polymyxins

Summary

Summary: Basic polypeptide antibiotic group obtained from Bacillus polymyxa. They affect the cell membrane by detergent action and may cause neuromuscular and kidney damage. At least eleven different members of the polymyxin group have been identified, each designated by a letter.

Top Publications

  1. ncbi Clinical Microbiology and Infectious Diseases (ECCMID)--18th European Congress. Drug resistance among Gram-negative and Gram-positive bacteria
    Matthew E Falagas
    Alfa Institute of Biomedical Sciences, 9 Neapoleos Street, 151 23 Marousi, Athens, Greece
    IDrugs 11:409-11. 2008
  2. pmc Toxicity of polymyxins: a systematic review of the evidence from old and recent studies
    Matthew E Falagas
    Alfa Institute of Biomedical Sciences, Athens, Greece
    Crit Care 10:R27. 2006
  3. ncbi Polymyxins: pharmacology, pharmacokinetics, pharmacodynamics, and clinical applications
    Elizabeth D Hermsen
    Experimental and Clinical Pharmacology, University of Minnesota College of Pharmacy, Weaver Densford Hall 7 170, 308 Harvard Street SE, Minneapolis, MN 55455, USA
    Infect Dis Clin North Am 17:545-62. 2003
  4. ncbi An inner membrane enzyme in Salmonella and Escherichia coli that transfers 4-amino-4-deoxy-L-arabinose to lipid A: induction on polymyxin-resistant mutants and role of a novel lipid-linked donor
    M S Trent
    Department of Biochemistry, Duke NMR Spectroscopy Center, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 276:43122-31. 2001
  5. ncbi Origin of lipid A species modified with 4-amino-4-deoxy-L-arabinose in polymyxin-resistant mutants of Escherichia coli. An aminotransferase (ArnB) that generates UDP-4-deoxyl-L-arabinose
    Steven D Breazeale
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 278:24731-9. 2003
  6. pmc A two-component regulatory system interconnects resistance to polymyxins, aminoglycosides, fluoroquinolones, and β-lactams in Pseudomonas aeruginosa
    Cédric Muller
    Laboratoire de Bacteriologie, Faculte de Medecine, Universite de Franche Comte, 25030 Besancon, France
    Antimicrob Agents Chemother 55:1211-21. 2011
  7. pmc Polymyxins revisited
    David Landman
    Division of Infectious Diseases, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA
    Clin Microbiol Rev 21:449-65. 2008
  8. ncbi PmrA-PmrB-regulated genes necessary for 4-aminoarabinose lipid A modification and polymyxin resistance
    J S Gunn
    University of Washington, Department of Medicine, Seattle 98195, USA
    Mol Microbiol 27:1171-82. 1998
  9. ncbi Resistance to polymyxins: Mechanisms, frequency and treatment options
    Matthew E Falagas
    Alfa Institute of Biomedical Sciences AIBS, Athens, Greece
    Drug Resist Updat 13:132-8. 2010
  10. ncbi Polymyxins: Antimicrobial susceptibility concerns and therapeutic options
    V Balaji
    Department of Clinical Microbiology, Christian Medical College, Vellore 632 004, Tamil Nadu, India
    Indian J Med Microbiol 29:230-42. 2011

Detail Information

Publications194 found, 100 shown here

  1. ncbi Clinical Microbiology and Infectious Diseases (ECCMID)--18th European Congress. Drug resistance among Gram-negative and Gram-positive bacteria
    Matthew E Falagas
    Alfa Institute of Biomedical Sciences, 9 Neapoleos Street, 151 23 Marousi, Athens, Greece
    IDrugs 11:409-11. 2008
  2. pmc Toxicity of polymyxins: a systematic review of the evidence from old and recent studies
    Matthew E Falagas
    Alfa Institute of Biomedical Sciences, Athens, Greece
    Crit Care 10:R27. 2006
    ..causing severe infections and the shortage of new antibiotics to combat them has led to the re-evaluation of polymyxins. These antibiotics were discovered from different species of Bacillus polymyxa in 1947; only two of them, ..
  3. ncbi Polymyxins: pharmacology, pharmacokinetics, pharmacodynamics, and clinical applications
    Elizabeth D Hermsen
    Experimental and Clinical Pharmacology, University of Minnesota College of Pharmacy, Weaver Densford Hall 7 170, 308 Harvard Street SE, Minneapolis, MN 55455, USA
    Infect Dis Clin North Am 17:545-62. 2003
    Although the polymyxins seem attractive because of their unique structure and mechanism of action, relatively little is known about this group of antibiotics...
  4. ncbi An inner membrane enzyme in Salmonella and Escherichia coli that transfers 4-amino-4-deoxy-L-arabinose to lipid A: induction on polymyxin-resistant mutants and role of a novel lipid-linked donor
    M S Trent
    Department of Biochemistry, Duke NMR Spectroscopy Center, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 276:43122-31. 2001
    ..R. H. (2001) J. Biol. Chem. 276, 43132-43144), ArnT utilizes the novel lipid undecaprenyl phosphate-alpha-l-Ara4N as its sugar donor, suggesting that l-Ara4N transfer to lipid A occurs on the periplasmic side of the inner membrane...
  5. ncbi Origin of lipid A species modified with 4-amino-4-deoxy-L-arabinose in polymyxin-resistant mutants of Escherichia coli. An aminotransferase (ArnB) that generates UDP-4-deoxyl-L-arabinose
    Steven D Breazeale
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 278:24731-9. 2003
    ..1). ArnB is a member of a very large family of aminotransferases, but closely related ArnB orthologs are present only in those bacteria capable of synthesizing lipid A species modified with the l-Ara4N moiety...
  6. pmc A two-component regulatory system interconnects resistance to polymyxins, aminoglycosides, fluoroquinolones, and β-lactams in Pseudomonas aeruginosa
    Cédric Muller
    Laboratoire de Bacteriologie, Faculte de Medecine, Universite de Franche Comte, 25030 Besancon, France
    Antimicrob Agents Chemother 55:1211-21. 2011
    ....
  7. pmc Polymyxins revisited
    David Landman
    Division of Infectious Diseases, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA
    Clin Microbiol Rev 21:449-65. 2008
    The global emergence of multidrug-resistant gram-negative bacilli has spurred a renewed interest in polymyxins. Once discarded due to concerns regarding nephrotoxicity and neurotoxicity, polymyxins now hold an important role in the ..
  8. ncbi PmrA-PmrB-regulated genes necessary for 4-aminoarabinose lipid A modification and polymyxin resistance
    J S Gunn
    University of Washington, Department of Medicine, Seattle 98195, USA
    Mol Microbiol 27:1171-82. 1998
    ....
  9. ncbi Resistance to polymyxins: Mechanisms, frequency and treatment options
    Matthew E Falagas
    Alfa Institute of Biomedical Sciences AIBS, Athens, Greece
    Drug Resist Updat 13:132-8. 2010
    b>Polymyxins act by binding to lipid A moiety of the bacterial lipopolysaccharide and subsequently disintegrating the bacterial membranes...
  10. ncbi Polymyxins: Antimicrobial susceptibility concerns and therapeutic options
    V Balaji
    Department of Clinical Microbiology, Christian Medical College, Vellore 632 004, Tamil Nadu, India
    Indian J Med Microbiol 29:230-42. 2011
    ..Not as a favour or at request, but as a responsibility...
  11. pmc Pharmacology of polymyxins: new insights into an 'old' class of antibiotics
    Tony Velkov
    Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, 381 Royal Parade Parkville 3052, Victoria, Australia
    Future Microbiol 8:711-24. 2013
    ..Before new antibiotics become available, we must optimize the clinical use of polymyxins through the application of pharmacokinetic/pharmacodynamic principles, thereby minimizing the development of ..
  12. pmc Structure-activity relationships for the binding of polymyxins with human α-1-acid glycoprotein
    Mohammad A K Azad
    Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Parkville, Victoria 3052, Australia
    Biochem Pharmacol 84:278-91. 2012
    ..interactions coupled to desolvation events and conformational changes are the primary driving force for polymyxins binding to AGP...
  13. ncbi A novel role for protein-tyrosine kinase Etk from Escherichia coli K-12 related to polymyxin resistance
    Soline Lacour
    Institute of Biology and Chemistry of Proteins, University of Lyon CNRS, 7, passage du Vercors 69367 Lyon Cedex 07, France
    Res Microbiol 157:637-41. 2006
    ..This newly found specific function of Etk reinforces the concept that protein-tyrosine kinases are involved in distinct facets of bacterial physiology...
  14. ncbi Novel derivatives of polymyxins
    Martti Vaara
    Division of Clinical Microbiology, Helsinki University Hospital, FI 00029 HUSLAB, Helsinki, Finland
    J Antimicrob Chemother 68:1213-9. 2013
    ..This article reviews recent attempts to develop novel derivatives of polymyxins that exhibit less toxicity and greater potency than the existing drugs...
  15. ncbi A signal transduction system that responds to extracellular iron
    M M Wösten
    Department of Molecular Microbiology, Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Cell 103:113-25. 2000
    ..A pmrA mutant was hypersensitive to killing by iron but displayed wild-type resistance to a variety of oxidants, suggesting PmrA/PmrB controls a novel pathway mediating the avoidance of iron toxicity...
  16. ncbi Polymyxins and their novel derivatives
    Martti Vaara
    Northern Antibiotics Ltd, Eskolantie 1, POB 72, FI 00720 Helsinki, Finland Division of Clinical Microbiology, Helsinki University Hospital, Haartmaninkatu 3, POB 30, FI 00029 HUSLAB, Helsinki, Finland
    Curr Opin Microbiol 13:574-81. 2010
    ..There are no novel classes of agents in clinical development for the treatment of Gram-negative infections. Polymyxins (polymyxin B and colistin) were abandoned in the seventies but are now back in the therapy as the last resort...
  17. pmc Spontaneous pmrA mutants of Salmonella typhimurium LT2 define a new two-component regulatory system with a possible role in virulence
    K L Roland
    Department of Microbiology and Immunology, Emory University, Atlanta, Georgia 30322
    J Bacteriol 175:4154-64. 1993
    ..We therefore designate ORF2 PmrA and ORF3 PmrB. The function of ORF1 is unknown...
  18. ncbi Identification and functional analysis of Salmonella enterica serovar Typhimurium PmrA-regulated genes
    Rita Tamayo
    Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MC 7758, San Antonio, TX 78229 3900, USA
    FEMS Immunol Med Microbiol 43:249-58. 2005
    ..A more complete definition of the PmrA-PmrB regulon will provide a better understanding of its role in host and non-host environments...
  19. pmc A small protein that mediates the activation of a two-component system by another two-component system
    L F Kox
    Department of Molecular Microbiology, Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, MO 63110 1093, USA
    EMBO J 19:1861-72. 2000
    ..A pmrD mutant is sensitive to polymyxin if grown in low magnesium, but resistant if grown in high iron. The PmrD protein controls the activity of the PmrA-PmrB system at a post-transcriptional level...
  20. pmc The use of intravenous and aerosolized polymyxins for the treatment of infections in critically ill patients: a review of the recent literature
    Matthew E Falagas
    Alfa Institute of Biomedical Sciences, Athens, Greece
    Clin Med Res 4:138-46. 2006
    Intravenous and aerosolized polymyxins are being used increasingly, especially in the critical care setting, for treating patients with infections due to multidrug-resistant Gram-negative bacteria, mainly Acinetobacter baumannii and ..
  21. ncbi Polymyxins: old antibiotics are back
    Matthew E Falagas
    Alfa Institute of Biomedical Sciences AIBS, Athens, Greece
    Lancet 367:633-4. 2006
  22. pmc Regulation of polymyxin resistance and adaptation to low-Mg2+ environments
    E A Groisman
    Howard Hughes Medical Institute and Department of Molecular Microbiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Bacteriol 179:7040-5. 1997
    ..We propose that the LPS is a Mg2+ reservoir and that the PmrA-controlled LPS modifications neutralize surface negative charges when Mg2+ is transported into the cytoplasm during growth in Mg2+-limited environments...
  23. ncbi Polymyxins: a review of the current status including recent developments
    Andrea L Kwa
    Department of Pharmacy, Singapore General Hospital, Singapore
    Ann Acad Med Singapore 37:870-83. 2008
    b>Polymyxins have become the drug of choice for treatment of multidrug-resistant gram-negative bacilli infections in Singapore, simply because these pathogens are only susceptible to either aminoglycosides and polymyxins, or polymyxins only...
  24. ncbi Accumulation of a polyisoprene-linked amino sugar in polymyxin-resistant Salmonella typhimurium and Escherichia coli: structural characterization and transfer to lipid A in the periplasm
    M S Trent
    Department of Biochemistry and the Duke NMR Spectroscopy Center, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 276:43132-44. 2001
    ....
  25. ncbi Gramicidin S and polymyxins: the revival of cationic cyclic peptide antibiotics
    Tatsushi Mogi
    Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Bunkyo ku, Tokyo 113 0033, Japan
    Cell Mol Life Sci 66:3821-6. 2009
    Gramicidin S and polymyxins are small cationic cyclic peptides and act as potent antibiotics against Gram-negative and Gram-positive bacteria by perturbing integrity of the bacterial membranes...
  26. ncbi Current use for old antibacterial agents: polymyxins, rifampin, and aminoglycosides
    Donald Kaye
    Department of Medicine, Drexel University, College of Medicine, 3300 Henry Avenue, Philadelphia, PA 19129, USA
    Infect Dis Clin North Am 18:669-89, x. 2004
    ..These are the polymyxins, rifampin, and the aminoglycosides.
  27. ncbi A formyltransferase required for polymyxin resistance in Escherichia coli and the modification of lipid A with 4-Amino-4-deoxy-L-arabinose. Identification and function oF UDP-4-deoxy-4-formamido-L-arabinose
    Steven D Breazeale
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 280:14154-67. 2005
    ..Because the L-Ara4N unit attached to lipid A is not derivatized with a formyl group, we postulate the existence of a deformylase, acting later in the pathway...
  28. pmc Drugs of last resort? The use of polymyxins and tigecycline at US Veterans Affairs medical centers, 2005-2010
    Benedikt Huttner
    VA Salt Lake City Health Care System and University of Utah, Salt Lake City, Utah, United States of America
    PLoS ONE 7:e36649. 2012
    ..b>Polymyxins and tigecycline are among the few antibiotics available to treat infections with these bacteria but little is ..
  29. ncbi Intraventricular or intrathecal use of polymyxins in patients with Gram-negative meningitis: a systematic review of the available evidence
    Matthew E Falagas
    Alfa Institute of Biomedical Sciences AIBS, 9 Neapoleos Street, 151 23 Marousi, Athens, Greece
    Int J Antimicrob Agents 29:9-25. 2007
    Several reports have described the use of polymyxins by the intraventricular or intrathecal route for multidrug-resistant Gram-negative meningitis...
  30. ncbi Current use for old antibacterial agents: polymyxins, rifamycins, and aminoglycosides
    Luke F Chen
    Department of Medicine, Division of Infectious Diseases and International Health, Duke University Medical Center, Box 102359, Hanes House, Durham, NC 27710, USA
    Infect Dis Clin North Am 23:1053-75, x. 2009
    ..The polymyxins are reserved for gram-negative bacilli that are resistant to virtually all other classes of drugs...
  31. pmc Acid pH activation of the PmrA/PmrB two-component regulatory system of Salmonella enterica
    J Christian Perez
    Program in Molecular Genetics, Howard Hughes Medical Institute, Washington University School of Medicine, Campus Box 8230, 660 S Euclid Ave, St Louis, MO 63110, USA
    Mol Microbiol 63:283-93. 2007
    ..7. Our results suggest that protonation of the PmrB periplasmic histidine and/or of the glutamic acid residues activate the PmrA protein, and that mild acid promotes cellular changes resulting in polymyxin B resistance...
  32. pmc The lipid A 1-phosphatase of Helicobacter pylori is required for resistance to the antimicrobial peptide polymyxin
    An X Tran
    Department of Microbiology, J H Quillen College of Medicine, Johnson City, TN 37614, USA
    J Bacteriol 188:4531-41. 2006
    ..In conclusion, we have characterized the first gram-negative LpxE-deficient mutant and have shown the importance of modifying the 1 position of H. pylori lipid A for resistance to polymyxin...
  33. ncbi When to include polymyxins in the empirical antibiotic regimen in critically ill patients with fever? A decision analysis approach
    Matthew E Falagas
    Alfa Institute of Biomedical Sciences, Athens, Greece
    Shock 27:605-9. 2007
    We sought to approach a practical question: Should polymyxins be used in the initial empirical antibiotic regimen in the intensive care unit (ICU) patient with fever that is thought to be due to infection? By retrieving data from the ..
  34. pmc Crystal structure and mechanism of the Escherichia coli ArnA (PmrI) transformylase domain. An enzyme for lipid A modification with 4-amino-4-deoxy-L-arabinose and polymyxin resistance
    Petia Z Gatzeva-Topalova
    Department of Chemistry and Biochemistry, University of Colorado at Boulder, 80309, USA
    Biochemistry 44:5328-38. 2005
    ..We also propose a mechanism for the transformylation reaction catalyzed by ArnA involving residues N(102), H(104), and D(140). Supporting this hypothesis, point mutation of any of these residues abolishes activity...
  35. pmc Risk factors for isolation of strains susceptible only to polymyxin among patients with Pseudomonas aeruginosa bacteremia
    Matthew E Falagas
    Alfa Institute of Biomedical Sciences, Athens, Greece
    Antimicrob Agents Chemother 50:2541-3. 2006
    ..to polymyxin from blood by comparing data between 16 patients with blood isolates that were susceptible only to polymyxins and 40 patients with blood isolates that were susceptible to carbapenems...
  36. pmc Induction by cationic antimicrobial peptides and involvement in intrinsic polymyxin and antimicrobial peptide resistance, biofilm formation, and swarming motility of PsrA in Pseudomonas aeruginosa
    W James Gooderham
    Center for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, 232 2259 Lower Mall Research Station, Vancouver, BC, Canada
    J Bacteriol 190:5624-34. 2008
    ..This suggests that PsrA might be a key regulator of antimicrobial peptide resistance and virulence...
  37. pmc Structure and mechanism of ArnA: conformational change implies ordered dehydrogenase mechanism in key enzyme for polymyxin resistance
    Petia Z Gatzeva-Topalova
    Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, Colorado 80309, USA
    Structure 13:929-42. 2005
    ..The proposed mechanism for ArnA_DH has important implications for the design of selective inhibitors...
  38. ncbi Phosphoethanolamine substitution in the lipid A of Escherichia coli O157 : H7 and its association with PmrC
    Sang Hyun Kim
    Department of Pathobiology, Ontario Veterinary College, University of Guelph, Guelph, Ontario, Canada N1G 2W1
    Microbiology 152:657-66. 2006
    ....
  39. ncbi [Cholera in Rio Grande do Norte State--Brazil: sorology and sensitivity of Vibrio cholerae to different antimicrobials]
    Ligia Maria Rodrigues de Melo
    Universidade Potiguar, UNP, Natal, RN
    Acta Cir Bras 20:8-11. 2005
    ....
  40. ncbi Actinobacillus actinomycetemcomitans lipopolysaccharide stimulates the phosphorylation of p44 and p42 MAP kinases through CD14 and TLR-4 receptor activation in human gingival fibroblasts
    Gloria Gutiérrez-Venegas
    Laboratorio de Bioquímica División de Estudios de Posgrado Facultad de Odontología Universidad, Nacional Autónoma de México México, D F 04510
    Life Sci 78:2577-83. 2006
    ..Our data also suggest that CD14 and TLR-4 receptors are involved in the LPS effects in human gingival fibroblasts...
  41. ncbi Resistance to the antimicrobial peptide polymyxin requires myristoylation of Escherichia coli and Salmonella typhimurium lipid A
    An X Tran
    Department of Microbiology, J H Quillen College of Medicine, Johnson City, Tennessee 37614, USA
    J Biol Chem 280:28186-94. 2005
    ..In summary, we demonstrate that attachment of l-Ara4N to the phosphate groups of lipid A and the subsequent resistance to polymyxin is dependent upon the presence of the secondary linked myristoyl group...
  42. ncbi Genome-wide transcriptional response of Yersinia pestis to stressful conditions simulating phagolysosomal environments
    Dongsheng Zhou
    Laboratory of Analytical Microbiology, State Key Laboratory of Pathogen and Biosecurity, National Center for Biomedical Analysis, Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Fengtai, Beijing 100071, China
    Microbes Infect 8:2669-78. 2006
    ..This microarray analysis would provide the candidates for identifying genes or pathways required for growth and proliferation of Y. pestis in macrophages...
  43. pmc Isolation and identification of a Paenibacillus polymyxa strain that coproduces a novel lantibiotic and polymyxin
    Zengguo He
    Parker Food Science Building, The Ohio State University, 2015 Fyffe Road, Columbus, OH 43210, USA
    Appl Environ Microbiol 73:168-78. 2007
    ..The coproduction of polymyxin E1 and a lantibiotic is a finding that has not been reported earlier. The new strain and associated peptide are potentially useful in food and medical applications...
  44. ncbi Multidrug-resistant Gram-negative bacterial infections: the emerging threat and potential novel treatment options
    Paschalis I Vergidis
    Alfa Institute of Biomedical Sciences, 9 Neapoleos Street, 151 23 Marousi, Athens, Greece
    Curr Opin Investig Drugs 9:176-83. 2008
    ..b>Polymyxins are old antibiotics traditionally considered to be toxic, but which are being used because of their activity ..
  45. ncbi A single topical agent is clinically equivalent to the combination of topical and oral antibiotic treatment for otitis externa
    Peter S Roland
    Department of Otolaryngology Head Neck Surgery, University of Texas, Southwestern Medical School, Dallas TX 75235 9035, USA
    Am J Otolaryngol 29:255-61. 2008
    ....
  46. ncbi The current state of multidrug-resistant gram-negative bacilli in North America
    Anthony M Nicasio
    Center for Anti Infective Research and Development, Hartford Hospital, Hartford, CT, USA
    Pharmacotherapy 28:235-49. 2008
    ..Although still rare, Klebsiella sp that produce KPC-2 retain susceptibility only to tigecycline, polymyxins, and occasionally aminoglycosides...
  47. pmc Synthesis of and evaluation of lipid A modification by 4-substituted 4-deoxy arabinose analogs as potential inhibitors of bacterial polymyxin resistance
    T Kline
    Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA
    Bioorg Med Chem Lett 18:1507-10. 2008
    ..One compound diminished the transfer of l-Ara4N onto lipid A. These results suggest that small molecules might be designed that would effect the same reversal of bacterial resistance observed in genetic knockouts...
  48. ncbi Optimizing therapy for Acinetobacter baumannii
    Anton Y Peleg
    Division of Infectious Diseases, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA
    Semin Respir Crit Care Med 28:662-71. 2007
    ..The utility of existing and older antimicrobials such as sulbactam and the polymyxins are explored, as well as, the potential role of newer agents such as tigecycline...
  49. pmc An undecaprenyl phosphate-aminoarabinose flippase required for polymyxin resistance in Escherichia coli
    Aixin Yan
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 282:36077-89. 2007
    ..PmrM and PmrL, now renamed ArnE and ArnF because of their involvement in L-Ara4N modification of lipid A, may be subunits of an undecaprenyl phosphate-alpha-L-Ara4N flippase...
  50. doi The challenge of multidrug resistance: the treatment of gram-negative rod infections
    Anna S Levin
    Shock 30:30-3. 2008
    ..For imipenem-resistant Acinetobacter spp., most studied options are polymyxins and sulbactam...
  51. ncbi Old antibiotics for infections in critically ill patients
    Matthew E Falagas
    Alfa Institute of Biomedical Sciences AIBS, Athens, Greece
    Curr Opin Crit Care 13:592-7. 2007
    ..This review highlights the effectiveness and safety of older antibiotics when used in the treatment of infections of critically ill patients...
  52. ncbi First structure of the polymyxin resistance proteins
    Wenyu Fu
    Beijing Nuclear Magnetic Resonance Center, Peking University, No 5, Yi He Yuan, Beijing 100871, China
    Biochem Biophys Res Commun 361:1033-7. 2007
    ..Our study provides the structural basis of the novel interacting mechanism of bacterial two-component signal-transduction systems...
  53. pmc pmrA(Con) confers pmrHFIJKL-dependent EGTA and polymyxin resistance on msbB Salmonella by decorating lipid A with phosphoethanolamine
    Sean R Murray
    Department of Biology, Yale University, New Haven, Connecticut, USA
    J Bacteriol 189:5161-9. 2007
    ....
  54. ncbi Polymyxin antibiotics for gram-negative infections
    Tamra M Arnold
    Richard L Roudebush Veterans Affairs Medical Center VAMC, Indianapolis, IN 46202, and School of Medicine, University of Maryland, Baltimore, USA
    Am J Health Syst Pharm 64:819-26. 2007
    ..The role of polymyxin antibiotics in the treatment of multidrug-resistant gram-negative infections is reviewed...
  55. ncbi Pandrug-resistant Gram-negative bacteria: the dawn of the post-antibiotic era?
    Matthew E Falagas
    Alfa Institute of Biomedical Sciences AIBS, 9 Neapoleos Street, 151 23 Marousi, Athens, Greece
    Int J Antimicrob Agents 29:630-6. 2007
    ..baumannii or K. pneumoniae clinical isolates. Eleven laboratory studies reported on isolates with resistance to polymyxins, three of which (including two surveillance studies) also included data regarding PDR isolates...
  56. ncbi Interspecies signalling via the Stenotrophomonas maltophilia diffusible signal factor influences biofilm formation and polymyxin tolerance in Pseudomonas aeruginosa
    Robert P Ryan
    BIOMERIT Research Centre, Department of Microbiology, Biosciences Institute, National University of Ireland, Cork, Ireland
    Mol Microbiol 68:75-86. 2008
    ..This effect was associated with increased tolerance to polymyxins. Homologues of PA1396 occur in a number of phytopathogenic and plant-associated pseudomonads, suggesting that ..
  57. ncbi Local administration of polymyxins into the respiratory tract for the prevention and treatment of pulmonary infections in patients without cystic fibrosis
    M E Falagas
    Alfa Institute of Biomedical Sciences, Marousi, Greece
    Infection 35:3-10. 2007
    ..Among them, local administration of polymyxins into the respiratory tract represents a promising strategy...
  58. pmc MsbA transporter-dependent lipid A 1-dephosphorylation on the periplasmic surface of the inner membrane: topography of francisella novicida LpxE expressed in Escherichia coli
    Xiaoyuan Wang
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 279:49470-8. 2004
    ..Our findings provide the first direct evidence that lipid A 1-dephosphorylation catalyzed by LpxE occurs on the periplasmic surface of the inner membrane...
  59. ncbi Comparison of topical tobramycin-dexamethasone with dexamethasone-neomycin-polymyxin and neomycin-polymyxin-gramicidin for control of inflammation after cataract surgery: results of a multicenter, prospective, three-arm, randomized, double-masked, control
    Ricardo Notivol
    Clinical Research Department, Alcon Cusí, SA, Barcelona, Spain
    Clin Ther 26:1274-85. 2004
    ..Intraocular inflammation is typically treated with a combination of anti-inflammatory and anti-infective drugs. Tobramycin-dexamethasone (TD) has not been associated with any serious adverse events, indicating good tolerability...
  60. ncbi Regulation of Salmonella typhimurium virulence gene expression by cationic antimicrobial peptides
    Martin W Bader
    Departments of Microbiology and Laboratory Medicine, University of Washington Medical School, Seattle, WA 98195, USA
    Mol Microbiol 50:219-30. 2003
    ..Because bacterial resistance to oxidative stress and CAMP are induced during infection of animals, CAMP may be an important signal recognized by bacteria on colonization of animal tissues...
  61. ncbi Hyphenation of liquid chromatography to ion trap mass spectrometry to identify minor components in polypeptide antibiotics
    C Govaerts
    Laboratorium voor Farmaceutische Chemie en Analyse van Geneesmiddelen, Faculteit Farmaceutische Wetenschappen, Katholieke Universiteit Leuven, E Van Evenstraat 4, 3000, Leuven, Belgium
    Anal Bioanal Chem 377:909-21. 2003
    ..in combination with ion trap mass spectrometry was successfully applied for the characterization of impurities in gramicidin, polymyxin B, polymyxin E, and bacitracin and the study of the degradation products of polymyxins B and E.
  62. ncbi Inhibiting mild steel corrosion from sulfate-reducing bacteria using antimicrobial-producing biofilms in Three-Mile-Island process water
    R Zuo
    Departments of Chemical Engineering and Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269 3222, USA
    Appl Microbiol Biotechnol 64:275-83. 2004
    ..A consortium of beneficial bacteria (GGPST consortium, producing gramicidin S and other antimicrobials) also protected the mild steel...
  63. ncbi Isolation, structural characterization, and properties of mattacin (polymyxin M), a cyclic peptide antibiotic produced by Paenibacillus kobensis M
    Nathaniel I Martin
    Department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2, Canada
    J Biol Chem 278:13124-32. 2003
    ..The biosynthesis of mattacin was also examined briefly using transpositional mutagenesis by which 10 production mutants were obtained, revealing a set of genes involved in production...
  64. ncbi [Anti-Pseudomonas aerosol therapy in cystic fibrosis: improvement with tobramycin]
    P Foucaud
    Service de Pediatrie, Hopital Andre Mignot, Centre Hospitalier de Versailles, 78157 Le Chesnay
    Rev Pneumol Clin 58:131-8. 2002
    ..These studies have demonstrated a significant improvement of respiratory function...
  65. ncbi Cloning and characterization of the Burkholderia vietnamiensis norM gene encoding a multi-drug efflux protein
    Christine C Fehlner-Gardiner
    Department of Microbiology and Immunology, University of Western Ontario, London, Canada N6A 5C1
    FEMS Microbiol Lett 215:279-83. 2002
    ..We demonstrate that increased polymyxin sensitivity in B. vietnamiensis was associated with the presence of tetracycline in the growth medium, a phenotype that was partially suppressed by expression of the norM gene...
  66. ncbi Study of the stability of polymyxins B(1), E(1) and E(2) in aqueous solution using liquid chromatography and mass spectrometry
    J A Orwa
    Katholieke Universiteit Leuven, Faculteit Farmaceutische Wetenschappen, Laboratorium voor Farmaceutische Chemie en Analyse van Geneesmiddelen, Van Evenstraat 4, B 3000 Leuven, Belgium
    J Pharm Biomed Anal 29:203-12. 2002
    b>Polymyxins B(1), E(1) (colistin A) and E(2) (colistin B) were subjected to degradation in aqueous solutions of different pH values (1.4, 3.4, 5.4 and 7...
  67. ncbi Pitfalls of polymyxin antimicrobial susceptibility testing of Pseudomonas aeruginosa isolated from cystic fibrosis patients
    Michael Hogardt
    Max von Pettenkofer Institut fur Hygiene und Medizinische Mikrobiologie, National Consulting Laboratory Southern Germany on Cystic Fibrosis Bacteriology, Ludwig Maximilians University Munich, Germany
    J Antimicrob Chemother 54:1057-61. 2004
    With their potent activity against Gram-negative bacteria, the polymyxins are important alternative antibiotics for cystic fibrosis (CF) patients...
  68. ncbi The pmrF polymyxin-resistance operon of Yersinia pseudotuberculosis is upregulated by the PhoP-PhoQ two-component system but not by PmrA-PmrB, and is not required for virulence
    M Marceau
    E0364 Inserm Université Lille II Faculté de Médecine Henri Warembourg Institut Pasteur de Lille, Lille, France
    Microbiology 150:3947-57. 2004
    ..typhimurium. The marked differences in pmrF operon regulation in these two phylogenetically close bacterial species may be related to their dissimilar lifestyles...
  69. ncbi [Sensitivity to colistin: evaluation of cut-off points available in disk diffusion test]
    C H Rodriguez
    Laboratorio de Bacteriologia, Departamento de Bioquimica Clinica, Hospital de Clinicas Jose de San Martin, Argentina
    Rev Argent Microbiol 36:125-9. 2004
    ....
  70. ncbi IMPs, VIMs and SPMs: the diversity of metallo-beta-lactamases produced by carbapenem-resistant Pseudomonas aeruginosa in a Brazilian hospital
    H S Sader
    Laboratorio Alerta e Laboratorio Especial de Microbiologia Clínica, Disciplina de Doencas Infecciosas e Parasitarias, Universidade Federal de Sao Paulo, Sao Paulo, Brazil
    Clin Microbiol Infect 11:73-6. 2005
    ..The polymyxins were the most active compounds (100% susceptibility), followed by amikacin and cefepime (59.0%), meropenem (57...
  71. ncbi [Antimicrobial mechanisms of action]
    Jorge Calvo
    Servicio de Microbiologia, Hospital Universitario Marques de Valdecilla, Santander, Espana
    Enferm Infecc Microbiol Clin 27:44-52. 2009
    ..The main drugs affecting the cytoplasmic membrane are polymyxins and daptomycin...
  72. pmc In-vitro activity of polymyxin B in combination with imipenem, rifampicin and azithromycin versus multidrug resistant strains of Acinetobacter baumannii producing OXA-23 carbapenemases
    David W Wareham
    Centre for Infectious Disease, Institute of Cell and Molecular Science, Barts and The London, Queen Mary s School of Medicine and Dentistry, London, UK
    Ann Clin Microbiol Antimicrob 5:10. 2006
    ..Many of the circulating strains exhibit multi-drug resistance remaining consistently susceptible only to polymyxins. In-vitro studies have reported that polymyxins combined with carbapenems, rifampicin or azithromycin are ..
  73. ncbi Multi-drug resistant Pseudomonas aeruginosa and Acinetobacter baumannii infections among hospitalized patients: risk factors and outcomes
    M Shanthi
    Department of Microbiology, Sri Ramachandra Medical College and Research Institute, Chennai 600116
    J Assoc Physicians India 57:636, 638-40, 645. 2009
    ..This study was undertaken to determine the prevalence of MBL production in carbapenem-resistant isolates and to study the factors influencing the clinical outcomes of infections...
  74. pmc Efflux-mediated aminoglycoside and macrolide resistance in Burkholderia pseudomallei
    R A Moore
    Department of Microbiology and Infectious Diseases, University of Calgary Health Sciences Centre, Alberta, Canada
    Antimicrob Agents Chemother 43:465-70. 1999
    ..resistant to a wide range of antimicrobial agents including beta-lactams, aminoglycosides, macrolides, and polymyxins. We used Tn5-OT182 to mutagenize B. pseudomallei to identify the genes involved in aminoglycoside resistance...
  75. ncbi Treatment of Acinetobacter infections
    Argyris Michalopoulos
    ICU, Henry Dunant Hospital, Athens, Greece
    Expert Opin Pharmacother 11:779-88. 2010
    ..It commonly presents resistance to multiple antimicrobial agents, occasionally including carbapenems and polymyxins, and hence, it is considered the paradigm of multidrug-resistant (MDR) or pandrug-resistant (PDR) bacterium...
  76. ncbi Colistin therapy for microbiologically documented multidrug-resistant Gram-negative bacterial infections: a retrospective cohort study of 258 patients
    Matthew E Falagas
    Alfa Institute of Biomedical Sciences AIBS, 9 Neapoleos Street, 15 123 Marousi, Athens, Greece
    Int J Antimicrob Agents 35:194-9. 2010
    It is unclear whether the effectiveness of polymyxins depends on the site of infection, the responsible pathogen, dosage, and monotherapy vs. combination therapy...
  77. ncbi Extended-spectrum beta-lactamase-producing organisms
    M E Falagas
    Alfa Institute of Biomedical Sciences, 9 Neapoleos Street, 151 23 Marousi, Athens, Greece
    J Hosp Infect 73:345-54. 2009
    ..Tigecycline and polymyxins have substantial antimicrobial activity against ESBL-producing Enterobacteriaceae, and, along with fosfomycin, ..
  78. ncbi Management of complicated urinary tract infections in the era of antimicrobial resistance
    Mazen S Bader
    McMaster University, Faculty of Health Sciences, Division of Infectious Diseases, Hamilton, Ontario, Canada
    Postgrad Med 122:7-15. 2010
    ..Aminoglycosides, tigecycline, and polymyxins can be used for the treatment of serious cUTIs when first-line options are deemed to be inappropriate or ..
  79. pmc Synergy between polyethylenimine and different families of antibiotics against a resistant clinical isolate of Pseudomonas aeruginosa
    Hayssam Khalil
    Faculty of Life Sciences, Northwestern Polytechnical University, Xi an, Shaanxi 710072, People s Republic of China
    Antimicrob Agents Chemother 52:1635-41. 2008
    ..5- to 56-fold. However, the MICs of aminoglycosides, polymyxins, and vancomycins were increased by 1...
  80. ncbi Investigation of colistin sensitivity via three different methods in Acinetobacter baumannii isolates with multiple antibiotic resistance
    Melda Sinirtas
    Department of Microbiology and Infectious Diseases, Uludag University School of Medicine, Bursa, Turkey
    Int J Infect Dis 13:e217-20. 2009
    ..infections caused by Acinetobacter baumannii with multiple antibiotic resistance, which has lead to the use of polymyxins, especially colistin, being reconsidered. The aim of this study was to investigate the colistin sensitivity of A...
  81. ncbi Pseudomonas aeruginosa susceptible only to colistin in intensive care unit patients
    Aikaterini Mastoraki
    Surgical Intensive Care Unit, Onassis Cardiac Surgery Center, Athens, Greece
    Surg Infect (Larchmt) 9:153-60. 2008
    ..The aim of this study was to determine the incidence of MDR strains of Pseudomonas in patients undergoing cardiac surgery, to elucidate the effectiveness of treating these patients with colistin, and to assess the safety of the drug...
  82. ncbi Intravenous colistin sulfate: a rarely used form of polymyxin E for the treatment of severe multidrug-resistant Gram-negative bacterial infections
    Jie Huang
    Shanghai Jiaotong University, Shanghai, China
    Scand J Infect Dis 42:260-5. 2010
    In recent reports polymyxins have been considered an effective and safe treatment option for the management of multidrug-resistant (MDR) Gram-negative bacterial infections...
  83. ncbi Resistance in nonfermenting gram-negative bacteria: multidrug resistance to the maximum
    John E McGowan
    Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA
    Am J Infect Control 34:S29-37; discussion S64-73. 2006
    ..b>Polymyxins are the remaining antibiotic drug class with fairly consistent activity against multidrug-resistant strains of P ..
  84. pmc Temperature dependence of the binding of endotoxins to the polycationic peptides polymyxin B and its nonapeptide
    Klaus Brandenburg
    Forschungszentrum Borstel, Leibniz Zentrum für Medizin und Biowissenschaften, D 23845 Borstel, Germany
    Biophys J 88:1845-58. 2005
    ..lipid A) an exothermic reaction takes place, which is mainly due to the strong electrostatic interaction of the polymyxins with the negative charges of the endotoxins, i.e...
  85. ncbi Resistance in nonfermenting gram-negative bacteria: multidrug resistance to the maximum
    John E McGowan
    Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia 30322, USA
    Am J Med 119:S29-36; discussion S62-70. 2006
    ..b>Polymyxins are the remaining antibiotic drug class with fairly consistent activity against multidrug-resistant strains of P ..
  86. pmc BpeAB-OprB, a multidrug efflux pump in Burkholderia pseudomallei
    Y Y Chan
    Department of Biochemistry, Faculty of Medicine, National University of Singapore, Singapore 117597, Singapore
    Antimicrob Agents Chemother 48:1128-35. 2004
    ..resistant to a wide range of antimicrobial agents, including beta-lactams, aminoglycosides, macrolides, and polymyxins. An operon, bpeR-bpeA-bpeB-oprB, which encodes a putative repressor, a membrane fusion protein, an inner ..
  87. pmc Administration of antibiotics via the respiratory tract for the prevention of ICU-acquired pneumonia: a meta-analysis of comparative trials
    Matthew E Falagas
    Alfa Institute of Biomedical Sciences AIBS, Athens, Greece
    Crit Care 10:R123. 2006
    ....
  88. pmc Involvement of pmrAB and phoPQ in polymyxin B adaptation and inducible resistance in non-cystic fibrosis clinical isolates of Pseudomonas aeruginosa
    Kristen N Schurek
    Centre for Microbial Diseases and Immunity Research, University of British Columbia, 2259 Lower Mall, Vancouver, British Columbia, Canada
    Antimicrob Agents Chemother 53:4345-51. 2009
    During investigation of susceptibility testing methods for polymyxins, 24 multidrug-resistant clinical isolates of Pseudomonas aeruginosa were observed to have a distinct, reproducible phenotype in which skipped wells were observed during ..
  89. ncbi Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections
    Matthew E Falagas
    Alfa Institute of Biomedical Sciences, Athens, Greece
    Clin Infect Dis 40:1333-41. 2005
    ..gram-negative bacteria and the lack of new antibiotics to combat them have led to the revival of polymyxins, an old class of cationic, cyclic polypeptide antibiotics...
  90. pmc Adaptive resistance to the "last hope" antibiotics polymyxin B and colistin in Pseudomonas aeruginosa is mediated by the novel two-component regulatory system ParR-ParS
    Lucía Fernández
    Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, 232 2259 Lower Mall Research Station, Vancouver, BC, Canada V6T 1Z4
    Antimicrob Agents Chemother 54:3372-82. 2010
    ..In this opportunistic pathogen, subinhibitory levels of polymyxins and certain antimicrobial peptides induce resistance toward higher, otherwise lethal, levels of these ..
  91. ncbi LC-MS/MS method development and validation for the determination of polymyxins and vancomycin in rat plasma
    Chang Cheng
    Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK 73019, USA
    J Chromatogr B Analyt Technol Biomed Life Sci 878:2831-8. 2010
    ..mass spectrometer (LC-MS/MS) methods were developed and validated for the determination of lipopeptide polymyxins and glycopeptide vancomycin in rat plasma...
  92. ncbi Multidrug-resistant Gram-negative bacteria: how to treat and for how long
    Helen Giamarellou
    Athens University Medical School, Athens, Greece
    Int J Antimicrob Agents 36:S50-4. 2010
    ..b>Polymyxins, known since 1947, are mostly represented by polymyxin E (colistin), which has recently gained a principal ..
  93. ncbi [The antibiotic susceptibility of Campylobacter strains isolated in Moldova. The possibilities for estimation and the results]
    L Sicinschi
    ,
    Bacteriol Virusol Parazitol Epidemiol 41:123-9. 1996
    ..The MICs (90%) of ampicillin, cephotaxime, erythromycin, colistin and metronidazole exceeded slightly the respective standard data. The MICs for the rest of the antibiotics were lower than the accepted international concentrations...
  94. ncbi Polymyxin B: similarities to and differences from colistin (polymyxin E)
    Andrea Kwa
    Singapore General Hospital, Outram Road, 169608, Singapore
    Expert Rev Anti Infect Ther 5:811-21. 2007
    ..b>Polymyxins, a group of antibacterials that were discovered during the late 1940s, represent some of the last treatment ..
  95. pmc A novel polymyxin derivative that lacks the fatty acid tail and carries only three positive charges has strong synergism with agents excluded by the intact outer membrane
    Martti Vaara
    Northern Antibiotics Ltd, Eskolantie 1, FI 00720 Helsinki, Finland
    Antimicrob Agents Chemother 54:3341-6. 2010
    b>Polymyxins are cationic lipopeptides (five cationic charges) and the last resort for the treatment of serious Gram-negative infections caused by multiresistant strains...
  96. ncbi Optimizing use of colistin and polymyxin B in the critically ill
    Roger L Nation
    Facility for Anti Infective Drug Development and Innovation, Victorian College of Pharmacy, Monash University, 381 Royal Parade, Parkville, Victoria, Australia
    Semin Respir Crit Care Med 28:604-14. 2007
    ..Although the polymyxins have been available in the clinic for around 50 years, they have never been subjected to the drug development ..
  97. ncbi Current control and treatment of multidrug-resistant Acinetobacter baumannii infections
    Drosos E Karageorgopoulos
    Alfa Institute of Biomedical Sciences, Athens, Greece
    Lancet Infect Dis 8:751-62. 2008
    ..b>Polymyxins show reliable antimicrobial activity against A baumannii isolates...
  98. ncbi Effect of polymyxin B and environmental conditions on isolation of Brucella species and the vaccine strain RB51
    Allen E Jensen
    National Animal Disease Center, United States Department of Agriculture, Ames, IA 50010, USA
    Comp Immunol Microbiol Infect Dis 33:121-31. 2010
    ..Both B. melitensis and B. suis were the least susceptible to polymyxins and rough strains were more susceptible to both PB and COL than the smooth except for the BvrR mutant...
  99. ncbi Synthesis and characterization of the colistin peptide polymyxin E1 and related antimicrobial peptides
    T Kline
    PathoGenesis Corporation, Seattle, Washington 98119, USA
    J Pept Res 57:175-87. 2001
    Two strategies were developed to synthesize the acylated cyclic peptides know as polymyxins. Synthesis of polymyxin E1 and several analogs enabled us to evaluate the minimum inhibitory concentration of individual compounds against Gram-..
  100. ncbi Detection and treatment options for Klebsiella pneumoniae carbapenemases (KPCs): an emerging cause of multidrug-resistant infection
    Elizabeth B Hirsch
    University of Houston College of Pharmacy, and St Luke s Episcopal Hospital, Houston, TX, USA
    J Antimicrob Chemother 65:1119-25. 2010
    ..Clinical success rates were low when the polymyxins were used as monotherapy, but were much higher when they were used in combination...
  101. pmc Toxicity after prolonged (more than four weeks) administration of intravenous colistin
    Matthew E Falagas
    Alfa Institute of Biomedical Sciences, Athens, Greece
    BMC Infect Dis 5:1. 2005
    The intravenous use of polymyxins has been considered to be associated with considerable nephrotoxicity and neurotoxicity...

Research Grants15

  1. Targeting superbugs: discovery and development of new broad-spectrum lipopeptides
    Jian Li; Fiscal Year: 2013
    ..aeruginosa, A. baumannii and K. pneumoniae will be available for many years to come. Polymyxins (i.e...
  2. Inhibitors of isoprenoid synthesis for antibacterial therapy
    Donald T Moir; Fiscal Year: 2013
    ..Multidrug resistance is increasing among Gr(-) nonfermenters, and as a last resort, polymyxins such as colistin have been revived for use against these infections...
  3. ArmR: a novel drug target and mediator of antibiotic resistance
    David S Weiss; Fiscal Year: 2013
    ..Modification of lipid A surface chaRge) that is widely conserved and which we show is required for resistance to polymyxins in A. baumannii as well as other Gram-negative bacteria...
  4. Genetic determinants of antimicrobial peptide resistance in Gram negative bacteri
    Hyunwoo Lee; Fiscal Year: 2010
    ..Only a few such peptides, e.g., polymyxins, have been in clinical practice, and to date polymyxins are the only antibiotic to which multidrug-resistant ..
  5. Polymyxin-resistant Pseudomonas in CF Lung Infection
    Samuel M Moskowitz; Fiscal Year: 2010
    ..An interdisciplinary study of polymyxin resistant Pseudomonas from patients with cystic fibrosis is proposed to pinpoint the bacterial genes responsible for this resistance, so that management strategies may be devised to overcome it. ..
  6. DEVELOPMENT OF NEW LIPID A BINDING AGENTS
    Paul Savage; Fiscal Year: 2002
    ..Association of PMB and the new LA-binders with LA and LA derivatives will be compared using microtitration calorimetry. ..
  7. Hydrophobic Polyamine Amides as Anti-Endotoxin Agents
    Sunil David; Fiscal Year: 2007
    ..The toxicity of the compounds will be systematically determined in a panel of in vitro assays. These studies will serve to generate data for anticipated IND submissions. [unreadable] [unreadable]..
  8. Rational Development of Endotoxin Sequestering Agents
    Sunil David; Fiscal Year: 2006
    ..Highly active molecules will be further tested in two murine models of gram-negative sepsis. The toxicity of the compounds will be systematically determined in a panel of in vitro assays. ..
  9. Optimizing dosing to prevent antibiotic resistance
    Martin Evans; Fiscal Year: 2005
    ..We believe understanding the mechanisms underlying resistance will enhance our ability to design alternative dosing strategies to effect clinical cure. ..
  10. Gram-Negative Sepsis: Pharmacophore-Based Therapeutics
    Sunil David; Fiscal Year: 2007
    ..abstract_text> ..
  11. Development and evaluation of subunit vaccine CmeC against Campylobacter jejuni
    Jun Lin; Fiscal Year: 2008
    ..S. The proposed research will provide novel information on the development of effective vaccine against C. jejuni to protect public health. [unreadable] [unreadable] [unreadable]..
  12. Role of Surfactant in Innate and Adaptive Immunity
    Jo Rae Wright; Fiscal Year: 2010
    ..abstract_text> ..
  13. Novel High-throghput Assay:Angiogenesis Inhibitors (RMI)
    Sunil David; Fiscal Year: 2004
    ..Promising compounds will be examined in greater detail with respect to details of the physical interactions with heparin. Further biological activity will be ascertained in chicken chorioallantoic membrane assays. ..
  14. Novel Leads for the Therapy of Gram-Positive Sepsis
    Sunil David; Fiscal Year: 2004
    ..This is to demonstrate that inhibition of cytokine release, if observed, is attributable to the blockade of the cellular recognition of lipoteichoic acid. ..
  15. ROLE OF SURFACTANT PROTEINS IN PULMONARY HOST DEFENSE
    Jo Rae Wright; Fiscal Year: 2008
    ....