title: 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.
authors.affiliation: Division of Infectious Diseases, Brigham and Women's Hospital and Howard Hughes Medical Institute, Boston, Massachusetts, United States of America; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Tobias
authors.initials: T
authors.lastname: Dörr
authors.affiliation: Division of Infectious Diseases, Brigham and Women's Hospital and Howard Hughes Medical Institute, Boston, Massachusetts, United States of America; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Brigid M
authors.initials: BM
authors.lastname: Davis
authors.affiliation: Division of Infectious Diseases, Brigham and Women's Hospital and Howard Hughes Medical Institute, Boston, Massachusetts, United States of America; Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Waldor
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism; D002473:Cell Wall / Q000187:drug effects; D010450:Endopeptidases / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D014734:Vibrio cholerae / Q000187:drug effects* / Q000254:growth & development*; D018440:beta-Lactam Resistance / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D010450:Endopeptidases