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.