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

Autor:	Salamaga B; Krebs Institute, University of Sheffield, Sheffield, United Kingdom.; Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, United Kingdom., Prajsnar TK; Krebs Institute, University of Sheffield, Sheffield, United Kingdom.; Department of Infection and Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom.; The Bateson Centre, University of Sheffield, Sheffield, United Kingdom., Jareño-Martinez A; Krebs Institute, University of Sheffield, Sheffield, United Kingdom.; Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, United Kingdom., Willemse J; Institute of Biology, Leiden University, Leiden, The Netherlands., Bewley MA; Krebs Institute, University of Sheffield, Sheffield, United Kingdom.; Department of Infection and Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom., Chau F; INSERM, UMR 1137, Infection, Antimicrobiens Modelisation, Evolution (IAME), Université Paris Diderot, Sorbonne Paris cité, Paris, France., Ben Belkacem T; Krebs Institute, University of Sheffield, Sheffield, United Kingdom.; Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, United Kingdom., Meijer AH; Institute of Biology, Leiden University, Leiden, The Netherlands., Dockrell DH; Krebs Institute, University of Sheffield, Sheffield, United Kingdom.; Department of Infection and Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom., Renshaw SA; Krebs Institute, University of Sheffield, Sheffield, United Kingdom.; Department of Infection and Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom.; The Bateson Centre, University of Sheffield, Sheffield, United Kingdom., Mesnage S; Krebs Institute, University of Sheffield, Sheffield, United Kingdom.; Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield, United Kingdom.
Jazyk:	angličtina
Zdroj:	PLoS pathogens [PLoS Pathog] 2017 Jul 24; Vol. 13 (7), pp. e1006526. Date of Electronic Publication: 2017 Jul 24 (Print Publication: 2017).
DOI:	10.1371/journal.ppat.1006526
Abstrakt:	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.
Databáze:	MEDLINE
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