules, induce 'translational readthrough' of PTCs, restoring full-length ..
  42. pmc MexXY-OprM efflux pump is necessary for a adaptive resistance of Pseudomonas aeruginosa to aminoglycosides
    Didier Hocquet
    Laboratoire de Bacteriologie, Hopital Jean Minjoz, Besancon, France
    Antimicrob Agents Chemother 47:1371-5. 2003
    Exposure of Pseudomonas aeruginosa to aminoglycosides frequently selects for recalcitrant subpopulations exhibiting an unstable, "adaptive" resistance to these antibiotics...
  43. pmc Efficacy of fidaxomicin versus vancomycin as therapy for Clostridium difficile infection in individuals taking concomitant antibiotics for other concurrent infections
    Kathleen M Mullane
    Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA
    Clin Infect Dis 53:440-7. 2011
    ..We used data from 2 phase 3 trials to study effects of CAs on response to fidaxomicin or vancomycin...
  44. ncbi Molecular understanding of aminoglycoside action and resistance
    S Jana
    Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology, New Delhi
    Appl Microbiol Biotechnol 70:140-50. 2006
    b>Aminoglycosides are potent bactericidal antibiotics targeting the bacterial ribosome, where they bind to the A-site and disrupt protein synthesis...
  45. pmc Telavancin versus vancomycin for hospital-acquired pneumonia due to gram-positive pathogens
    Ethan Rubinstein
    Section of Infectious Diseases Department of Internal Medicine and Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada
    Clin Infect Dis 52:31-40. 2011
    ..Telavancin is a lipoglycopeptide bactericidal against gram-positive pathogens...
  46. pmc Widespread dissemination of aminoglycoside resistance genes armA and rmtB in Klebsiella pneumoniae isolates in Taiwan producing CTX-M-type extended-spectrum beta-lactamases
    Ling Ma
    Division of Clinical Research, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan
    Antimicrob Agents Chemother 53:104-11. 2009
    ..pneumoniae isolates carrying armA or rmtB. In conclusion, the concomitant presence of a 16S rRNA methylase gene (armA or rmtB) and bla(CTX-M) among amikacin-resistant ESBL-producing K. pneumoniae isolates is widespread in Taiwan...
  47. ncbi Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial
    Alan K Burnett
    Department of Haematology, Cardiff University School of Medicine, Heath Park, Cardiff, United Kingdom
    J Clin Oncol 29:369-77. 2011
    ..We previously established that it is feasible to combine GO with conventional chemotherapy. We now report a large randomized trial testing the addition of GO to induction and/or consolidation chemotherapy in untreated younger patients...
  48. ncbi Aminoglycoside ototoxicity in adult CBA, C57BL and BALB mice and the Sprague-Dawley rat
    W J Wu
    Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, 1301 East Ann Street, Ann Arbor, MI 48109-0506, USA
    Hear Res 158:165-78. 2001
    ..Pigmentation, however, paralleled this rank order suggesting an influence of melanin on cochlear antioxidant status...
  49. ncbi Structure of an enzyme required for aminoglycoside antibiotic resistance reveals homology to eukaryotic protein kinases
    W C Hon
    Department of Biochemistry, McMaster University, Hamilton, Ontario, Canada
    Cell 89:887-95. 1997
    ..These results indicate that APH(3') enzymes and eukaryotic-type protein kinases share a common ancestor...
  50. pmc Role of the multidrug efflux system MexXY in the emergence of moderate resistance to aminoglycosides among Pseudomonas aeruginosa isolates from patients with cystic fibrosis
    Christelle Vogne
    Laboratoire de Bacteriologie, Hopital Jean Minjoz, F 25030 Besancon, France
    Antimicrob Agents Chemother 48:1676-80. 2004
    ..These data indicate that a locus different from mexZ may be involved in overproduction of MexXY and that other nonenzymatic mechanisms contribute to AG resistance in P. aeruginosa...
  51. ncbi Genetic factors in aminoglycoside toxicity
    Nathan Fischel-Ghodsian
    Cedars Sinai Medical Center, Department of Pediatrics, Suite 1165WT, 8700 Beverly Blvd, Los Angeles, CA 90048, USA
    Pharmacogenomics 6:27-36. 2005
    Ototoxicity is the major irreversible toxicity of aminoglycosides, and it occurs both in a dose-dependent and idiosyncratic fashion...
  52. pmc Structural, functional, and genetic analysis of sorangicin inhibition of bacterial RNA polymerase
    Elizabeth A Campbell
    The Rockefeller University, New York, NY 10021, USA
    EMBO J 24:674-82. 2005
    ..We suggest that conformational flexibility of Sor, in contrast to the rigid conformation of Rif, allows Sor to adapt to changes in the binding pocket. This has important implications for drug design against rapidly mutating targets...
  53. ncbi The pleiotropic regulator AdpA-L directly controls the pathway-specific activator of nikkomycin biosynthesis in Streptomyces ansochromogenes
    Yuanyuan Pan
    State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Science, Beijing, China
    Mol Microbiol 72:710-23. 2009
    ..Meanwhile, nikkomycin production of the mutated site III strain was enhanced comparing with the wild-type strain as control. This work highlights a new level of complexity in the regulation of nikkomycin biosynthesis...
  54. ncbi Genetic basis of resistance to aminoglycosides in Acinetobacter spp. and spread of armA in Acinetobacter baumannii sequence group 1 in Korean hospitals
    Yoo Jin Cho
    Department of Microbiology, Kyungpook National University School of Medicine, Dongin Dong, Jung Gu, Daegu, South Korea
    Diagn Microbiol Infect Dis 64:185-90. 2009
    A total of 75 Acinetobacter isolates resistant to all available aminoglycosides obtained from 2 Korean hospitals were studied for the genetic basis of resistance to aminoglycosides...
  55. ncbi Do we still need the aminoglycosides?
    Emanuele Durante-Mangoni
    Unit of Infectious and Transplant Medicine, 2nd University of Naples, Monaldi Hospital, Naples, Italy
    Int J Antimicrob Agents 33:201-5. 2009
    ..This has raised doubts regarding the actual clinical utility of aminoglycosides. However, the recent emergence of infections due to Gram-negative bacterial strains with advanced patterns of ..
  56. ncbi Structural basis for substrate loading in bacterial RNA polymerase
    Dmitry G Vassylyev
    Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Schools of Medicine and Dentistry, 402B Kaul Genetics Building, 720 20th Street South, Birmingham, Alabama 35294, USA
    Nature 448:163-8. 2007
    ..Second, freezing of the preinsertion state is an attractive target for the design of novel antibiotics. Last, the TL emerges as a prominent target whose refolding can be modulated by regulatory factors...
  57. ncbi High-level antibiotic resistance in Pseudomonas aeruginosa biofilm: the ndvB gene is involved in the production of highly glycerol-phosphorylated beta-(1->3)-glucans, which bind aminoglycosides
    Irina Sadovskaya
    Univ Lille Nord de France, F 59000 Lille, France
    Glycobiology 20:895-904. 2010
    ..This observation fills a gap in our understanding of the relationship between biofilm, cyclic glucans and high-level antibiotic resistance...
  58. pmc Plasmid-mediated high-level resistance to aminoglycosides in Enterobacteriaceae due to 16S rRNA methylation
    Marc Galimand
    Unite des Agents Antibacteriens, Institut Pasteur, 75724 Paris Cedex 15, France
    Antimicrob Agents Chemother 47:2565-71. 2003
    ..resistance to streptomycin-spectinomycin was due to the ant3"9 gene, and resistance to nearly all remaining aminoglycosides was due to the aac3-II gene and a new gene designated armA (aminoglycoside resistance methylase)...
  59. ncbi 16S ribosomal RNA methylation: emerging resistance mechanism against aminoglycosides
    Yohei Doi
    Division of Infectious Diseases, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA
    Clin Infect Dis 45:88-94. 2007
    Methylation of 16S ribosomal RNA (rRNA) has recently emerged as a new mechanism of resistance against aminoglycosides among gram-negative pathogens belonging to the family Enterobacteriaceae and glucose-nonfermentative microbes, ..
  60. ncbi Aminoglycoside ototoxicity
    Mark Douglas Rizzi
    Head and Neck Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA
    Curr Opin Otolaryngol Head Neck Surg 15:352-7. 2007
    ..To summarize mechanisms of ototoxicity associated with aminoglycoside antibiotics and discuss possible protective strategies...
  61. pmc Inactivation of KsgA, a 16S rRNA methyltransferase, causes vigorous emergence of mutants with high-level kasugamycin resistance
    Kozo Ochi
    National Food Research Institute, Tsukuba, Ibaraki, Japan
    Antimicrob Agents Chemother 53:193-201. 2009
    ..We propose that the ksgA mutation, together with the rsmG mutation, may provide a novel clue to uncover a still-unknown mechanism of mutation and ribosomal function...
  62. pmc CD33 expression and P-glycoprotein-mediated drug efflux inversely correlate and predict clinical outcome in patients with acute myeloid leukemia treated with gemtuzumab ozogamicin monotherapy
    Roland B Walter
    Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 1024, USA
    Blood 109:4168-70. 2007
    ..The inverse relationship between CD33 and Pgp suggests a maturation-stage-dependent expression of both proteins, and offers the rationale for using cell differentiation-promoting agents to enhance GO-induced cytotoxicity...
  63. pmc Aminoglycoside resistance in Pseudomonas aeruginosa
    Keith Poole
    Department of Microbiology and Immunology, Rm 737 Botterell Hall, Queen s University, Kingston, ON K7L 3N6, Canada
    Antimicrob Agents Chemother 49:479-87. 2005
  64. ncbi Ototoxicity
    L P Rybak
    Department of Surgery, Southern Illinois University, School of Medicine, Springfield, Illinois 62794 9653, USA
    Kidney Int 72:931-5. 2007
    ..Both drug categories are nephrotoxic as well as ototoxic. Aminoglycosides and cisplatin target the outer hair cells in the basal turn of the cochlea to cause high frequency ..
  65. pmc The prevalence of aminoglycoside-modifying enzyme genes (aac (6')-I, aac (6')-II, ant (2")-I, aph (3')-VI) in Pseudomonas aeruginosa
    Farzam Vaziri
    Department of Bacteriology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran
    Clinics (Sao Paulo) 66:1519-22. 2011
    ..aeruginosa) is one of the primary opportunistic pathogens responsible for nosocomial infections. Aminoglycosides are an import ant component of antipseudomonal chemotherapy...
  66. pmc The aminoglycoside resistance methyltransferases from the ArmA/Rmt family operate late in the 30S ribosomal biogenesis pathway
    Tamara Zarubica
    Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia 23298, USA
    RNA 17:346-55. 2011
    ..From our experiments, we conclude that ArmA is most active toward the 30S ribosomal subunits that are at or very near full maturity, but that it can also recognize more than one form of the 30S subunit...
  67. ncbi Rational use of aminoglycosides--review and recommendations by the Swedish Reference Group for Antibiotics (SRGA)
    Håkan Hanberger
    Department of Clinical and Experimental Medicine, Infectious Diseases, Faculty of Health Sciences, Linkoping University, Linkoping, Sweden
    Scand J Infect Dis 45:161-75. 2013
    ..against extended-spectrum beta-lactamase (ESBL)-producing and quinolone-resistant Escherichia coli than other aminoglycosides, making it a better option in cases of suspected infection caused by multidrug-resistant Enterobacteriaceae...
  68. ncbi Molecular genetics of Mycobacterium tuberculosis resistant to aminoglycosides and cyclic peptide capreomycin antibiotics in Korea
    Hum Nath Jnawali
    Department of Research and Development, Korean Institute of Tuberculosis, 168 5 Osongsangmyung4ro, Osongup, Cheongwongun, Chungbuk 363 954, Republic of Korea
    World J Microbiol Biotechnol 29:975-82. 2013
    b>Aminoglycosides are key drugs for the treatment of multidrug-resistant tuberculosis...
  69. pmc Side effects of aminoglycosides on the kidney, ear and balance in cystic fibrosis
    Andrew Prayle
    Child Health and Nottingham Respiratory Biomedical Research Unit, University of Nottingham, E Floor East Block, Queen s Medical Centre, Nottingham NG7 2UH, UK
    Thorax 65:654-8. 2010
    ..Observational studies suggest that the morbidity from side effects of aminoglycosides is disturbingly common, and that aggressive treatment may lead to more side effects...
  70. pmc Extracellular DNA shields against aminoglycosides in Pseudomonas aeruginosa biofilms
    Wen Chi Chiang
    Department of International Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
    Antimicrob Agents Chemother 57:2352-61. 2013
    ..In addition, it has recently been demonstrated that DNA binds positively charged antimicrobials such as aminoglycosides and antimicrobial peptides...
  71. pmc Novel polyoxins generated by heterologously expressing polyoxin biosynthetic gene cluster in the sanN inactivated mutant of Streptomyces ansochromogenes
    Jine Li
    State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
    Microb Cell Fact 11:135. 2012
    ..The gene cluster responsible for biosynthesis of polyoxins has been cloned and sequenced from Streptomyces cacaoi and tens of polyoxin analogs have been identified already...
  72. ncbi Once-daily dosing of aminoglycosides: review and recommendations for clinical practice
    C D Freeman
    Department of Medicine, University of Missouri Kansas City School of Medicine, 64108, USA
    J Antimicrob Chemother 39:677-86. 1997
    ..aminoglycoside regimens to optimize bacterial killing is justified by a pharmacodynamic principle of aminoglycosides, namely concentration-dependent killing, and by the partial attribution of the toxicity of aminoglycosides to ..
  73. pmc Crystal structure of trioxacarcin A covalently bound to DNA
    Roland Pfoh
    Lehrstuhl für Strukturchemie, Georg August Universitat, Tammannstr 4, 37077 Gottingen, Germany
    Nucleic Acids Res 36:3508-14. 2008
    ..An antibiotic-induced flipping-out of a single, nonterminal nucleobase from a DNA duplex was observed for the first time in a crystal structure...
  74. pmc RmtF, a new member of the aminoglycoside resistance 16S rRNA N7 G1405 methyltransferase family
    Marc Galimand
    Institut Pasteur, Unite des Agents Antibacteriens, Paris, France
    Antimicrob Agents Chemother 56:3960-2. 2012
    ..The deduced RmtF protein had 25 to 46% identity with members of the N7 G1405 family of aminoglycoside resistance 16S rRNA methyltransferases...
  75. pmc TRPA1-mediated accumulation of aminoglycosides in mouse cochlear outer hair cells
    Ruben S Stepanyan
    Department of Physiology, University of Kentucky, Lexington, KY 40536 0298, USA
    J Assoc Res Otolaryngol 12:729-40. 2011
    ..The exact route of entry of aminoglycosides into the hair cells in vivo is still unknown...
  76. pmc Nonsense-mediated mRNA decay affects nonsense transcript levels and governs response of cystic fibrosis patients to gentamicin
    Liat Linde
    Department of Genetics, Life Sciences Institute, The Hebrew University of Jerusalem, Jerusalem, Israel
    J Clin Invest 117:683-92. 2007
    b>Aminoglycosides can readthrough premature termination codons (PTCs), permitting translation of full-length proteins...
  77. ncbi Two-dimensional combinatorial screening identifies specific aminoglycoside-RNA internal loop partners
    Matthew D Disney
    Department of Chemistry, University at Buffalo, The State University of New York, and the New York State Center of Excellence in Bioinformatics and Life Sciences, 657 Natural Sciences Complex, Buffalo, New York 14260, USA
    J Am Chem Soc 130:11185-94. 2008
    ..RNAs that bound aminoglycosides were harvested from the array via gel excision...
  78. ncbi Status of high level aminoglycoside resistant Enterococcus faecium and Enterococcus faecalis in a rural hospital of central India
    D K Mendiratta
    Department of Microbiology, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Maharashtra, India
    Indian J Med Microbiol 26:369-71. 2008
    ..7%) were recovered, mostly from blood. Forty six percent showed HLAR. Multi drug resistance and concomitant resistance of HLAR strains to beta lactams were quite high. None showed beta lactamase activity or vancomycin resistance...
  79. pmc Aminoglycosides affect intracellular Salmonella enterica serovars typhimurium and virchow
    Ofir Menashe
    Department of Biotechnology and Food Engineering, Technion Israel Institute of Technology, Haifa 32000, Israel
    Antimicrob Agents Chemother 52:920-6. 2008
    The high antibacterial activity and selectivity of aminoglycosides and their low activity against intracellular bacteria associated with eukaryotic cells make them the antibiotics of choice for the elimination of extracellular bacteria ..
  80. ncbi Broad-spectrum peptide inhibitors of aminoglycoside antibiotic resistance enzymes
    David D Boehr
    Antimicrobial Research Centre, Department of Biochemistry, McMaster University, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada
    Chem Biol 10:189-96. 2003
    ..These peptides represent the first example of broad-spectrum inhibitors of aminoglycoside resistance enzymes...
  81. ncbi Effect of gemtuzumab ozogamicin on acute myeloid leukemia blast cells in vitro, as a single agent and combined with other cytotoxic cells
    K L Morris
    University Department of Clinical Haematology, Manchester Royal Infirmary, Manchester, UK
    Br J Haematol 135:509-12. 2006
    ..Combinations of GO with varying concentrations of cytarabine or etoposide were additive in inhibiting proliferation, reducing cell viability and increasing apoptosis...
  82. ncbi Evaluation of kasugamycin for fire blight management, effect on nontarget bacteria, and assessment of kasugamycin resistance potential in Erwinia amylovora
    Gayle C McGhee
    Department of Plant Pathology, Michigan State University, East Lansing, MI, USA
    Phytopathology 101:192-204. 2011
    ..amylovora. Our data confirm the importance of kasugamycin as an alternate antibiotic for fire blight management and lay the groundwork for the development and incorporation of resistance management strategies...
  83. ncbi Telavancin for the treatment of serious gram-positive infections, including hospital acquired pneumonia
    Ethan Rubinstein
    University of Manitoba, Faculty of Medicine, Section of Infectious Diseases, 543 745 Basic Medical Sciences Building, Winnipeg MB R3E 0J9, Canada
    Expert Opin Pharmacother 12:2737-50. 2011
    ..Despite the increasing prevalence of nosocomial pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA), approved treatment options for this pathogen are limited...
  84. ncbi Exogenously acquired 16S rRNA methyltransferases found in aminoglycoside-resistant pathogenic Gram-negative bacteria: an update
    Jun ichi Wachino
    Department of Bacteriology II, National Institute of Infectious Diseases, Tokyo, Japan
    Drug Resist Updat 15:133-48. 2012
    ..16S rRNA methyltransferase (16S-RMTase) genes responsible for a very high level of resistance against various aminoglycosides have been widely distributed among Enterobacteriaceae and glucose-nonfermentative microbes recovered from ..
  85. ncbi Discovery of non-carbohydrate inhibitors of aminoglycoside-modifying enzymes
    Karen T Welch
    Department of Biochemistry, Cellular and Molecular Biology and Center of Excellence for Structural Biology, University of Tennessee, Walters Life Sciences Building M407, Knoxville, TN 37996 0840, USA
    Bioorg Med Chem 13:6252-63. 2005
    Chemical modification and inactivation of aminoglycosides by many different enzymes expressed in pathogenic bacteria are the main mechanisms of bacterial resistance to these antibiotics...
  86. pmc Development of novel aminoglycoside (NB54) with reduced toxicity and enhanced suppression of disease-causing premature stop mutations
    Igor Nudelman
    The Edith and Joseph Fischer Enzyme Inhibitors Laboratory, Schulich Faculty of Chemistry, Technion Israel Institute of Technology, Haifa 32000, Israel
    J Med Chem 52:2836-45. 2009
    ..Comparative acute lethal toxicity in mice, cell toxicity, and the assessment of hair cell toxicity in cochlear explants further indicated that 2 exhibits far lower toxicity than that of gentamicin...
  87. ncbi Extracellular divalent cations modulate aminoglycoside-induced hair cell death in the zebrafish lateral line
    Allison B Coffin
    Virginia Merrill Bloedel Hearing Research Center, Department of Otolaryngology Head and Neck Surgery, University of Washington, Box 357923, Seattle, WA 98195, USA
    Hear Res 253:42-51. 2009
    ..These experiments lend further support to the hypothesis that aminoglycoside toxicity occurs via multiple pathways in a both a drug and time course-specific manner...
  88. ncbi Chromosomal mechanisms of aminoglycoside resistance in Pseudomonas aeruginosa isolates from cystic fibrosis patients
    S Islam
    Division of Clinical Microbiology F68, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
    Clin Microbiol Infect 15:60-6. 2009
    ..was found in 17/20 isolates collected in 1994 and 1997, and was correlated with decreased susceptibility to aminoglycosides. Alteration of the MexXY-OprM efflux system has been the main mechanism of resistance to aminoglycoside ..
  89. ncbi Molecular contacts between antibiotics and the 30S ribosomal particle
    Julia Wirmer
    Biologie Moléculaire et Cellulaire du CNRS, Universite Louis Pasteur, Strasbourg, France
    Methods Enzymol 415:180-202. 2006
    ..stacking (pactamycin) or form pseudo-base pairing interactions with ribosomal bases (paromomycin and related aminoglycosides)...
  90. ncbi Aminoglycoside-modifying enzymes
    G D Wright
    Antimicrobial Research Centre Department of Biochemistry McMaster University 1200 Main Street West, Hamilton, ON L8N 3Z5, Canada
    Curr Opin Microbiol 2:499-503. 1999
    ..Furthermore, the complete genome sequences for several bacteria have revealed many potential aminoglycoside-resistance elements...
  91. ncbi Aminoglycosides as potential pharmacogenetic agents in the treatment of Hailey-Hailey disease
    Richard Kellermayer
    J Invest Dermatol 126:229-31. 2006
  92. pmc Dissociation of antibacterial activity and aminoglycoside ototoxicity in the 4-monosubstituted 2-deoxystreptamine apramycin
    Tanja Matt
    Institut fur Medizinische Mikrobiologie, Universitat Zurich, 8006 Zurich, Switzerland
    Proc Natl Acad Sci U S A 109:10984-9. 2012
    b>Aminoglycosides are potent antibacterials, but therapy is compromised by substantial toxicity causing, in particular, irreversible hearing loss...
  93. pmc Intracellular mechanisms of aminoglycoside-induced cytotoxicity
    Takatoshi Karasawa
    Oregon Hearing Research Center, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA
    Integr Biol (Camb) 3:879-86. 2011
    ..Recent advances in molecular biology and biochemistry have begun to uncover the intracellular actions of aminoglycosides that lead to cytotoxicity...
  94. ncbi Coordination of export and glycosylation of landomycins in Streptomyces cyanogenus S136
    Iryna Ostash
    Department of Genetics and Biotechnology, Ivan Franko National University of L viv, L viv, Ukraine
    FEMS Microbiol Lett 285:195-202. 2008
    ..cyanogenus S136...
  95. pmc Functional hair cell mechanotransducer channels are required for aminoglycoside ototoxicity
    Abdelrahman Alharazneh
    Department of Otolaryngology Head and Neck Surgery, Stanford University, Stanford, California, United States of America
    PLoS ONE 6:e22347. 2011
    b>Aminoglycosides (AG) are commonly prescribed antibiotics with potent bactericidal activities. One main side effect is permanent sensorineural hearing loss, induced by selective inner ear sensory hair cell death...
  96. pmc Comparative susceptibilities to fidaxomicin (OPT-80) of isolates collected at baseline, recurrence, and failure from patients in two phase III trials of fidaxomicin against Clostridium difficile infection
    Ellie J C Goldstein
    2021 Santa Monica Blvd, Suite 740 East, Santa Monica, CA 90404
    Antimicrob Agents Chemother 55:5194-9. 2011
    ..There was no correlation between the MIC of a baseline clinical isolate and clinical outcome. MIC(90)s were generally low for fidaxomicin and vancomycin, but BI isolates had higher MICs than other REA group isolates...
  97. ncbi Aminoglycoside-induced ototoxicity
    Erol Selimoglu
    Inonu University, Department of Otorhinolaryngology, Malatya, Turkey
    Curr Pharm Des 13:119-26. 2007
    It has long been known that the major irreversible toxicity of aminoglycosides is ototoxicity...
  98. ncbi sanN encoding a dehydrogenase is essential for Nikkomycin biosynthesis in Streptomyces ansochromogenes
    Hong Bo Ling
    State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
    J Microbiol Biotechnol 18:397-403. 2008
    ..These data would facilitate us to understand the biosynthetic pathway of nikkomycins and to consider the combinatorial synthesis of novel antibiotic derivatives...
  99. ncbi Quantification of genes encoding resistance to aminoglycosides, beta-lactams and tetracyclines in wastewater environments by real-time PCR
    Stefan Borjesson
    Department of Clinical and Experimental Medicine, Linkoping University, Sweden
    Int J Environ Health Res 19:219-30. 2009
    ..PCR assays, based on the LUX-technique, were developed for quantification of genes mediating resistance to aminoglycosides [aac(6 ')-Ie + aph(2 ' ')], beta-lactams (mecA), and tetracyclines (tetA and tetB), for use in wastewater ..
  100. ncbi Phosphoryl transfer by aminoglycoside 3'-phosphotransferases and manifestation of antibiotic resistance
    Choonkeun Kim
    Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA
    Bioorg Chem 33:149-58. 2005
    ..This review article surveys the latest structural and mechanistic findings with these enzymes...
  101. pmc Read-through strategies for suppression of nonsense mutations in Duchenne/ Becker muscular dystrophy: aminoglycosides and ataluren (PTC124)
    Richard S Finkel
    Division of Neurology, The Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    J Child Neurol 25:1158-64. 2010
    ..Small-molecule drugs (aminoglycosides and ataluren [PTC124]) have been developed and are in clinical testing in patients with nonsense mutations ..

Research Grants63

  1. Optimization of Neoglycoside Antibiotics for Nosocomial Pathogens and Select Agen
    Arnold Louie; Fiscal Year: 2013
    ..b>Aminoglycosides have become less used because of increasing resistance and their potential to cause nephrotoxicity...
  2. CYCLE REGULATION IN THE SYMBIONT SINORHIZOBIUM MELILOTI
    KATHERINE ELISABETH GIBSON; Fiscal Year: 2011
    ..host-associated bacteria, and can thereby be applied towards development of novel targets for antimicrobial therapeutics at a time when resistance to [unreadable]-lactams and aminoglycosides is found in a variety of potent pathogens.
  3. Aminoglycoside potentiators for P. aeruginosa therapy
    Donald T Moir; Fiscal Year: 2013
    ..While P. aeruginosa exhibits an alarming variety of intrinsic drug resistances, aminoglycosides (AMGs) such as tobramycin and amikacin, are still effective in treating diseases caused by this pathogen, ..
  4. PROTECTION FROM AMINOGLYCOSIDE OTOTOXICITY
    Jochen Schacht; Fiscal Year: 2013
    Summary: Aminoglycosides are indispensable antibiotics commonly used worldwide and a primary cause of preventable hearing loss...
  5. Intercellular trafficking of labeled aminoglycosides in living hair cells
    Dale Warren Hailey; Fiscal Year: 2013
    ..This project focuses on hair cell death caused by exposure to a family of ototoxic antibiotics-the aminoglycosides. Aminoglycosides specifically kill hair cells and cells of the proximal tubule of the kidney, in addition to ..
  6. Aminoglycoside microbicides restore natural expression of anti-HIV-1 retrocyclins
    Alexander M Cole; Fiscal Year: 2010
    ..In eukaryotes, aminoglycosides can suppress premature termination codons through the incorporation of an amino acid in its place...
  7. Aminoglycoside microbicides restore natural expression of anti-HIV-1 retrocyclins
    ALEXANDER MICHAEL COLE; Fiscal Year: 2013
    ..In eukaryotes, aminoglycosides can suppress premature termination codons through the incorporation of an amino acid in its place...
  8. Firing up new treatments against Mycobacterium ulcerans disease (Buruli ulcer)
    Jacques H Grosset; Fiscal Year: 2013
    ..Because all drugs tested to date, with the exception of aminoglycosides and rifampin, have only bacteriostatic activity against M...
  9. Determining how aminoglycoside-induced hair cell death is blocked
    Dale Warren Hailey; Fiscal Year: 2010
    ..These include the aminoglycoside antibiotics. Aminoglycosides are used in this country to treat chronic life threatening conditions, and in underdeveloped countries often ..
  10. Mechanistic Basis Underlying Protein Repair of CFTR Nonsense Mutations
    STEVEN MARK ROWE; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): Suppression of premature termination codons (PTCs) with aminoglycosides and other agents has the potential to treat an underlying cause of cystic fibrosis (CF) and other genetic diseases including ..
  11. Identification of gentamicin-binding proteins in the inner ear
    Takatoshi Karasawa; Fiscal Year: 2010
    Aminoglycoside antibiotics like gentamicin are essential for battling life-threatening bacterial infections. Aminoglycosides also cause permanent deafness/balance disorders and nephrotoxicity in more than 120,000 individuals each year ..
  12. Pseudomonas aeruginosa Adaptation During Early CF Airway Infection and Treatment
    Lucas R Hoffman; Fiscal Year: 2012
    ..increased resistance to the three classes of antibiotic used most often in CF therapy: [unreadable]lactams, aminoglycosides, and fluoroquinolones...
  13. Ameliorating systemic gentamicin uptake by sensory hair cells
    PETER STEPHEN STEYGER; Fiscal Year: 2013
    ..The goal of this proposal is to identify the molecular mechanisms that traffic aminoglycosides across the blood-labyrinth barrier into the cochlear fluids and sensory hair cells to induce cytotoxicity and ..
  14. Development of novel proteins synthesis inhibitors for MDR tuberculosis
    RICHARD EDWARD LEE; Fiscal Year: 2013
    ..profile;targets a ribosomal binding site highly conserved across bacterial pathogens, but separate from other aminoglycosides;is potent in cell free assays;is structurally tractable, allowing for advanced synthetic modification using ..
  15. Disinfectant-resistant mycobacteria
    Mary Jackson; Fiscal Year: 2013
    ..massiliense clinical isolate, the epidemic M. massiliense isolates from Brazil display unusual resistance to aminoglycosides and much increased pathogenicity in mice. We have assembled a collection of GTA-resistant isolates of M...
  16. p53 and aminoglycoside-induced hair cell death in the zebrafish lateral line
    Allison B Coffin; Fiscal Year: 2013
    ..Our previous research has demonstrated that the closely related aminoglycosides neomycin and gentamicin damage hair cells via at least two distinct and partially overlapping cell death ..
  17. Cochlear trafficking and hair cell uptake of aminoglycosides
    PETER STEPHEN STEYGER; Fiscal Year: 2013
    ..The long-term goal of this research is to prevent the cochlear uptake of aminoglycosides and subsequent ototoxicity, thus preserving life-long auditory function...
  18. Aminoglycoside-Enabled Elucidation of Persister Metabolism
    Mark P Brynildsen; Fiscal Year: 2013
    ..that persisters can catabolize carbon sources, remain non-replicative, and yet become susceptible to aminoglycosides. Here we propose to harness this phenomenon to chart the metabolic capabilities of persisters...
  19. Tuning aminoglycosides for treatment of genetic diseases
    Timor Baasov; Fiscal Year: 2013
    ..The main objective of this research is to develop novel aminoglycosides that will have efficient termination suppression activity, and at the same time will have reduced toxicity ..
  20. Epidemiology of Community-Associated, ESBL-Producing Escherichia coli
    Yohei Doi; Fiscal Year: 2010
    ..These organisms are not only resistant to most beta-lactams but also fluoroquinolones and aminoglycosides. ESBL producers have typically been regarded as a problem confined to hospitals...
  21. Retrocyclins: Circular Defensins Active Against HIV-1
    Alexander M Cole; Fiscal Year: 2010
    ..IFN-beta is an essential factor that enhances the expression of retrocyclin mRNA, and c) agents such as aminoglycosides, which can suppress the premature termination codon in retrocyclin mRNA, will enable human cells to express ..
  22. BIOCHEMISTRY OF BACTERIAL CELL MEMBRANES
    Hiroshi Nikaido; Fiscal Year: 2013
    ..pump of Escherichia coli, which pumps out most of the commonly used antibiotics, with the sole exception of aminoglycosides. It will try to elucidate the path the drug molecule follows inside the large AcrB transporter, and the ..
  23. Non-Invasive Optical Determination of GFR
    Bruce A Molitoris; Fiscal Year: 2010
    ..extend these observations into animal models of AKI including ischemia, sepsis, and nephrotoxins, such as aminoglycosides and radiocontrast agents...
  24. MTRNR1 Aminoglycoside Ototoxicity Outcomes and Parental Perceptions of Testing
    Tracy L McGregor; Fiscal Year: 2013
    ..The first aim addresses patients with MTRNR1 mutations who have been treated with aminoglycosides and compares their incidence of hearing loss to those without MTRNR1 mutations who have been treated with ..
  25. smFRET Investigation of Aminoglycoside-induced Ototoxicity
    Michael R Wasserman; Fiscal Year: 2013
    ..b>Aminoglycosides preferentially bind to the near-universally conserved decoding site of the bacterial ribosome, where proper ..
  26. A novel assay for RNA targeted drugs
    DEV PRIYA ARYA; Fiscal Year: 2011
    ..This project is designed to synthesize and characterize a novel class of fluorescently-labeled aminoglycosides that exhibit a dramatic change in fluorescence upon RNA binding...
  27. Chemoenzymatic studies of aminoglycoside-resistance enzymes towards new drugs
    Sylvie Garneau-Tsodikova; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Aminoglycosides are broad-spectrum antibiotics used for treatment of serious bacterial infections, including the deadly tuberculosis and those accompanying AIDS, cystic fibrosis, and cancer...
  28. NUCLEIC ACID PROBES OF RIBOSOMAL STRUCTURE AND FUNCTION
    BARRY COOPERMAN; Fiscal Year: 2003
    ..in current clinical use, such as tetracycline, erythromycin and other macrolides, neomycin and other aminoglycosides, and chloramphenicol target ribosomes as their sites of action...
  29. Inhaled Aminoglycoside Formulafor Plague and Tularemia
    James Talton; Fiscal Year: 2005
    In this proposal, Nanotherapeutics proposes to investigate inhaled dry-powder formulations of two aminoglycosides, streptomycin and gentamicin, for post-exposure treatment of aerosol exposure of the Category A bioterrorism agents ..
  30. Enhancement of antimicrobics by electrical current
    Robin Patel; Fiscal Year: 2007
    ..In vitro experiments have shown that electric current can enhance the activity of aminoglycosides, quinolones or oxytetracycline against bacteria in biofilms; this has been termed the 'bioelectric ..
  31. Hygromycin A: Activity, Biosynthesis, Export, Resistance and Regulation
    Kevin A Reynolds; Fiscal Year: 2013
    ..important classes of antibiotics, including macrolides (azithromycin, telithromycin), tetracyclines, aminoglycosides (gentamycin), and more recently oxazolidinones (linezolid) target the bacterial ribosome, which is essential ..
  32. Aminoglycoside Resistance in Bacteria
    Sergei Vakulenko; Fiscal Year: 2013
    ..aminoglycoside antibiotics would provide an important guidance for the future utility of clinically important aminoglycosides. Ultimately, such knowledge will provide the basis for the design of new aminoglycoside antibiotics and ..
  33. Functional similarities in renal and cochlear epithelia
    PETER STEYGER; Fiscal Year: 2004
    b>Aminoglycosides are clinically essential for treating life-threatening Gram-negative bacterial infections, e.g., meningitis, and in preventing infection in burns and premature babies...
  34. Dealing with Antibiotic Resistance: Antisense Technology
    Marcelo E Tolmasky; Fiscal Year: 2013
    ..acetyltransferase among gram-negative pathogens, which mediates resistance to amikacin (Ak) and other aminoglycosides. These antibiotics are an important component of the armamentarium against serious infections caused by ..
  35. Developing Non-Ototoxic Aminoglycosides
    Anthony J Ricci; Fiscal Year: 2012
    ..The goal of this proposal is to develop novel non-ototoxic aminoglycosides. Our team has unique insights into the biophysical properties of the mechanically gated channels and can use ..
  36. Aminoglycoside Antivirals to Combat Arenaviruses
    JUAN DE LA TORRE; Fiscal Year: 2004
    ..Aim 2 will assess the antiviral activity of binder molecules (Aim 1). Selected aminoglycosides will be tested for: (i) their effects on RNA synthesis mediated by the LCMV polymerase using our LCMV ..
  37. ELECTRON TRANSPORT VARIANTS IN STAPHYLOCOCCAL DISEASE
    Richard Proctor; Fiscal Year: 2001
    ..Uptake of many positively charged antibiotics (aminoglycosides, many lantibiotics, cationic peptides) require intact electron transport to generate an electrochemical ..
  38. CONTRIBUTION OF LPS TO EXP ENTEROCOCCAL SEPSIS
    Christopher Papasian; Fiscal Year: 2000
    ..a propensity for rapid development of resistance to broad-spectrum antibacterial agents including vancomycin, aminoglycosides, and extended spectrum beta-lactam antimicrobial agents...
  39. Intra-species regulatory functions of fsr
    Satish Pillai; Fiscal Year: 2004
    ..faecalis to beta-lactam antibiotics, vancomycin, and aminoglycosides. The applicant is an Infectious Diseases fellow at Beth Israel Deaconess Medical Center, and will conduct ..
  40. IRIS PIGMENTATION, MELANINS AND OCULAR DRUG EFFECTS
    POPAT PATIL; Fiscal Year: 1980
    ..Ototoxicity of many antibiotics, aminoglycosides like neomycin, kanamycin and gentamicin, is at least in part equated with drug binding by the inner ear ..
  41. Calcium Sensing Receptor in Human Airway Epithelium
    PHILLIP LAMBERTY; Fiscal Year: 2003
    ..agonists other than calcium include other polycations (Mg2+, Gd3+), polyamines (spermine, neomycin), and aminoglycosides. It has been described to regulate cellular processes in cell types and tissues not associated with calcium ..
  42. Molecular studies of hair cell death
    Alan Cheng; Fiscal Year: 2001
    ..Aging, exposure to noise and therapeutic drugs such as aminoglycosides are all known direct causes of hair cell death...
  43. Differences in neomycin and gentamicin toxicity in the zebrafish lateral line
    ALLISON COFFIN; Fiscal Year: 2009
    ..Preliminary data in our lab suggests that different aminoglycosides may act via partially overlapping cell death pathways but that different antibiotics may also activate unique ..
  44. ACQUIRED HEARING LOSS
    Richard Salvi; Fiscal Year: 2003
    ..lateral and medial olivocochlear efferent fibers on hair cell loss and hearing loss induced by carboplatin, aminoglycosides, kainic acid and acoustic over-stimulation...
  45. ACTIVE-SITE CHARACTERIZATION FOR APH(3')-II
    Michael Perlin; Fiscal Year: 1992
    ..alteration the genes for these enzymes provide a reservoir from which bacterial resistance to newly designed aminoglycosides might emerge...
  46. Undermining aminoglycoside resistance in Pseudomonas aeruginosa
    Colin Manoil; Fiscal Year: 2009
    ..which the regulator helps counteract intracellular pH/proton motive force stress caused by active efflux of aminoglycosides. Finally, strains suitable for screening small molecule libraries for specific inhibitors of EnvZ-OmpR will ..
  47. ENDOGENOUS MODULATION OF OTO- AND NEPHROTOXICITY
    Douglas Hoffman; Fiscal Year: 1992
    ..b>Aminoglycosides and cisplatin can deplete GSH levels, particularly in the kidney, which has a limited capacity for GSH ..
  48. Knock-In Model for Inner Ear Hair Cell Regeneration
    KATE BARALD; Fiscal Year: 2006
    ..By using focal noise exposure or precisely dosed and delivered aminoglycosides, we can vary the site and extent of the lesions, and determine the degree to which repair, regeneration and/..
  49. AMINOGLYCOSIDE OTOTOXICITY DETERMINANTS
    WILLARD FEE; Fiscal Year: 1980
    ..groups by computer analysis in an effort to make comparative evaluation of the toxicities of the different aminoglycosides under similar clinical conditions...
  50. Gentamicin Trial in Duchenne and Limb Girdle Dystrophies
    Jerry Mendell; Fiscal Year: 2004
    ..One group of 14-day subjects will have DMD with frameshift mutations. Despite commonly held dogma that aminoglycosides have no effect on this mutation-type, it is important to establish as effect by testing to see if CK drops...
  51. AMINOGLYCOSIDE/RNA INTERACTIONS AND CORNEAL INFECTIONS
    Robert Rando; Fiscal Year: 2003
    ..to gaining an understanding of the rules by which certain classes of naturally occurring RNA antagonists, the aminoglycosides, are recognized by specific RNA molecules...
  52. TAS::75 0885::TAS EFFICACY OF ORAL AMINOGLYCOSIDE-COCHLEATE FORMULATIONS
    BONITZ SUSAN; Fiscal Year: 2010
    The long term goal of this project is to prepare cochleate formulations of aminoglycosides that will demonstrate efficacious oral bioavailability and reduced toxicity in animal models of Mycobacterium avium.
  53. AMINOGLYCOSIDE 3 PHOSPHOTRANSFERASES
    Shahriar Mobashery; Fiscal Year: 1999
    ..antibacterial by either their binding to the bacterial ribosome (the normal mechanism of bacte rial death by aminoglycosides) or by in vivo depletion of the nucleotide triphosphate pool in the cytoplasm...
  54. TAS::75 0885::TAS EFFICACY OF ORAL AMINOGLYCOSIDE-COCHLEATE FORMULATIONS
    Moses Sing Sum Chow; Fiscal Year: 2010
    ..that could allow for therapeutically effective oral formulation of highly water soluble drugs, such as the aminoglycosides. The phase I objective is to test the feasibility of using a specific nanotechnology to develop a ..
  55. Aminoglycoside induced restoration of wild type APC
    Rina Rosin Arbesfeld; Fiscal Year: 2006
    ..The aim of this application is to investigate the effect of aminoglycosides on the pre-mature stop codons in the APC gene and to induce expression of full length APC in colon cancer ..
  56. MULTIFACTORIAL COMPARISON--AMINOGLYCOSIDE NEPHROTOXICITY
    GIRARD HOTTENDORF; Fiscal Year: 1993
    ..Extensive studies in rats indicate differences in the nephrotoxic potential of individual aminoglycosides, but these differences are difficult to assess in seriously ill patients...
  57. Molecular Basis for Antibiotic Specificity
    Malvika Kaul; Fiscal Year: 2007
    b>Aminoglycosides are drugs used in the treatment of several bacterial infections that are potential agents of bioterrorism...
  58. CELLULAR MECHANISMS OF OTOTOXICITY
    Eri Hashino; Fiscal Year: 2003
    ..include: (l) Determination of the plasma membrane assembly involved in receptor-mediated endocytosis of aminoglycosides; (2) Evaluation of the role of microtubules in lysosomal targeting of aminoglycosides; (3) Evaluation of the ..
  59. Rational Design of Antibiotics Targeted at the Ribosome
    Daniel Wall; Fiscal Year: 2005
    ..The ribosomal A-site constitutes a prime target for antibiotics, validated by the naturally occurring aminoglycosides and a novel series of chemically unrelated antibacterials that we have discovered recently...
  60. Combinatorial Carbohydrate Libraries for Drug Discovery
    Richard Griffey; Fiscal Year: 2001
    ..Five hundred new aminoglycosides will be prepared using solution and solid-phase methods...
  61. Enhancing RNA binding selectivity of guanidinoglycosides
    Kenneth Blount; Fiscal Year: 2005
    ..During the first year, the development of parallel binding assays for two diverse RNA targets known to bind aminoglycosides will be developed...
  62. AMINOGLYCOSIDE NEPHROTOXICITY AND CELLULAR TRANSPORT
    MARY SENS; Fiscal Year: 1992
    ..is postulated that these cells are not reliant on sodium-dependent processes and, thus, are resistant to the aminoglycosides. Preliminary data is presented to support this hypothesis...
  63. Using Genomics to Identify Antibiotic Sensitivity Genes
    Ryan Gill; Fiscal Year: 2004
    ..be done with a plasmid either expressing the enzyme 6"-N-aminoglycoside acetyltransferase7, which modifies aminoglycosides or expressing the phoP gene, which reduces bacterial permeability to aminoglycosideds...