Research Topics
Genomes and Genes | AMBROSE LIN YAU CHEUNGSummaryAffiliation: Dartmouth Medical School Country: USA Publications
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Publications
Global regulation of virulence determinants in Staphylococcus aureus by the SarA protein familyAmbrose L Cheung
Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, NH 03755, USA
Front Biosci 7:d1825-42. 2002..g. alpha-hemolysin) will be important to our eventual goal of disrupting the regulatory network...- The SarA protein family of Staphylococcus aureusAmbrose L Cheung
Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, NH 03755, USA
Int J Biochem Cell Biol 40:355-61. 2008..Mutagenesis studies of SarA disclose that the winged helix motifs are important for DNA binding and function. Recent progress concerning the functions and plausible mechanisms of regulation of SarA and its homologs are discussed... - SarA of Staphylococcus aureus binds to the sarA promoter to regulate gene expressionAmbrose L Cheung
Department of Microbiology and Immunology, Vail 210, Dartmouth Medical School, Hanover, NH 03766, USA
J Bacteriol 190:2239-43. 2008..Together with the results of transcription analyses, our data indicate that SarA binds to its own promoter to down-regulate sarA expression... - Regulation of the mazEF toxin-antitoxin module in Staphylococcus aureus and its impact on sigB expressionNiles P Donegan
Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, NH 03755, USA
J Bacteriol 191:2795-805. 2009..The antibiotic response also appears to occur in two other TA systems in S. aureus, indicating a shared mechanism of regulation... - Role of ArlRS in autolysis in methicillin-sensitive and methicillin-resistant Staphylococcus aureus strainsGuido Memmi
Department of Microbiology, Dartmouth Medical School, Hanover, New Hampshire, USA
J Bacteriol 194:759-67. 2012..Also, the autolytic phenotype in the arlRS mutant of MSSA strain Newman could be rescued by a mutation in either atl or lytM. Together, these data showed that ArlRS impacts autolysis differently in MSSA and MRSA strains... - Regulation of virulence determinants in vitro and in vivo in Staphylococcus aureusAmbrose L Cheung
Department of Microbiology, Dartmouth Medical School, Hanover, NH 03755, USA
FEMS Immunol Med Microbiol 40:1-9. 2004..Recent data using reporter gene fusions in animal models, have confirmed distinct expression profiles of selected regulatory and target genes in vitro vs. in vivo... - Rat/MgrA, a regulator of autolysis, is a regulator of virulence genes in Staphylococcus aureusSusham Ingavale
Department of Microbiology, Dartmouth Medical School, Hanover, NH 03755, USA
Infect Immun 73:1423-31. 2005..Thus, our studies here have defined the nature of interaction of mgrA with other regulators such as agr, sarS, and sarT and its role in regulating hla and spa transcription within the virulence regulatory network of S. aureus... - The staphylococcus-specific gene rsr represses agr and virulence in Staphylococcus aureusSandeep Tamber
Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, NH 03755, USA
Infect Immun 78:4384-91. 2010..We also provide evidence using a murine model of S. aureus skin infection that the effects mediated by rsr reduce disease progression... - SarZ promotes the expression of virulence factors and represses biofilm formation by modulating SarA and agr in Staphylococcus aureusSandeep Tamber
Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, NH 03755, USA
Infect Immun 77:419-28. 2009..Together, our results indicate that SarZ may be an important regulator governing the dissemination phase of S. aureus infections, as it promotes toxin expression while repressing factors required for biofilm formation... - Role of mgrA and sarA in methicillin-resistant Staphylococcus aureus autolysis and resistance to cell wall-active antibioticsMaria Pilar Trotonda
Department of Microbiology, Dartmouth Medical School, Hanover, New Hampshire, USA
J Infect Dis 199:209-18. 2009..We have previously shown the importance of mgrA and sarA in controlling autolysis of Staphylococcus aureus, with MgrA and SarA both being negative regulators of murein hydrolases... - Interconnections between Sigma B, agr, and proteolytic activity in Staphylococcus aureus biofilm maturationKatherine J Lauderdale
Department of Microbiology, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Infect Immun 77:1623-35. 2009..Altogether, our observations demonstrate that SigB is an essential regulator of S. aureus biofilm maturation... - MgrA represses biofilm formation in Staphylococcus aureusMaria Pilar Trotonda
Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, NH 03755, USA
Infect Immun 76:5645-54. 2008..Collectively, our data showed MgrA to be a repressor of biofilm formation, and biofilms formed by mgrA mutants have features that are distinct from other reported biofilm types in S. aureus... - The expression of alpha-haemolysin is required for Staphylococcus aureus phagosomal escape after internalization in CFT-1 cellsTodd M Jarry
Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, NH 03755, USA
Cell Microbiol 10:1801-14. 2008..These results demonstrate that the expression of agr is required for vesicular escape, and that biologically active alpha-haemolysin is required for S. aureus escape from the endocytic vesicle into the cytosol of CFT-1 cells... - Role of PknB kinase in antibiotic resistance and virulence in community-acquired methicillin-resistant Staphylococcus aureus strain USA300Sandeep Tamber
Department of Microbiology, Dartmouth Medical School, Hanover, NH 03755, USA
Infect Immun 78:3637-46. 2010.... - Regulation of Staphylococcus aureus type 5 capsular polysaccharides by agr and sarA in vitro and in an experimental endocarditis modelWillem van Wamel
Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, NH 03755, USA
Microb Pathog 33:73-9. 2002..In addition, the regulation ofcap5 expression by these global regulators may vary in distinct anatomic niches in vivo... - SarT influences sarS expression in Staphylococcus aureusKatherine A Schmidt
Department of Microbiology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
Infect Immun 71:5139-48. 2003..Induction of sarS and spa by SarT in agr(+) strains was confirmed by a tetracycline-inducible system to titrate sarT expression... - sarU, a sarA homolog, is repressed by SarT and regulates virulence genes in Staphylococcus aureusAdhar C Manna
Department of Microbiology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
Infect Immun 71:343-53. 2003..g., those found in vivo) might repress sarT, leading to increased expression of sarU. Elevated sarU expression would result in additional amplification of the original agr signal... - Identification of sarV (SA2062), a new transcriptional regulator, is repressed by SarA and MgrA (SA0641) and involved in the regulation of autolysis in Staphylococcus aureusAdhar C Manna
Department of Microbiology, Dartmouth Medical School, Hanover, NH 03755, USA
J Bacteriol 186:5267-80. 2004..aureus. We propose that sarV may be part of the common pathway by which mgrA and sarA gene products control autolysis in S. aureus... - Role of the distal sarA promoters in SarA expression in Staphylococcus aureusAmbrose L Cheung
Department of Microbiology and Immunology, Dartmouth Medical School, Vail 205, Hanover, New Hampshire 03755, USA
Infect Immun 73:4391-4. 2005.... - Overexpression of MazFsa in Staphylococcus aureus induces bacteriostasis by selectively targeting mRNAs for cleavageZhibiao Fu
Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, NH 03755, USA
J Bacteriol 191:2051-9. 2009..These data suggest that S. aureus likely undergoes stasis by protecting selective mRNA with RNA-binding proteins upon the expression of MazF(Sa) in vivo... - Proteolytic regulation of toxin-antitoxin systems by ClpPC in Staphylococcus aureusNiles P Donegan
Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, NH 03755, USA
J Bacteriol 192:1416-22. 2010..From these studies, we concluded that ClpPC serves as the functional unit for the degradation of all known antitoxins in S. aureus... - Disparity in the in vitro versus in vivo regulation of fibronectin-binding proteins by 2 global regulators, saeRS and sigB, in Staphylococcus aureusAmbrose L Cheung
Department of Microbiology, Dartmouth Medical School, Hanover, New Hampshire, USA
J Infect Dis 200:1371-4. 2009..Moreover, as opposed to the in vitro findings, sigB appeared to have a positive rather than a negative effect on saeRS expression within cardiac vegetations... - Characterization of MazFSa, an endoribonuclease from Staphylococcus aureusZhibiao Fu
Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, NH 03755, USA
J Bacteriol 189:8871-9. 2007..These data indicate that the mazEF system of S. aureus differs from the gram-negative counterparts with respect to mRNA cleavage specificity and antibiotic stresses... - Heparin stimulates Staphylococcus aureus biofilm formationRobert M Q Shanks
Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA
Infect Immun 73:4596-606. 2005..These finding suggests that heparin stimulates S. aureus biofilm formation via a novel pathway... - Genetic evidence for an alternative citrate-dependent biofilm formation pathway in Staphylococcus aureus that is dependent on fibronectin binding proteins and the GraRS two-component regulatory systemRobert M Q Shanks
Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, NH 03755, USA
Infect Immun 76:2469-77. 2008..aureus catheter models of infection, we propose that the citrate-stimulated biofilm formation pathway may represent a clinically relevant pathway for the formation of these bacterial communities on medical implants... - Coordinated regulation by AgrA, SarA, and SarR to control agr expression in Staphylococcus aureusDindo Reyes
Department of Microbiology, Dartmouth Medical School, Hanover, New Hampshire 037551, USA
J Bacteriol 193:6020-31. 2011.... - Whole-genome sequencing of Staphylococcus aureus strain RN4220, a key laboratory strain used in virulence research, identifies mutations that affect not only virulence factors but also the fitness of the strainDhanalakshmi Nair
Department of Microbiology, Dartmouth Medical School, Hanover, NH 03755, USA
J Bacteriol 193:2332-5. 2011..Using whole-genome sequencing, we showed that RN4220 differs from NCTC8325 and contains a number of genetic polymorphisms that affect both virulence and general fitness, implying a need for caution in using this strain for such studies... - Staphylococcus aureus escapes more efficiently from the phagosome of a cystic fibrosis bronchial epithelial cell line than from its normal counterpartTodd M Jarry
Department of Microbiology and Immunology, Dartmouth Medical School, Hanover, NH 03755, USA
Infect Immun 74:2568-77. 2006..These results demonstrate a fundamental difference in the fate of live S. aureus after invasion of CFT-1 versus LCFSN cell lines and may explain the propensity of S. aureus to cause chronic lung infection in CF patients... - Tissue culture assays used to analyze invasion by Staphylococcus aureusAmbrose L Cheung
Dartmouth Medical School, Hanover, New Hampshire, USA
Curr Protoc Microbiol . 2007..In this unit, we describe two cell culture models, including bovine mammary epithelial cells and human umbilical vein endothelial cells, that investigators have used to study the interactions of S. aureus with host cells... - Fibrinogen depletion attenuates Staphyloccocus aureus infection by preventing density-dependent virulence gene up-regulationJacob M Rothfork
Research Service, Albuquerque Veterans Affairs Medical Center, Albuquerque, NM 87108, USA
J Immunol 171:5389-95. 2003..These data demonstrate that down-modulation of specific inflammatory components of the host that augment bacterial quorum sensing can be a strategy for enhancing host defense against infection... - SarA positively controls bap-dependent biofilm formation in Staphylococcus aureusMaria Pilar Trotonda
Instituto Valenciano de Investigaciones Agrarias, Carretera Náquera Moncada Km 4, 5, 46113 Moncada, Valencia, Spain
J Bacteriol 187:5790-8. 2005..Based on the previous studies of others as well as our work demonstrating the role for SarA in icaADBC and bap expression, we propose that SarA is an essential regulator controlling biofilm formation in S. aureus... - Salicylic acid attenuates virulence in endovascular infections by targeting global regulatory pathways in Staphylococcus aureusLeon Iri Kupferwasser
Division of Infectious Disease, Harbor-UCLA (University of California-Los Angeles, Torrance, California, USA
J Clin Invest 112:222-33. 2003..aureus, by downmodulating key staphylococcal global regulons and structural genes in vivo, thus abrogating relevant virulence phenotypes... - Crystal structure of the SarS protein from Staphylococcus aureusRonggui Li
Integrated Department of Immunology, National Jewish Medical and Research Center, and Department of Pharmacology, Biomolecular Structure Program, School of Medicine, University of Colorado Health Science Center, Denver, Colorado 80206, USA
J Bacteriol 185:4219-25. 2003..Based on the structural differences of SarR, SarS, and MarR, we further classified these winged-helix proteins to three subfamilies, SarA, SarS, and MarR. Finally, a possible transcription regulation mechanism is proposed... - Transcriptional regulation of the agr locus and the identification of DNA binding residues of the global regulatory protein SarR in Staphylococcus aureusAdhar C Manna
Division of Basic Biomedical Sciences, University of South Dakota School of Medicine, Vermillion, SD 57069, USA
Mol Microbiol 60:1289-301. 2006..Interestingly, SarR and SarA binding sites on the agr promoter are confined within the same region of DNA. Additional gel shift studies with SarR and SarA suggest that these two proteins may bind the same region of the agr promoter... - Activation and transcriptional interaction between agr RNAII and RNAIII in Staphylococcus aureus in vitro and in an experimental endocarditis modelYan-Qiong Xiong
Division of Infectious Diseases, Harbor-University of California, Los Angeles, USA
J Infect Dis 186:668-77. 2002..These data demonstrate that RNAIII activation in vivo is time and cell density dependent, may be tissue specific, and can occur through RNAII-dependent and -independent mechanisms... - A recA-LexA-dependent pathway mediates ciprofloxacin-induced fibronectin binding in Staphylococcus aureusCarmelo Bisognano
Division of Infectious Diseases, University Hospital, CH-1211 Geneva 14, Switzerland
J Biol Chem 279:9064-71. 2004..We conclude that activation of recA and derepression of lexA-regulated genes by CPX may represent a response to drug-induced damage that results in a novel induction of a virulence factor leading to increased bacterial tissue adherence... - Impacts of sarA and agr in Staphylococcus aureus strain Newman on fibronectin-binding protein A gene expression and fibronectin adherence capacity in vitro and in experimental infective endocarditisYan-Qiong Xiong
Department of Medicine, Division of Infectious Diseases, Harbor-UCLA Research and Education Institute, Torrance, California, USA
Infect Immun 72:1832-6. 2004..Thus, additional regulatory loci contribute to fnbA regulation and fibronectin-binding capacities in S. aureus... - Thymidine-dependent Staphylococcus aureus small-colony variants are associated with extensive alterations in regulator and virulence gene expression profilesBarbara C Kahl
Institute of Medical Microbiology, University Clinics of Muenster, Domagkstr 10, 48149 Muenster, Germany
Infect Immun 73:4119-26. 2005.... - Expression of SarX, a negative regulator of agr and exoprotein synthesis, is activated by MgrA in Staphylococcus aureusAdhar C Manna
Division of Basic Biomedical Sciences, University of South Dakota Sanford School of Medicine, 414 E Clark Street, Vermillion, SD 57069, USA
J Bacteriol 188:4288-99. 2006..We propose that SarX is an important regulator in the SarA protein family and may be part of the common pathway by which agr and members of the sarA gene family control virulence in S. aureus... - Regulation of Staphylococcus aureus alpha-toxin gene (hla) expression by agr, sarA, and sae in vitro and in experimental infective endocarditisYan Q Xiong
Department of Medicine, Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor University of California Los Angeles Medical Center, Torrance, CA, USA
J Infect Dis 194:1267-75. 2006..However, their relative in vivo contributions to hla expression, particularly in endovascular infections, have not been defined... - Aspirin treatment is associated with a significantly decreased risk of Staphylococcus aureus bacteremia in hemodialysis patients with tunneled cathetersMartin Sedlacek
Division of Nephrology, Dartmouth Hitchcock Medical Center, Lebanon, NH 03756 0001, USA
Am J Kidney Dis 49:401-8. 2007..We hypothesized that long-term treatment with aspirin may decrease the frequency of S aureus bacteremia in such patients... - Minocycline modulates neuroinflammation independently of its antimicrobial activity in staphylococcus aureus-induced brain abscessTammy Kielian
Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, 4301 W Markham St, Slot 846, Little Rock, AR 72205, USA
Am J Pathol 171:1199-214. 2007.... - Structural and function analyses of the global regulatory protein SarA from Staphylococcus aureusYingfang Liu
Integrated Department of Immunology, National Jewish Medical and Research Center, Biomolecular Structure Program and Department of Pharmacology, School of Medicine, University of Colorado Health Science Center, Denver, CO 80206, USA
Proc Natl Acad Sci U S A 103:2392-7. 2006..These data suggest that the winged region of the winged helix protein participates in DNA binding and activation, whereas the putative divalent cation binding pocket is only involved in gene function... - SarA is an essential positive regulator of Staphylococcus epidermidis biofilm developmentMaria Angeles Tormo
Departamento de Quimica, Bioquimica y Biologia Molecular, Universidad Cardenal Herrera CEU, Carretera Náquera Moncada, Km 4, 5 46113 Moncada, Valencia, Spain
J Bacteriol 187:2348-56. 2005..Additionally, we present experimental evidence showing that SarA may be an important regulatory element that controls S. epidermidis virulence factors other than biofilm formation... - Inactivation of a bacterial virulence pheromone by phagocyte-derived oxidants: new role for the NADPH oxidase in host defenseJacob M Rothfork
Research Service, Albuquerque Veterans Affairs Medical Center, Albuquerque, NM 87108, USA
Proc Natl Acad Sci U S A 101:13867-72. 2004..Thus, oxidant-mediated inactivation of an autoinducing peptide from S. aureus is a critical innate defense mechanism against infection with this pathogen... - Inflammasome-mediated production of IL-1beta is required for neutrophil recruitment against Staphylococcus aureus in vivoLloyd S Miller
Division of Dermatology, University of California, Los Angeles, CA 90095, USA
J Immunol 179:6933-42. 2007..aureus in vivo... - MyD88 mediates neutrophil recruitment initiated by IL-1R but not TLR2 activation in immunity against Staphylococcus aureusLloyd S Miller
Division of Dermatology, David Geffen School of Medicine at UCLA, 52 121 CHS, 10833 Le Conte Avenue, Los Angeles, California 90095, USA
Immunity 24:79-91. 2006..This neutrophil recruitment was not dependent upon IL-1R/MyD88 signaling by recruited bone marrow-derived cells, suggesting that resident skin cells utilize IL-1R/MyD88 signaling to promote neutrophil recruitment... - Transposon disruption of the complex I NADH oxidoreductase gene (snoD) in Staphylococcus aureus is associated with reduced susceptibility to the microbicidal activity of thrombin-induced platelet microbicidal protein 1Arnold S Bayer
Department of Medical Microbiology and Immunology, University of Wisconsin, 1300 University Avenue, Biochemistry Building, Room 250, Madison, WI 53706, USA
J Bacteriol 188:211-22. 2006..aureus nuo orthologue). These novel findings indicate that disruption of a complex I enzyme locus can confer reduced in vitro susceptibility to tPMP-1 in S. aureus...
Research Grants
- Rat, a regulator of autolysis in S. aureusAmbrose Cheung; Fiscal Year: 2007..Our long-term goal is to promote autolysis with an anti-Rat or pro-SarV strategy without developing an untoward impact on virulence. ..
- The toxin-antitoxin system of Staphylococcus aureus.Ambrose Cheung; Fiscal Year: 2009..As therapy options against multidrug resistant S. aureus are limited, our screening assays will provide the initial compounds against MazE for the development of novel antimicrobial therapy against S. aureus ..
- IN VIVO GENE EXPRESSION IN STAPHYLOCCUS AUREUSAmbrose Cheung; Fiscal Year: 2009..Upon the completion of these studies, we hope to understand how sae is activated in vivo and what target genes sae impacts during infection. ..
- Characterization of sar-agr Interactions in S. aureusAMBROSE LIN YAU CHEUNG; Fiscal Year: 2010..Our goal is to understand how SarA controls target gene and how other intracellular regulators affect SarA expression in S. aureus. ..
- The toxin-antitoxin system of Staphylococcus aureus.AMBROSE LIN YAU CHEUNG; Fiscal Year: 2010..As therapy options against multidrug resistant S. aureus are limited, our screening assays will provide the initial compounds against MazE for the development of novel antimicrobial therapy against S. aureus ..
- Binding and regulation mechanism for S aureusAmbrose Cheung; Fiscal Year: 2006..An understanding of these mechanisms will facilitate the development of novel agents that interfere with the function of the SarA family and the ensuing synthesis of cell wall adhesins and toxins. ..
- IN VIVO GENE EXPRESSION IN STAPHYLOCCUS AUREUSAmbrose Cheung; Fiscal Year: 2003..aureus infections. Our long-term goal is to examine some of these unique gene products for the development of vaccine and novel antimicrobial strategies against S. aureus. ..
- CHARACTERIZATION OF SAR/AGR INTERACTIONS IN S AUREUSAmbrose Cheung; Fiscal Year: 2004..This knowledge is indispensable if we are to design synthetic analogs to interfere with the expression of virulence genes controlled by the sar locus in the future. ..
- The role of GraRS in resistance to cationic antimicrobial peptides in S. aureusAMBROSE LIN YAU CHEUNG; Fiscal Year: 2011..We propose to define the mechanism of this resistance. Our long-term goal is to characterize these genes that confer sensitivity to cationic antimicrobial peptides so that we can design better peptide-based antibiotics in the future. ..