Retained colistin susceptibility in clinical Acinetobacter baumannii isolates with multiple mutations in pmrCAB and lpxACD operons
Date
2023-08
Journal Title
Journal ISSN
Volume Title
Type
Article
Publisher
Frontiers Media S.A.
Series Info
Front. Cell. Infect. Microbiol.;13:1229473
Scientific Journal Rankings
Abstract
The progressive increase in the resistance rates to first- and second-line
antibiotics has forced the reuse of colistin as last-line treatment for
Acinetobacter baumannii infections, but the emergence of colistin-resistant
strains is not uncommon. This has been long linked to acquired chromosomal
mutations in the operons pmrCAB and lpxACD. Hence, such mutations are
routinely screened in colistin-resistant strains by most studies. The current
study was designed to explore the possible existence of pmrCAB and lpxACD
mutations in colistin-susceptible isolates. For this purpose, the whole genome
sequences of eighteen multi-/extensively drug resistant A. baumannii were
generated by Illumina sequencing and screened for missense mutations of the
operons pmrCAB and lpxACD. Most of the isolates belonged to global clones
(GCs) including GC1 (n=2), GC2 (n=7), GC7 (n=2), GC9 (n=3), and GC11 (n=1).
The minimum inhibitory concentrations (MICs) of colistin were determined by
the broth microdilution assay. Seventeen isolates were fully susceptible to
colistin with MICs ranging from (≤0.125 to 0.5 µg/ml). Interestingly, all colistin-
susceptible isolates carried missense mutations in pmrCAB and lpxACD operons
with reference to A. baumannii ATCC 19606. Overall, 34 mutations were found.
Most substitutions were detected in pmrC (n=20) while no mutations were found
in pmrA or lpxA. Notably, the mutation pattern of the two operons was almost
conserved among the isolates that belonged to the same sequence type (ST) or
GC. This was also confirmed by expanding the analysis to include A. baumannii
genomes deposited in public databases. Here, we demonstrated the possible
existence of missense mutations in pmrCAB and lpxACD operons in colistin-
susceptible isolates, shedding light on the importance of interpreting mutations
with reference to colistin-susceptible isolates of the same ST/GC to avoid the
misleading impact of the ST/GC-related polymorphism. In turn, this may lead to
misinterpretation of mutations and, hence, overlooking the real players in colistin
resistance that are yet to be identified.
Description
Keywords
healthcare-associated infections, Acinetobacter baumannii, extensive drug resistance, colistin resistance, whole-genome sequencing, pmrCAB, lpxACD, mutation