An Evaluation of BfmR-Regulated Antimicrobial Resistance in the Extensively Drug Resistant (XDR) Acinetobacter baumannii Strain HUMC1.

Frontiers in Microbiology
Candace M MarrThomas A Russo

Abstract

Acinetobacter baumannii is a problematic pathogen due to its common expression of extensive drug resistance (XDR) and ability to survive in the healthcare environment. These characteristics are mediated, in part, by the signal transduction system BfmR/BfmS. We previously demonstrated, in antimicrobial sensitive clinical isolates, that BfmR conferred increased resistance to meropenem and polymyxin E. In this study, potential mechanisms were informed, in part, by a prior transcriptome analysis of the antimicrobial sensitive isolate AB307-0294, which identified the porins OprB and aquaporin (Omp33-36, MapA) as plausible mediators for resistance to hydrophilic antimicrobials such as meropenem. Studies were then performed in the XDR isolate HUMC1, since delineating resistance mechanisms in this genomic background would be more translationally relevant. In HUMC1 BfmR likewise increased meropenem and polymyxin E resistance and upregulated gene expression of OprB and aquaporin. However, the comparison of HUMC1 with isogenic mutant constructs demonstrated that neither OprB nor aquaporin affected meropenem resistance; polymyxin E susceptibility was also unaffected. Next, we determined whether BfmR-mediated biofilm production affected eit...Continue Reading

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Datasets Mentioned

BETA
AB307-0294
AB307.70
CP001172.2

Methods Mentioned

BETA
PCR
Assay
RNAseq

Software Mentioned

TopHat Cufflinks
GraphPad
R
BLAST search
Prism

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