Rapid evolution and host immunity drive the rise and fall of carbapenem resistance during an acute Pseudomonas aeruginosa infection.

Anti-Bacterial Agents / therapeutic use Bacterial Outer Membrane Proteins / genetics Bacterial Proteins / genetics Drug Resistance, Multiple, Bacterial / genetics Humans Hydro-Lyases / genetics Membrane Transport Proteins / genetics Meropenem / therapeutic use Microbial Sensitivity Tests Middle Aged Plasmids / genetics Porins / genetics Pseudomonas Infections / drug therapy Pseudomonas aeruginosa / drug effects Respiratory Tract Infections / diagnosis Selection, Genetic / genetics Sequence Analysis, DNA Shock, Hemorrhagic / microbiology

Journal

Nature communications

ISSN: 2041-1723

Titre abrégé: Nat Commun

Pays: England

ID NLM: 101528555

Informations de publication

Date de publication:
28 04 2021

Historique:

received: 22 09 2020

accepted: 31 03 2021

entrez: 29 4 2021

pubmed: 30 4 2021

medline: 13 5 2021

Statut: epublish

Résumé

It is well established that antibiotic treatment selects for resistance, but the dynamics of this process during infections are poorly understood. Here we map the responses of Pseudomonas aeruginosa to treatment in high definition during a lung infection of a single ICU patient. Host immunity and antibiotic therapy with meropenem suppressed P. aeruginosa, but a second wave of infection emerged due to the growth of oprD and wbpM meropenem resistant mutants that evolved in situ. Selection then led to a loss of resistance by decreasing the prevalence of low fitness oprD mutants, increasing the frequency of high fitness mutants lacking the MexAB-OprM efflux pump, and decreasing the copy number of a multidrug resistance plasmid. Ultimately, host immunity suppressed wbpM mutants with high meropenem resistance and fitness. Our study highlights how natural selection and host immunity interact to drive both the rapid rise, and fall, of resistance during infection.

Identifiants

DOI: 10.1038/s41467-021-22814-9 PMID: 33911082 PMC: PMC8080559

pubmed: 33911082

doi: 10.1038/s41467-021-22814-9

pii: 10.1038/s41467-021-22814-9

pmc: PMC8080559

doi:

Substances chimiques

Anti-Bacterial Agents 0

Bacterial Outer Membrane Proteins 0

Bacterial Proteins 0

Membrane Transport Proteins 0

MexA protein, Pseudomonas aeruginosa 0

MexB protein, Pseudomonas aeruginosa 0

OprM protein, Pseudomonas aeruginosa 0

Porins 0

OprD protein, Pseudomonas aeruginosa 148412-32-2

Hydro-Lyases EC 4.2.1.-

wbpM protein, Pseudomonas aeruginosa EC 4.2.1.-

Meropenem FV9J3JU8B1

Banques de données

figshare

['10.6084/m9.figshare.14219129.v1']

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

2460

Subventions

Organisme : Wellcome Trust

ID : 106918/Z/15/Z

Pays : United Kingdom

Organisme : Wellcome Trust

ID : 203141/Z/16/Z

Pays : United Kingdom

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