Mobile Genetic Element-Encoded Cytolysin Connects Virulence to Methicillin Resistance in MRSA

PLoS Pathogens

Andreas Peschel¹  Dorothee Kretschmer¹  Shu Y. Queck²  Michael Otto²  Frank R. DeLeo²  Rong Wang²  Thanh-Huy L. Bach²  Burhan A. Khan²  Liang Chen³  Barry N. Kreiswirth³ 

[1] Cellular and Molecular Microbiology Unit, Medical Microbiology and Hygiene Department, University of Tübingen, Tübingen, Germany;Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, Maryland, and Hamilton, Montana, United States of America;Public Health Research Institute, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, United States of America

关键词: Staphylococcus aureus;    Neutrophils;    Methicillin-resistant Staphylococcus aureus;    Staphylococcus epidermidis;    Antibiotic resistance;    Staphylococcus;    Toxins;    Mobile genetic elements;   

DOI  :  10.1371/journal.ppat.1000533

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY