ISAba1-dependent overexpression of eptA in clinical strains of Acinetobacter baumannii resistant to colistin

Abstract

Background Colistin resistance in Acinetobacter baumannii often results from mutational activation of the two-component system PmrAB and subsequent addition of phospho-ethanolamine (pEtN) to lipooligosaccharide by up-regulated pEtN transferase PmrC. Objectives To characterize mechanisms of colistin resistance independent of PmrCAB in A. baumannii. Methods Twenty-seven colistin-resistant A. baumannii were collected from 2012 to 2018. Analysis of operon pmrCAB was performed by PCR and sequencing. Seven strains were investigated further by WGS and whole-genome MLST (wgMLST). Results Seven out of the 27 selected isolates were found to overexpress eptA, a gene homologous to pmrC, likely as a consequence of upstream insertion of an ISAba1 element. Insertion sites of ISAba1 were mapped 13, 18 and 156 bp ahead of the start codon of eptA in five strains, one strain and one strain, respectively. The finding that the isolates did not cluster together when compared by wgMLST analysis supports the notion that distinct insertion events occurred in close, but different, genetic backgrounds. Conclusions Activation of eptA and subsequent addition of pEtN to the cell surface represents a novel mechanism of resistance to colistin in A. baumannii.

Colistin resistance inAcinetobacter baumanniiis driven by multiple genomic traits: Evaluating the role of ISAba1-driveneptAoverexpression among Indian isolates

“…eptA is a pmrC homologue with pEtN transferase activity [8]. In this study, eptA was present in both CR-ColSAB and CR-ColRAB and comparable with previous studies [3, 7 -8, 35].…”

“…baumannii [32]. Earlier studies reported IC2/global clone 2 (GC2) as the predominant lineage associated with outbreaks [8]. This finding correlates with the current study and identified in both CR-ColRAB and CR-ColSAB In the present study, IC1/GC1was identified among CR-ColSAB which is contrast to Snyman et al where GC1 was identified in both CR-ColSAB and CR-ColRAB [33].…”

“…In A. baumannii colistin resistance is mediated by multiple mechanisms [8]. This includes, (i) Loss of lipopolysaccharide (LPS) production, due to mutations in lipid A biosynthesis genes like lpxA, lpxC and lpxD.…”

Abundance of Colistin-Resistant, OXA-23- and ArmA-Producing Acinetobacter baumannii Belonging to International Clone 2 in Greece

“…Colistin resistance may also result from the overexpression of etpA, a pmrC homolog. This is mediated by insertional inactivation of a gene encoding an H-NS family transcriptional regulator (Lucas et al, 2018) or by integration of insertion sequence elements upstream of the eptA gene itself (Gerson et al, 2019;Potron et al, 2019;Trebosc et al, 2019).…”

Sequence Duplication Within pmrB Gene Contribute to High-Level Colistin Resistance in Avian Pathogenic Escherichia coli

“…pmrA, phoPQ, mgrB, and lpxACD reported in other Gramnegative bacteria were not found in this study. 23,46,51,52 The above results indicate that PmrB-sd mutations contributed to, but were not fully responsible for, HLCR in APEC strains. Two possible mechanisms might be contributed to HLCR in E. coli: (1) pmrB mutation coupled with mutation in genes involved in LPS modification and hyperproduction of capsular polysaccharide, or encoding porins and efflux pumps 23,[53][54][55] ;…”