In:
PLOS Biology, Public Library of Science (PLoS), Vol. 19, No. 3 ( 2021-3-10), p. e3001093-
Abstract:
Bacterial opportunistic human pathogens frequently exhibit intrinsic antibiotic tolerance and resistance, resulting in infections that can be nearly impossible to eradicate. We asked whether this recalcitrance could be driven by these organisms’ evolutionary history as environmental microbes that engage in chemical warfare. Using Pseudomonas aeruginosa as a model, we demonstrate that the self-produced antibiotic pyocyanin (PYO) activates defenses that confer collateral tolerance specifically to structurally similar synthetic clinical antibiotics. Non-PYO-producing opportunistic pathogens, such as members of the Burkholderia cepacia complex, likewise display elevated antibiotic tolerance when cocultured with PYO-producing strains. Furthermore, by widening the population bottleneck that occurs during antibiotic selection and promoting the establishment of a more diverse range of mutant lineages, PYO increases apparent rates of mutation to antibiotic resistance to a degree that can rival clinically relevant hypermutator strains. Together, these results reveal an overlooked mechanism by which opportunistic pathogens that produce natural toxins can dramatically modulate the efficacy of clinical antibiotics and the evolution of antibiotic resistance, both for themselves and other members of clinically relevant polymicrobial communities.
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3001093
DOI:
10.1371/journal.pbio.3001093.g001
DOI:
10.1371/journal.pbio.3001093.g002
DOI:
10.1371/journal.pbio.3001093.g003
DOI:
10.1371/journal.pbio.3001093.g004
DOI:
10.1371/journal.pbio.3001093.g005
DOI:
10.1371/journal.pbio.3001093.g006
DOI:
10.1371/journal.pbio.3001093.g007
DOI:
10.1371/journal.pbio.3001093.s001
DOI:
10.1371/journal.pbio.3001093.s002
DOI:
10.1371/journal.pbio.3001093.s003
DOI:
10.1371/journal.pbio.3001093.s004
DOI:
10.1371/journal.pbio.3001093.s005
DOI:
10.1371/journal.pbio.3001093.s006
DOI:
10.1371/journal.pbio.3001093.s007
DOI:
10.1371/journal.pbio.3001093.s008
DOI:
10.1371/journal.pbio.3001093.s009
DOI:
10.1371/journal.pbio.3001093.s010
DOI:
10.1371/journal.pbio.3001093.s011
DOI:
10.1371/journal.pbio.3001093.s012
DOI:
10.1371/journal.pbio.3001093.s013
DOI:
10.1371/journal.pbio.3001093.s014
DOI:
10.1371/journal.pbio.3001093.s015
DOI:
10.1371/journal.pbio.3001093.s016
DOI:
10.1371/journal.pbio.3001093.s017
DOI:
10.1371/journal.pbio.3001093.s018
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2126773-X
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