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PMID: 19649313 Published · ppublish English Journal Article Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

Mobile genetic element-encoded cytolysin connects virulence to methicillin resistance in MRSA.

PLoS pathogens ·Vol. 5 ·No. 7 ·2009-07-00 ·Pages e1000533

Queck SY, Khan BA, Wang R, Bach TH, Kretschmer D, Chen L, Kreiswirth BN, Peschel A, Deleo FR, Otto M

Abstract

Bacterial virulence and antibiotic resistance have a significant influence on disease severity and treatment options during bacterial infections. Frequently, the underlying genetic determinants are encoded on mobile genetic elements (MGEs). In the leading human pathogen Staphylococcus aureus, MGEs that contain antibiotic resistance genes commonly do not contain genes for virulence determinants. The phenol-soluble modulins (PSMs) are staphylococcal cytolytic toxins with a crucial role in immune evasion. While all known PSMs are core genome-encoded, we here describe a previously unidentified psm gene, psm-mec, within the staphylococcal methicillin resistance-encoding MGE SCCmec. PSM-mec was strongly expressed in many strains and showed the physico-chemical, pro-inflammatory, and cytolytic characteristics typical of PSMs. Notably, in an S. aureus strain with low production of core genome-encoded PSMs, expression of PSM-mec had a significant impact on immune evasion and disease. In addition to providing high-level resistance to methicillin, acquisition of SCCmec elements encoding PSM-mec by horizontal gene transfer may therefore contribute to staphylococcal virulence by substituting for the lack of expression of core genome-encoded PSMs. Thus, our study reveals a previously unknown role of methicillin resistance clusters in staphylococcal pathogenesis and shows that important virulence and antibiotic resistance determinants may be combined in staphylococcal MGEs.

MeSH Terms
Animals Bacterial Proteins/genetics,immunology,metabolism Bacterial Toxins/genetics,immunology,metabolism Base Sequence Biofilms/growth & development Chemical Phenomena Cysteine/metabolism Disease Models, Animal Hemolysis Humans Inflammation/immunology,microbiology Interspersed Repetitive Sequences Methicillin-Resistant Staphylococcus aureus/genetics,metabolism,pathogenicity Mice Molecular Sequence Data Neutrophils/cytology,microbiology Penicillin-Binding Proteins Perforin/genetics,metabolism Staphylococcus epidermidis/genetics,metabolism,pathogenicity
Chemicals
Bacterial Proteins Bacterial Toxins Penicillin-Binding Proteins mecA protein, Staphylococcus aureus staphylococcal delta toxin Perforin Cysteine
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Queck Shu Y
Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA.
Khan Burhan A
Wang Rong
Bach Thanh-Huy L
Kretschmer Dorothee
Chen Liang
Kreiswirth Barry N
Peschel Andreas
Deleo Frank R
Otto Michael
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Article Info
Journal
PLoS pathogens
Abbr.
PLoS Pathog
ISSN
1553-7374
DOI
10.1371/journal.ppat.1000533
Published
2009-07-00
Epub
2009-00-31
Pages
e1000533
Language
English
Region
United States
NLM ID
101238921
PMCID
PMC2712073
Subset
IM
Grants
Intramural NIH HHS · United States
External Links
PubMed source DOI: 10.1371/journal.ppat.1000533 PMC Full Text View journal details
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