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Rapid evolution and host immunity drive the rise and fall of carbapenem resistance during an acute Pseudomonas aeruginosa infection
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Rapid evolution and host immunity drive the rise and fall of carbapenem resistance during an acute Pseudomonas aeruginosa infection
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Journal Article
Rapid evolution and host immunity drive the rise and fall of carbapenem resistance during an acute Pseudomonas aeruginosa infection
2021
Overview
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.
Here, following a patient with severe acute
Pseudomonas aeruginosa
infection, the authors combine comprehensive isolate characterization from lung and gut samples (>100 isolates) and patient clinical data to provide insights into bacterial responses to antibiotic therapy.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 45/23
/ 631/181
/ 631/326
/ Anti-Bacterial Agents - therapeutic use
/ Bacterial Outer Membrane Proteins - genetics
/ Bacterial Proteins - genetics
/ Drug Resistance, Multiple, Bacterial - genetics
/ Efflux
/ Fitness
/ Humanities and Social Sciences
/ Humans
/ Immunity
/ Lungs
/ Membrane Transport Proteins - genetics
/ Patients
/ Pseudomonas aeruginosa - drug effects
/ Pseudomonas aeruginosa - genetics
/ Pseudomonas aeruginosa - immunology
/ Pseudomonas Infections - drug therapy
/ Pseudomonas Infections - pathology
/ Respiratory Tract Infections - diagnosis
/ Respiratory Tract Infections - drug therapy
/ Respiratory Tract Infections - microbiology
/ Science
