Ambrose L Cheung

Dartmouth Medical School, Hanover, New Hampshire, United States

Are you Ambrose L Cheung?

Claim your profile

Publications (130)627.16 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: Background. Staphylococcus aureus is the most common cause of endovascular infections. The staphylococcal accessory regulator A, sarA, is a major virulence determinant that may potentially impact MRSA persistence in such infections via its influence upon biofilm formation.Methods. Two healthcare-associated MRSA isolates from patients with persistent bacteremia and two prototypical community-acquired MRSA strains, and their respective isogenic sarA mutants were studied for in vitro: i) biofilm formation; ii) fibronectin-binding capacity; iii) autolysis; and iv) protease and nuclease activities. These assays were done in the presence or absence of sub-MIC vancomycin. In addition, these strain-pairs were compared for intrinsic virulence and responses to vancomycin therapy in experimental infective endocarditis (IE), a prototypical biofilm model.Results. All sarA mutants displayed significantly reduced biofilm formation and binding to fibronectin, but increased protease production in vitro vs. their respective parental strains. Interestingly, sub-MIC exposure to vancomycin significantly promoted biofilm formation and fibronectin-binding in parental strains, but not in sarA mutants. In addition, all sarA mutants became exquisitely sensitive to vancomycin therapy vs. their respective parental strains in the IE model.Conclusions. These observations suggest that sarA activation is important in persistent MRSA endovascular infection, potentially in the setting of biofilm formation.
    The Journal of Infectious Diseases 01/2014; · 5.85 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: In S. aureus, the low molecular weight thiol called bacillithiol (BSH), together with cognate S-transferases, is believed to be the counterpart to the glutathione system of other organisms. To explore the physiological role of BSH in S. aureus, we constructed deletion mutants of bshA (sa1291), which encodes the glycosyl transferase that catalyzes the first step of BSH biosynthesis, and fosB (SA2124), which encodes a BSH-S-transferase that confers fosfomycin resistance, in several S. aureus strains including clinical isolates. Mutation of fosB or bshA caused a 16- to 60-fold reduction in fosfomycin resistance in these S. aureus strains. HPLC analysis, which quantified thiol extracts, revealed some variability in the amounts of BSH present across S. aureus strains. Deletion of fosB leads to a decrease in BSH levels. The fosB and bshA mutants of COL and a USA300 isolate, upon further characterization, were found to be sensitive to H2O2 and exhibited decreased NADPH levels vs. the isogenic parents. Microarray analyses of COL and the isogenic bshA mutant revealed increased expression of genes involved in staphyloxanthin synthesis in the bshA mutant relative to COL under thiol stress. However, the bshA mutant of COL demonstrated decreased survival when compared to that of the parent in human whole blood survival assays; likewise, the naturally BSH-deficient strain SH1000 survived less well than its BSH-producing isogenic counterpart. Thus, the survival of S. aureus under oxidative stress is facilitated by BSH, possibly via a FosB-mediated mechanism, independent of its capability to produce staphyloxanthin.
    Infection and immunity 10/2013; · 4.21 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) frequently causes skin and soft-tissue infections, including impetigo, cellulitis, folliculitis, and infected wounds and ulcers. Uncomplicated CA-MRSA skin infections are typically managed in an outpatient setting with oral and topical antibiotics and/or incision and drainage whereas complicated skin infections often require hospitalization, intravenous antibiotics, and sometimes surgery. The aim of this study was to develop a mouse model of CA-MRSA wound infection to compare the efficacy of commonly used systemic and topical antibiotics. A bioluminescent USA300 CA-MRSA strain was inoculated into full-thickness scalpel wounds on the backs of mice and digital photography/image analysis and in vivo bioluminescence imaging were used to measure wound healing and the bacterial burden. Subcutaneous vancomycin, daptomycin and linezolid similarly reduced the lesion sizes and bacterial burden. Oral linezolid, clindamycin and doxycycline all decreased the lesion sizes and bacterial burden. Oral trimethoprim/sulfamethoxazole decreased the bacterial burden but did not decrease the lesion size. Topical mupirocin and retapamulin ointments both reduced the bacterial burden. However, the petrolatum vehicle ointment for retapamulin, but not the polyethylene glycol vehicle ointment for mupirocin, promoted wound healing and initially increased the bacterial burden. Finally, in type 2 diabetic mice, subcutaneous linezolid and daptomycin had the most rapid therapeutic effect compared with vancomycin. Taken together, this mouse model of CA-MRSA wound infection, which utilizes in vivo bioluminescence imaging to monitor the bacterial burden, represents an alternative method to evaluate the preclinical in vivo efficacy of systemic and topical antimicrobial agents.
    Antimicrobial Agents and Chemotherapy 12/2012; · 4.57 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Neutrophil abscess formation is critical in innate immunity against many pathogens. Here, the mechanism of neutrophil abscess formation was investigated using a mouse model of Staphylococcus aureus cutaneous infection. Gene expression analysis and in vivo multispectral noninvasive imaging during the S. aureus infection revealed a strong functional and temporal association between neutrophil recruitment and IL-1β/IL-1R activation. Unexpectedly, neutrophils but not monocytes/macrophages or other MHCII-expressing antigen presenting cells were the predominant source of IL-1β at the site of infection. Furthermore, neutrophil-derived IL-1β was essential for host defense since adoptive transfer of IL-1β-expressing neutrophils was sufficient to restore the impaired neutrophil abscess formation in S. aureus-infected IL-1β-deficient mice. S. aureus-induced IL-1β production by neutrophils required TLR2, NOD2, FPR1 and the ASC/NLRP3 inflammasome in an α-toxin-dependent mechanism. Taken together, IL-1β and neutrophil abscess formation during an infection are functionally, temporally and spatially linked as a consequence of direct IL-1β production by neutrophils.
    PLoS Pathogens 11/2012; 8(11):e1003047. · 8.14 Impact Factor
  • Ambrose Cheung, Bertrand Duclos
    The Journal of Infectious Diseases 04/2012; 205(11):1625-7. · 5.85 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: Whole-genome sequence comparison of Staphylococcus aureus strain RN4220ΔmutS, a variant of strain RN4220 carrying an insertion in the mutS gene, and its parent strain S. aureus NCTC 8325 identified variations in the nucleic acid sequence between both strains. Some of these changes concerned proteins which are part of the ribosome (RpmF, RpsB), process ribosomal RNA (RimM), are involved in cell wall biosynthesis (EzrA, MurA), or possess chaperone functions (GroEL) and therefore might compromise the fitness of the affected strain. Resequencing of these genes in S. aureus NCTC 8325 revealed that the sequence variations represent errors in the original S. aureus NCTC 8325 genome sequence and do not constitute mutations in S. aureus RN4220 or RN4220ΔmutS. In correlation with these results, growth experiments showed that the fitness of S. aureus RN4220 is comparable to that of S. aureus NCTC 8325.
    International journal of medical microbiology: IJMM 03/2012; 302(2):84-7. · 4.54 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: The two-component regulatory system, GraRS, appears to be involved in staphylococcal responses to cationic antimicrobial peptides (CAPs). However, the mechanism(s) by which GraRS is induced, regulated, and modulated remain undefined. In this study, we used two well-characterized MRSA strains (Mu50 and COL) and their respective mutants of graR and vraG (encoding the ABC transporter-dependent efflux pump immediately downstream of graRS), and show that (i) the expression of two key determinants of net positive surface charge (mprF and dlt) is dependent on the cotranscription of both graR and vraG, (ii) reduced expression of mprF and dlt in graR mutants was phenotypically associated with reduced surface-positive charge, (iii) this net reduction in surface-positive charge in graR and vraG mutants, in turn, correlated with enhanced killing by a range of CAPs of diverse structure and origin, including those from mammalian platelets (tPMPs) and neutrophils (hNP-1) and from bacteria (polymyxin B), and (iv) the synthesis and translocation of membrane lysyl-phosphatidylglycerol (an mprF-dependent function) was substantially lower in graR and vraG mutants than in parental strains. Importantly, the inducibility of mprF and dlt transcription via the graRS-vraFG pathway was selective, with induction by sublethal exposure to the CAPs, RP-1 (platelets), and polymyxin B, but not by other cationic molecules (hNP-1, vancomycin, gentamicin, or calcium-daptomycin). Although graR regulates expression of vraG, the expression of graR was codependent on an intact downstream vraG locus. Collectively, these data support an important role of the graRS and vraFG loci in the sensing of and response to specific CAPs involved in innate host defenses.
    Infection and immunity 01/2012; 80(1):74-81. · 4.21 Impact Factor
  • Source
    Guido Memmi, Dhanalakshmi R Nair, Ambrose Cheung
    [show abstract] [hide abstract]
    ABSTRACT: Autolysis plays an essential role in bacterial cell division and lysis with β-lactam antibiotics. Accordingly, the expression of autolysins is tightly regulated by several endogenous regulators, including ArlRS, a two component regulatory system that has been shown to negatively regulate autolysis in methicillin-sensitive Staphylococcus aureus (MSSA) strains. In this study, we found that inactivation of arlRS does not play a role in autolysis of methicillin-resistant S. aureus (MRSA) strains, such as community-acquired (CA)-MRSA strains USA300 and MW2 or the hospital-acquired (HA)-MRSA strain COL. This contrasts with MSSA strains, including Newman, SH1000, RN6390, and 8325-4, where autolysis is affected by ArlRS. We further demonstrated that the striking difference in the roles of arlRS between MSSA and MRSA strains is not due to the methicillin resistance determinant mecA. Among known autolysins and their regulators, we found that arlRS represses lytN, while no effect was seen on atl, lytM, and lytH expression in both CA- and HA-MRSA strains. Transcriptional-fusion assays showed that the agr transcripts, RNAII and RNAIII, were significantly more downregulated in the arlRS mutant of MW2 than the MSSA strain Newman. Importantly, provision of agr RNAIII in trans to the MW2 arlRS mutant via a multicopy plasmid induced autolysis in this MRSA strain. 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.
    Journal of bacteriology 12/2011; 194(4):759-67. · 3.94 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: The agr locus of Staphylococcus aureus is composed of two divergent transcripts (RNAII and RNAIII) driven by the P2 and P3 promoters. The P2-P3 intergenic region comprises the SarA/SarR binding sites and the four AgrA boxes to which AgrA binds. We reported here the role of AgrA, SarA, and SarR on agr P2 and P3 transcription. Using real-time reverse transcription (RT)-PCR and promoter fusion studies with selected single, double, triple, and complemented mutants, we showed that AgrA is indispensable to agr P2 and P3 transcription, whereas SarA activates and SarR represses P2 transcription. In vitro runoff transcription assays revealed that AgrA alone promoted transcription from the agr P2 promoter, with SarA enhancing it and SarR inhibiting agr P2 transcription in the presence of AgrA or with SarA and AgrA. Electrophoretic mobility shift assay (EMSA) analysis disclosed that SarR binds more avidly to the agr promoter than SarA and displaces SarA from the agr promoter. Additionally, SarA and AgrA bend the agr P2 promoter, whereas SarR does not. Collectively, these data indicated that AgrA activates agr P2 and P3 promoters while SarA activates the P2 promoter, presumably via bending of promoter DNA to bring together AgrA dimers to facilitate engagement of RNA polymerase (RNAP) to initiate transcription.
    Journal of bacteriology 09/2011; 193(21):6020-31. · 3.94 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Post-arthroplasty infections are a devastating problem in orthopaedic surgery. While acute infections can be treated with a single stage washout and liner exchange, chronic infections lead to multiple reoperations, prolonged antibiotic courses, extended disability, and worse clinical outcomes. Unlike previous mouse models that studied an acute infection, this work aimed to develop a model of a chronic post-arthroplasty infection. To achieve this, a stainless steel implant in the knee joints of mice was inoculated with a bioluminescent Staphylococcus aureus strain (1 × 10(2) -1 × 10(4) colony forming units, CFUs) and in vivo imaging was used to monitor the bacterial burden for 42 days. Four different S. aureus strains were compared in which the bioluminescent construct was integrated in an antibiotic selection plasmid (ALC2906), the bacterial chromosome (Xen29 and Xen40), or a stable plasmid (Xen36). ALC2906 had increased bioluminescent signals through day 10, after which the signals became undetectable. In contrast, Xen29, Xen40, and Xen36 had increased bioluminescent signals through 42 days with the highest signals observed with Xen36. ALC2906, Xen29, and Xen40 induced significantly more inflammation than Xen36 as measured by in vivo enhanced green fluorescence protein (EGFP)-neutrophil flourescence of LysEGFP mice. All four strains induced comparable biofilm formation as determined by variable-pressure scanning electron microscopy. Using a titanium implant, Xen36 had higher in vivo bioluminescence signals than Xen40 but had similar biofilm formation and adherent bacteria. In conclusion, Xen29, Xen40, and especially Xen36, which had stable bioluminescent constructs, are feasible for long-term in vivo monitoring of bacterial burden and biofilm formation to study chronic post-arthroplasty infections and potential antimicrobial interventions.
    Journal of Orthopaedic Research 08/2011; 30(3):335-40. · 2.88 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: One of the virulence factors required by Staphylococcus aureus at the early stages of infection is Eap, a secreted adhesin that binds many host proteins and is upregulated by the two-component regulatory system saeRS. The S. aureus Newman strain harbors a mutation in saeS that is thought to be responsible for the high level of Eap expression in this strain. This study was designed to ascertain whether salicylic acid (SAL) affects the expression of Eap and the internalization of S. aureus into epithelial cells. The strain Newman treated with SAL exhibited increased levels of eap transcription and protein expression. Furthermore, SAL treatment increased the eap promoter activity. SAL treatment enhanced Eap expression in the Newman and in other S. aureus strains that do not carry the mutation in saeS. Internalization of S. aureus eap and sae mutants into the MAC-T epithelial cells was significantly decreased compared with the wild-type counterparts. In conclusion, we demonstrated that a low concentration of SAL increased S. aureus Eap expression possibly due to enhancement of sae. SAL may create the conditions for S. aureus persistence in the host, not only by decreasing the capsular polysaccharide expression as shown before, but also by enhancing Eap expression.
    Microbes and Infection 06/2011; 13(12-13):1073-80. · 2.92 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: In this study, we investigated the interactions of Staphylococcus aureus with mast cells, which are multifunctional sentinels lining the surfaces of the body. We found that bone marrow-derived murine mast cells (BMMC) exerted a powerful phagocytosis-independent antimicrobial activity against S. aureus. Both the release of extracellular traps as well as discharge of antimicrobial compounds were the mechanisms used by the BMMC to kill extracellular S. aureus. This was accompanied by the secretion of mediators such as TNF-α involved in the recruitment of effector cells. Interestingly, S. aureus subverted the extracellular antimicrobial activity of the BMMC by internalizing within these cells. S. aureus was also capable to internalize within human mast cells (HMC-1) and within murine skin mast cells during in vivo infection. Bacteria internalization was, at least in part, mediated by the α5β1 integrins expressed on the surface of the mast cell. In the intracellular milieu, the bacterium survived and persisted by increasing the cell wall thickness and by gaining access into the mast cell cytosol. The expression of α-hemolysin was essential for staphylococci intracellular persistence. By hiding within the long-life mast cells, staphylococci not only avoid clearance but also establish an infection reservoir that could contribute to chronic carriage.
    Journal of Innate Immunity 06/2011; 3(5):495-507. · 4.46 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: mazEF modules encode toxin-antitoxin pairs that are involved in the bacterial stress response through controlled and specific degradation of mRNA. Staphylococcus aureus MazF and MazE constitute a unique toxin-antitoxin module under regulation of the sigB operon. A MazF-type mRNA interferase is combined with an antitoxin of unknown fold. Crystals of S. aureus MazF (SaMazF) were grown in space group P2(1)2(1)2(1). The crystals diffracted to 2.1 Å resolution and are likely to contain two SaMazF dimers in the asymmetric unit.
    Acta Crystallographica Section F Structural Biology and Crystallization Communications 03/2011; 67(Pt 3):386-9. · 0.55 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Staphylococcus aureus RN4220, a cloning intermediate, is sometimes used in virulence, resistance, and metabolic studies. 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.
    Journal of bacteriology 03/2011; 193(9):2332-5. · 3.94 Impact Factor
  • [show abstract] [hide abstract]
    ABSTRACT: MazF proteins are ribonucleases that cleave mRNA with high sequence-specificity as part of bacterial stress response and that are neutralized by the action of the corresponding antitoxin MazE. Prolonged activation of the toxin MazF leads to cell death. Several mazEF modules from gram-negative bacteria have been characterized in terms of catalytic activity, auto-regulation mechanism and structure, but less is known about their distant relatives found in gram-positive organisms. Currently, no solution NMR structure is available for any wild-type MazF toxin. Here we report the (1)H, (15)N and (13)C backbone and side-chain chemical shift assignments of this toxin from the pathogen bacterium Staphylococcus aureus. The BMRB accession number is 17288.
    Biomolecular NMR Assignments 01/2011; 5(2):157-60. · 0.64 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Staphylococcus aureus skin infections represent a significant public health threat because of the emergence of antibiotic-resistant strains such as methicillin-resistant S. aureus (MRSA). As greater understanding of protective immune responses and more effective antimicrobial therapies are needed, a S. aureus skin wound infection model was developed in which full-thickness scalpel cuts on the backs of mice were infected with a bioluminescent S. aureus (methicillin sensitive) or USA300 community-acquired MRSA strain and in vivo imaging was used to noninvasively monitor the bacterial burden. In addition, the infection-induced inflammatory response was quantified using in vivo fluorescence imaging of LysEGFP mice. Using this model, we found that both IL-1α and IL-1β contributed to host defense during a wound infection, whereas IL-1β was more critical during an intradermal S. aureus infection. Furthermore, treatment of a USA300 MRSA skin infection with retapamulin ointment resulted in up to 85-fold reduction in bacterial burden and a 53% decrease in infection-induced inflammation. In contrast, mupirocin ointment had minimal clinical activity against this USA300 strain, resulting in only a 2-fold reduction in bacterial burden. Taken together, this S. aureus wound infection model provides a valuable preclinical screening method to investigate cutaneous immune responses and the efficacy of topical antimicrobial therapies.
    Journal of Investigative Dermatology 12/2010; 131(4):907-15. · 6.19 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: The Staphylococcus aureus SarA global regulator controls the expression of numerous virulence genes, often in conjunction with the agr quorum-sensing system and its effector RNA, RNAIII. In the present study, we have examined the role of both SarA and RNAIII on the regulation of the promoter of tst, encoding staphylococcal superantigen toxic shock syndrome toxin 1 (TSST-1). In vitro DNA-protein interaction studies with purified SarA using gel shift and DNase I protection assays revealed one strong SarA binding site and evidence for a weaker site nearby within the minimal 400-bp promoter region upstream of tst. In vivo analysis of tst promoter activation using a p(tst)-luxAB reporter inserted in the chromosome revealed partial but not complete loss of tst expression in a Δhld-RNAIII strain. In contrast, disruption of sarA abrogated tst expression. No significant tst expression was found for the double Δhld-RNAIII-ΔsarA mutant. Introduction of a plasmid containing cloned hld-RNAIII driven by a non-agr-dependent promoter, p(HU), into isogenic parental wild-type or ΔsarA strains showed comparable levels of RNAIII detected by quantitative reverse transcription-PCR (qRT-PCR) but a two-log(10) reduction in p(tst)-luxAB reporter expression in the ΔsarA strain, arguing that RNAIII levels alone are not strictly determinant for tst expression. Collectively, our results indicate that SarA binds directly to the tst promoter and that SarA plays a significant and direct role in the expression of tst.
    Journal of bacteriology 11/2010; 192(22):6077-85. · 3.94 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: The expression of virulence factors in Staphylococcus aureus is tightly coordinated by a vast network of regulatory molecules. In this report, we characterize a genetic locus unique to staphylococci called rsr that has a role in repressing two key virulence regulators, sarR and agr. Using strain SH1000, we showed that the transcription of virulence effectors, such as hla, sspA, and spa, is altered in an rsr mutant in a way consistent with agr upregulation. Analysis of RNAIII expression of the agr locus in rsr and rsr-sarR mutants indicated that rsr likely contributes to agr expression independently of SarR. We also provide evidence using a murine model of S. aureus skin infection that the effects mediated by rsr reduce disease progression.
    Infection and immunity 10/2010; 78(10):4384-91. · 4.21 Impact Factor
  • Source
    Sandeep Tamber, Joseph Schwartzman, Ambrose L Cheung
    [show abstract] [hide abstract]
    ABSTRACT: The regulation of cellular processes by eukaryote-like serine/threonine kinases is widespread in bacteria. In the last 2 years, several studies have examined the role of serine/threonine kinases in Staphylococcus aureus on cell wall metabolism, autolysis, and virulence, mostly in S. aureus laboratory isolates in the 8325-4 lineage. In this study, we showed that the pknB gene (also called stk1) of methicillin-resistant S. aureus (MRSA) strain COL and the community-acquired MRSA (CA-MRSA) strain USA300 is involved in cell wall metabolism, with the pknB mutant exhibiting enhanced sensitivity to beta-lactam antibiotics but not to other classes of antibiotics, including aminoglycosides, ciprofloxacin, bactrim, and other types of cell wall-active agents (e.g., vancomycin and bacitracin). Additionally, the pknB mutant of USA300 was found to be more resistant to Triton X-100-induced autolysis and also to lysis by lysostaphin. We also showed that pknB is a positive regulator of sigB activity, resulting in compromise in its response to heat and oxidative stresses. In association with reduced sigB activity, the expression levels of RNAII and RNAIII of agr and the downstream effector hla are upregulated while spa expression is downmodulated in the pknB mutant compared to the level in the parent. Consistent with an enhanced agr response in vitro, virulence studies of the pknB mutant of USA300 in a murine cutaneous model of infection showed that the mutant was more virulent than the parental strain. Collectively, our results have linked the pknB gene in CA-MRSA to antibiotic resistance, sigB activity, and virulence and have highlighted important differences in pknB phenotypes (virulence and sigB activity) between laboratory isolates and the prototypic CA-MRSA strain USA300.
    Infection and immunity 08/2010; 78(8):3637-46. · 4.21 Impact Factor
  • Source
    [show abstract] [hide abstract]
    ABSTRACT: Staphylococcus aureus is the most common cause of skin and soft tissue infections, and rapidly emerging antibiotic-resistant strains are creating a serious public health concern. If immune-based therapies are to be an alternative to antibiotics, greater understanding is needed of the protective immune response against S. aureus infection in the skin. Although neutrophil recruitment is required for immunity against S. aureus, a role for T cells has been suggested. Here, we used a mouse model of S. aureus cutaneous infection to investigate the contribution of T cells to host defense. We found that mice deficient in gammadelta but not alphabeta T cells had substantially larger skin lesions with higher bacterial counts and impaired neutrophil recruitment compared with WT mice. This neutrophil recruitment was dependent upon epidermal Vgamma5+ gammadelta T cell production of IL-17, but not IL-21 and IL-22. Furthermore, IL-17 induction required IL-1, TLR2, and IL-23 and was critical for host defense, since IL-17R-deficient mice had a phenotype similar to that of gammadelta T cell-deficient mice. Importantly, gammadelta T cell-deficient mice inoculated with S. aureus and treated with a single dose of recombinant IL-17 had lesion sizes and bacterial counts resembling those of WT mice, demonstrating that IL-17 could restore the impaired immunity in these mice. Our study defines what we believe to be a novel role for IL-17-producing epidermal gammadelta T cells in innate immunity against S. aureus cutaneous infection.
    The Journal of clinical investigation 04/2010; 120(5):1762-73. · 15.39 Impact Factor

Publication Stats

5k Citations
627.16 Total Impact Points


  • 2001–2013
    • Dartmouth Medical School
      • Department of Microbiology and Immunology
      Hanover, New Hampshire, United States
  • 2004–2012
    • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
      • Department of Medicine
      Torrance, California, United States
  • 1989–2012
    • University of California, Los Angeles
      • • Department of Medicine
      • • Department of Orthopaedic Surgery
      • • Division of Dermatology
      • • Division of Infectious Diseases
      • • Department of Pediatrics
      Los Angeles, CA, United States
  • 2010
    • Cornell University
      Ithaca, New York, United States
  • 2008–2010
    • Dartmouth–Hitchcock Medical Center
      Lebanon, New Hampshire, United States
  • 2009
    • University of New Mexico
      • Department of Molecular Genetics/Microbiology
      Albuquerque, NM, United States
  • 2005–2009
    • Valencian Institute for Agricultural Research
      • Centro de Investigación en Tecnología Animal (CITA)
      Valenza, Valencia, Spain
    • University CEU Cardenal Herrera
      Valenza, Valencia, Spain
  • 2006–2008
    • University of South Dakota
      • Division of Basic Biomedical Sciences
      Vermillion, South Dakota, United States
    • Texas Tech University Health Sciences Center
      • Department of Medicine
      Lubbock, TX, United States
    • Children's Hospital Los Angeles
      Los Angeles, California, United States
  • 2000
    • CUNY Graduate Center
      New York City, New York, United States
  • 1988–2000
    • The Rockefeller University
      • Laboratory of Bacterial Pathogenesis and Immunology
      New York City, NY, United States
  • 1997
    • Harbor-UCLA Medical Center
      Torrance, California, United States
    • Charles R. Drew University of Medicine and Science
      Los Angeles, California, United States
    • University of California, San Francisco
      • Division of Hospital Medicine
      San Francisco, CA, United States