3 years ago

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

Martin A. Bewley, Ana Jareño-Martinez, Bartłomiej Salamaga, Tassadit Ben Belkacem, Joost Willemse, Françoise Chau, Annemarie H. Meijer, Tomasz K. Prajsnar, Stéphane Mesnage, Stephen A. Renshaw, David H. Dockrell

by Bartłomiej Salamaga, Tomasz K. Prajsnar, Ana Jareño-Martinez, Joost Willemse, Martin A. Bewley, Françoise Chau, Tassadit Ben Belkacem, Annemarie H. Meijer, David H. Dockrell, Stephen A. Renshaw, Stéphane Mesnage

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.

Publisher URL: http://journals.plos.org/plosone/article

DOI: 10.1371/journal.ppat.1006526

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