Staphylococcus epidermidis Strategies to Avoid Killing by Human Neutrophils

PLoS Pathogens

Martin Teintze¹  Gordon Y. C. Cheung²  Michael Otto²  Shu Y. Queck³  Adeline R. Whitney³  Kevin Rigby³  Frank R. DeLeo³  Rong Wang³  Kevin R. Braughton³ 

[1] Chemistry & Biochemistry Department, Montana State University, Bozeman, Montana, United States of America;Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Bethesda, Maryland, United States of America;Laboratory of Human Bacterial Pathogenesis, National Institute of Allergy and Infectious Diseases, The National Institutes of Health, Hamilton, Montana, United States of America

关键词: Staphylococcus epidermidis;    Neutrophils;    Staphylococcus aureus;    Toxins;    Immune evasion;    Phagocytosis;    Bacterial pathogens;    Lysis (medicine);   

DOI  :  10.1371/journal.ppat.1001133

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Staphylococcus epidermidis is a leading nosocomial pathogen. In contrast to its more aggressive relative S. aureus, it causes chronic rather than acute infections. In highly virulent S. aureus, phenol-soluble modulins (PSMs) contribute significantly to immune evasion and aggressive virulence by their strong ability to lyse human neutrophils. Members of the PSM family are also produced by S. epidermidis, but their role in immune evasion is not known. Notably, strong cytolytic capacity of S. epidermidis PSMs would be at odds with the notion that S. epidermidis is a less aggressive pathogen than S. aureus, prompting us to examine the biological activities of S. epidermidis PSMs. Surprisingly, we found that S. epidermidis has the capacity to produce PSMδ, a potent leukocyte toxin, representing the first potent cytolysin to be identified in that pathogen. However, production of strongly cytolytic PSMs was low in S. epidermidis, explaining its low cytolytic potency. Interestingly, the different approaches of S. epidermidis and S. aureus to causing human disease are thus reflected by the adaptation of biological activities within one family of virulence determinants, the PSMs. Nevertheless, S. epidermidis has the capacity to evade neutrophil killing, a phenomenon we found is partly mediated by resistance mechanisms to antimicrobial peptides (AMPs), including the protease SepA, which degrades AMPs, and the AMP sensor/resistance regulator, Aps (GraRS). These findings establish a significant function of SepA and Aps in S. epidermidis immune evasion and explain in part why S. epidermidis may evade elimination by innate host defense despite the lack of cytolytic toxin expression. Our study shows that the strategy of S. epidermidis to evade elimination by human neutrophils is characterized by a passive defense approach and provides molecular evidence to support the notion that S. epidermidis is a less aggressive pathogen than S. aureus.

【 授权许可】

CC BY