Bacterial size matters: Multiple mechanisms controlling septum cleavage and diplococcus formation are critical for the virulence of the opportunistic pathogen Enterococcus faecalis

PLoS Pathogens

Joost Willemse¹  Stephen A. Renshaw¹  Tomasz K. Prajsnar²  Tassadit Ben Belkacem²  Stéphane Mesnage³  Annemarie H. Meijer⁴  Bartłomiej Salamaga⁵  David H. Dockrell⁵  Ana Jareño-Martinez⁵  Françoise Chau⁵  Martin A. Bewley⁶ 

[1] Department of Infection and Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom;Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, United Kingdom;INSERM, UMR 1137, Infection, Antimicrobiens Modelisation, Evolution (IAME), Université Paris Diderot, Sorbonne Paris cité, Paris, France;Institute of Biology, Leiden University, Leiden, The Netherlands;Krebs Institute, University of Sheffield, Sheffield, United Kingdom;The Bateson Centre, University of Sheffield, Sheffield, United Kingdom

关键词: Enterococcus faecalis;    Phagocytes;    Zebrafish;    Phagocytosis;    Recombinant proteins;    Enterococcus infections;    Glycosylation;    Flow cytometry;   

DOI  :  10.1371/journal.ppat.1006526

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Enterococcus faecalis is an opportunistic pathogen frequently isolated in clinical settings. This organism is intrinsically resistant to several clinically relevant antibiotics and can transfer resistance to other pathogens. Although E. faecalis has emerged as a major nosocomial pathogen, the mechanisms underlying the virulence of this organism remain elusive. We studied the regulation of daughter cell separation during growth and explored the impact of this process on pathogenesis. We demonstrate that the activity of the AtlA peptidoglycan hydrolase, an enzyme dedicated to septum cleavage, is controlled by several mechanisms, including glycosylation and recognition of the peptidoglycan substrate. We show that the long cell chains of E. faecalis mutants are more susceptible to phagocytosis and are no longer able to cause lethality in the zebrafish model of infection. Altogether, this work indicates that control of cell separation during division underpins the pathogenesis of E. faecalis infections and represents a novel enterococcal virulence factor. We propose that inhibition of septum cleavage during division represents an attractive therapeutic strategy to control infections.

【 授权许可】

CC BY