The highly dynamic nature of bacterial heteroresistance impairs its clinical detection.
Commun Biol
; 4(1): 521, 2021 05 05.
Article
in En
| MEDLINE
| ID: mdl-33953333
ABSTRACT
Many bacterial species and antibiotic classes exhibit heteroresistance, a phenomenon in which a susceptible bacterial isolate harbors a resistant subpopulation that can grow in the presence of an antibiotic and cause treatment failure. The resistant phenotype is often unstable and without antibiotic selection it reverts back to susceptibility. Here we studied the dynamics by which these resistant subpopulations are enriched in the presence of antibiotic and recede back to their baseline frequency in the absence of selection. An increasing understanding of this instability will allow more effective diagnostics and treatment of infections caused by heteroresistant bacteria. We show for clinical isolates of Escherichia coli and Salmonella enterica that different antibiotics at levels below the MIC of the susceptible main population can cause rapid enrichment of resistant subpopulations with increased copy number of genes that cause resistance. Modelling and growth rate measurements of bacteria with increased gene copy number in cultures and by microscopy of single-cells in a microfluidic chip show that the fitness cost of gene amplifications and their intrinsic instability drives their rapid loss in the absence of selection. Using a common antibiotic susceptibility test, we demonstrate that this test strongly underestimates the occurrence of heteroresistance in clinical isolates.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Salmonella Infections
/
Bacterial Proteins
/
Salmonella enterica
/
Drug Resistance, Multiple, Bacterial
/
Escherichia coli
/
Escherichia coli Infections
/
Anti-Bacterial Agents
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Commun Biol
Year:
2021
Document type:
Article
Affiliation country: