PUBLICATION

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

Authors
Salamaga, B., Prajsnar, T.K., Jareño-Martinez, A., Willemse, J., Bewley, M.A., Chau, F., Ben Belkacem, T., Meijer, A.H., Dockrell, D.H., Renshaw, S.A., Mesnage, S.
ID
ZDB-PUB-170726-6
Date
2017
Source
PLoS pathogens   13: e1006526 (Journal)
Registered Authors
Meijer, Annemarie H., Prajsnar, Thomasz, Renshaw, Steve A.
Keywords
Enterococcus faecalis, Phagocytes, Recombinant proteins, Zebrafish, Phagocytosis, Enterococcus infections, Glycosylation, Flow cytometry
MeSH Terms
  • Animals
  • Bacterial Proteins/genetics
  • Bacterial Proteins/metabolism
  • Cell Division
  • Cell Wall/genetics
  • Cell Wall/metabolism*
  • Enterococcus faecalis/cytology*
  • Enterococcus faecalis/enzymology
  • Enterococcus faecalis/genetics
  • Enterococcus faecalis/pathogenicity*
  • Gram-Positive Bacterial Infections/microbiology*
  • Humans
  • N-Acetylmuramoyl-L-alanine Amidase/genetics
  • N-Acetylmuramoyl-L-alanine Amidase/metabolism
  • Virulence
  • Zebrafish/microbiology
PubMed
28742152 Full text @ PLoS Pathog.
Abstract
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping