Journal article

Cell Membrane Adaptations Mediate beta-Lactam-Induced Resensitization of Daptomycin-Resistant (DAP-R) Staphylococcus aureus In Vitro

Nagendra N Mishra, Arnold S Bayer, Sarah L Baines, Ashleigh S Hayes, Benjamin P Howden, Christian K Lapitan, Cassandra Lew, Warren E Rose

MICROORGANISMS | MDPI | Published : 2021

Abstract

The reversal of daptomycin resistance in MRSA to a daptomycin-susceptible phenotype following prolonged passage in selected β-lactams occurs coincident with the accumulation of multiple point mutations in the mprF gene. MprF regulates surface charge by modulating the content and translocation of the positively charged cell membrane phospholipid, lysyl-phosphatidylglycerol (LPG). The precise cell membrane adaptations accompanying such β-lactam-induced mprF perturbations are unknown. This study examined key cell membrane metrics relevant to antimicrobial resistance among three daptomycin-resistant MRSA clinical strains, which became daptomycin-susceptible following prolonged exposure to cloxac..

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Grants

Awarded by NIH/NIAID


Awarded by Lundquist Institute at Harbor UCLA


Funding Acknowledgements

This research was supported by grants from NIH/NIAID: R01 AI132627 (to WER) and R01AI130056 (to ASB). NNM was supported by Lundquist Institute at Harbor UCLA intramural research grant (#531604-01-01).