| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Laboratory of Human Bacterial Pathogenesis and
Research Technologies Section, Genomics Unit, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840;
Department of Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232; and
Public Health Research Institute Tuberculosis Center, International Center for Public Health, Newark, NJ 07103
In recent years, there has been a dramatic increase in the incidence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections. MW2 (pulsed-field type USA400), the prototype CA-MRSA strain, is highly virulent and has enhanced ability to evade killing by neutrophils. Although progress has been made, the molecular basis for enhanced virulence of CA-MRSA remains incompletely defined. To that end, we studied resistance of MW2 to key microbicides of human neutrophils. Hydrogen peroxide (H2O2), hypochlorous acid, and azurophilic granule proteins had significant bacteriostatic but limited staphylocidal activity toward MW2 under the conditions tested. An MW2-specific microarray revealed common changes in S. aureus gene expression following exposure to each microbicide, such as up-regulation of transcripts involved in gene regulation (e.g., saeRS and kdpDE) and stress response. Azurophilic granule proteins elicited the greatest number of changes in MW2 transcripts, including up-regulation of mRNAs encoding multiple toxins and hemolysins (e.g., hlgA, hlgB, hlgC, hla, lukS-PV, lukF-PV, sec4, and set17–26). Notably, H2O2 triggered up-regulation of transcripts related to heme/iron uptake (e.g., isdA, isdB, and isdCDEFsrtBisdG), and an isogenic isdAB-negative strain of MW2 had increased susceptibility to H2O2 (p < 0.001) and human neutrophils (p < 0.05) compared with the wild-type parental strain. These findings reveal a S. aureus survival response wherein Iron-regulated surface determinant (Isd) proteins are important for resistance to innate host defense. Collectively, the data provide an enhanced view of the mechanisms used by S. aureus to circumvent destruction by the innate immune system.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This research was supported by the Intramural Research Program of the National Institutes of Health, National Institutes of Allergy and Infectious Diseases (to F.R.D.), a research grant from Johnson & Johnson Pharmaceutical Research and Development (to B.N.K.), and a United States Public Health Service Grant (AI69233) from the National Institute of Allergy and Infectious Diseases (to E.P.S). M.L.R. is supported by a National Institutes of Health Training Grant in Mechanisms of Vascular Disease T32 HL07751.
2 Address correspondence and reprint requests to Dr. Frank R. DeLeo, Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840. E-mail address: fdeleo{at}niaid.nih.gov
3 Abbreviations used in this paper: PMN, polymorphonuclear leukocyte; ROS, reactive oxygen species; CA, community associated; MRSA, methicillin-resistant S. aureus; TSB, tryptic soy broth; TSA, tryptic soy agar; HOCl, hypochlorous acid; DPI, diphenyleneiodonium chloride; Isd, Iron-regulated surface determinant.
4 The online version of this article contains supplemental material.
Related articles in The JI:
This article has been cited by other articles:
|
|
 |
|
  J. Schwartz, K. G. Leidal, J. K. Femling, J. P. Weiss, and W. M. Nauseef Neutrophil Bleaching of GFP-Expressing Staphylococci: Probing the Intraphagosomal Fate of Individual Bacteria J. Immunol., August 15, 2009; 183(4): 2632 - 2641. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Carlson, W. M. Whitmire, D. D. Crane, L. Wicke, K. Virtaneva, D. E. Sturdevant, J. J. Kupko III, S. F. Porcella, N. Martinez-Orengo, R. A. Heinzen, et al. The Chlamydia trachomatis Plasmid Is a Transcriptional Regulator of Chromosomal Genes and a Virulence Factor Infect. Immun., June 1, 2008; 76(6): 2273 - 2283. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. R. DeLeo and M. Otto An antidote for Staphylococcus aureus pneumonia? J. Exp. Med., February 18, 2008; 205(2): 271 - 274. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
