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


SANCAK B., KIRBAŞ E., ARI O., DURMAZ R.

Journal of Antimicrobial Chemotherapy, cilt.81, sa.4, 2026 (SCI-Expanded, Scopus) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 81 Sayı: 4
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1093/jac/dkag076
  • Dergi Adı: Journal of Antimicrobial Chemotherapy
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, CINAHL, EMBASE, Environment Index
  • Eskişehir Osmangazi Üniversitesi Adresli: Evet

Özet

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 colistinresistant 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 colistinheteroresistant 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.