Endopeptidase-mediated beta lactam tolerance.

Abstract:

:In many bacteria, inhibition of cell wall synthesis leads to cell death and lysis. The pathways and enzymes that mediate cell lysis after exposure to cell wall-acting antibiotics (e.g. beta lactams) are incompletely understood, but the activities of enzymes that degrade the cell wall ('autolysins') are thought to be critical. Here, we report that Vibrio cholerae, the cholera pathogen, is tolerant to antibiotics targeting cell wall synthesis. In response to a wide variety of cell wall--acting antibiotics, this pathogen loses its rod shape, indicative of cell wall degradation, and becomes spherical. Genetic analyses revealed that paradoxically, V. cholerae survival via sphere formation required the activity of D,D endopeptidases, enzymes that cleave the cell wall. Other autolysins proved dispensable for this process. Our findings suggest the enzymes that mediate cell wall degradation are critical for determining bacterial cell fate--sphere formation vs. lysis--after treatment with antibiotics that target cell wall synthesis.

journal_name

PLoS Pathog

journal_title

PLoS pathogens

authors

Dörr T,Davis BM,Waldor MK

doi

10.1371/journal.ppat.1004850

subject

Has Abstract

pub_date

2015-04-17 00:00:00

pages

e1004850

issue

4

eissn

1553-7366

issn

1553-7374

pii

PPATHOGENS-D-14-03110

journal_volume

11

pub_type

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