Trajectory of genetic alterations associated with colistin resistance in Acinetobacter baumannii during an in-hospital outbreak of infection

Abstract

Background As carbapenem-resistant Acinetobacter baumannii is dominant in clinical settings, the old polymyxin antibiotic colistin has been revived as a therapeutic option. The development of colistin resistance during treatment is becoming a growing concern. Objectives To access low- to mid-level colistin-resistant A. baumannii blood isolates recovered from an outbreak in a tertiary care hospital from a national antimicrobial surveillance study. Methods The entire bacterial genome was sequenced through long-read sequencing methodology. Quantitative RT–PCR was carried out to determine the level of gene expression. Relative growth rates were determined to estimate fitness costs of each isolate caused by the genetic alterations. Results The A. baumannii isolates belonged to global clone 2 harbouring two intrinsic phosphoethanolamine transferases. Cumulative alterations continuing the colistin resistance were observed. PmrC overproduction caused by the PmrBA226T alteration was identified in A. baumannii isolates with low-level colistin resistance and an additional PmrCR109H substitution led to mid-level colistin resistance. Truncation of the PmrC enzyme by insertion of ISAba59 was compensated by ISAba10-mediated overproduction of EptA and, in the last isolate, the complete PmrAB two-component regulatory system was eliminated to restore the biological cost of the bacterial host. Conclusions During the in-hospital outbreak, a trajectory of genetic modification in colistin-resistant A. baumannii isolates was observed for survival in the harsh conditions imposed by life-threatening drugs with the clear purpose of maintaining drug resistance above a certain level with a reasonable fitness cost.

The StkSR Two-Component System Influences Colistin Resistance in Acinetobacter baumannii

“…Colistin is a cationic antimicrobial compound that acts by attaching and displacing the magnesium and calcium cations and thereby destabilizing the lipooligosaccharide in A. baumannii [ 69 ]. The hydrophobicity of the cell surface influences the affinity of colistin to the membrane [ 8 , 70 ].…”

The deficiency of poly-β-1,6-N-acetyl-glucosamine deacetylase trigger A. baumannii to convert to biofilm-independent colistin-tolerant cells

“…The rise of isolated clinical carbapenem-resistant MDR pathogens makes colistin a last-resort antibiotic to be considered. Currently, there are more and more heteroresistant and therapeutic failures in colistin treatment which means the colistin-resistant mechanisms that need to be identified [43][44][45] . The current studies of colistin resistance are involved in chromosomally mediated and plasmid-mediated research.…”

Comparative genomics and molecular epidemiology of colistin-resistant Acinetobacter baumannii

“…Besides 30 ColRAB from the current study, 107 previously published genomes of ColRAB isolates were downloaded from the NCBI genome database ( Table S2 ), and their STs were inferred. Therefore the inclusion criteria for 107 ColRAB genomes were the following: colistin-resistant Acinetobacter baumannii (MICs≥4 μg/mL), data obtained either from the NCBI BioSample database or from the published articles [15] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] ; NCBI quality assurance and validation of assembled genomes and inclusion in the NCBI’s RefSeq database.…”