Genomic characterization of colistin heteroresistance in Acinetobacter baumannii: Evidence for lpxD deletion and collateral sensitivity.

OBJECTIVES

To search for colistin heteroresistance (CHR) prevalence in Acinetobacter baumannii bloodstream isolates, and to investigate potential molecular contributors to CHR using WGS.

METHODS

A total of 267 A. baumannii isolates were recovered from bloodstream infections between January 2014 and July 2018 at a tertiary care hospital in Türkiye. Antimicrobial susceptibility to colistin was assessed using the broth microdilution method. CHR was evaluated by population analysis profiling (PAP). WGS was performed on a representative heteroresistant strain (A325) to investigate putative CHR-associated mechanisms.

RESULTS

Thirty-five isolates (13.9%) were classified as colistin-resistant. CHR was identified in 86 of 267 isolates (32.2%) using PAP. Comparative genomic analysis of the colistin-susceptible main population and the colistin-resistant subpopulation of isolate A325 revealed identical mutational profiles in known resistance-associated genes, with the exception of a partial deletion in the lpxD gene between codons 2 and 75, identified exclusively in the resistant subpopulation. Notably, tetracyclines, macrolides and aminoglycosides were fully inactive in the colistin-susceptible main population, whereas an inhibition zone around these antibiotic discs was observed with the colistin-resistant subpopulation.

CONCLUSIONS

This study demonstrates a high prevalence of both colistin resistance and CHR among A. baumannii bloodstream isolates. The identification of a partial lpxD deletion in the resistant subpopulation of the colistin-heteroresistant isolate suggests a potential contributory role of LPS-related alterations in CHR. Inverse antimicrobial activity profiles between populations highlight distinct resistance mechanisms potentially shaped by evolutionary trade-offs and collateral sensitivity.