Identification of Evolutionary Trade-Offs Associated With High-Level Colistin Resistance in Acinetobacter baumannii

Area of Science:

• Microbiology
• Bacterial Genetics
• Drug Resistance

Background:

• Colistin (COL) is a last-resort antibiotic against Gram-negative bacteria.
• Acinetobacter baumannii is a priority pathogen with increasing antibiotic resistance.
• Mechanisms of COL resistance include LPS modification and efflux, but trade-offs are poorly understood.

Purpose of the Study:

• To investigate the adaptive evolution of extreme colistin resistance in Acinetobacter baumannii.
• To characterize the phenotypic and genotypic changes associated with colistin resistance.
• To identify potential collateral sensitivities in colistin-resistant strains.

Main Methods:

• Adaptive laboratory evolution of Acinetobacter baumannii ATCC19606 to high colistin concentrations.
• Systemic phenotypic characterization, including biofilm formation and fitness assays.
• Antibiotic susceptibility profiling and whole-genome sequencing of evolved mutants.
• Phenotypic characterization of clinical colistin-resistant isolates.

Main Results:

• Evolved colistin-resistant mutants exhibited hyperbiofilm formation and significantly reduced bacterial fitness.
• Collateral sensitivity was observed against vancomycin and fosfomycin.
• Whole-genome sequencing identified mutations associated with colistin resistance.
• Clinical isolates showed resistance mechanisms similar to evolved strains, with no detected mcr-genes.

Conclusions:

• Colistin resistance evolution in Acinetobacter baumannii is accompanied by significant fitness costs and altered phenotypes.
• Collateral sensitivity presents potential alternative treatment options.
• Resistance mechanisms in clinical isolates may involve chromosomal alterations rather than plasmid-mediated mcr-genes.