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

Candace M. Marr, Ulrike MacDonald, Grishma Trivedi, Somnath Chakravorty, Thomas A. Russo

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8 Scopus citations


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 either meropenem or polymyxin E susceptibilities. Interestingly, biofilm formation increased resistance to polymyxin E, but had little, if any effect on meropenem activity. Additionally, BfmR mediated meropenem resistance, and perhaps polymyxin E resistance, was due to BfmR regulated factors that do not affect biofilm formation. These findings increase our understanding of the mechanisms by which BfmR mediates intrinsic antimicrobial resistance in a clinically relevant XDR isolate and suggest that the efficacy of different classes of antimicrobials may vary under biofilm inducing conditions.

Original languageEnglish (US)
Article number595798
JournalFrontiers in Microbiology
StatePublished - Oct 29 2020
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the Department of Veterans Affairs VA Merit Review (1I01BX000984 and 1I01BX004677-01A1) (Dr. Russo) and the National Institutes of Health NIH R21AI123558-01 (Dr. Russo).

Publisher Copyright:
© Copyright © 2020 Marr, MacDonald, Trivedi, Chakravorty and Russo.


  • Acinetobacter baumannii
  • BfmR
  • biofilm
  • extensively drug resistant
  • MapA
  • meropenem
  • OprB
  • polymyxin E


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