Mutations in pmrB Confer Cross-Resistance between the LptD Inhibitor POL7080 and Colistin in Pseudomonas aeruginosa
Name
Antimicrobial Agents and Chemotherapy-2019-Romano-e00511-19.full.pdf
Description
Published version
Size
1.35 MB
Format
Adobe PDF
Checksum (MD5)
2835d3978d24b9e8ab1857a813936ff4
Author(s)
Romano, Keith P.
Warrier, Thulasi
Poulsen, Bradley E.
Nguyen, Phuong H.
Loftis, Alexander R.
Saebi, Azin
Pentelute, Bradley L.
Hung, Deborah T
Date Issued
June 2019
Publisher
American Society for Microbiology
Citation
Romano, Keith P. "Mutations in pmrB Confer Cross-Resistance between the LptD Inhibitor POL7080 and Colistin in Pseudomonas aeruginosa." Mechanisms of Resistance 63, 9 (August 2019): e00511-19 © 2019 The Authors
Version
Final published version
Abstract
Pseudomonas aeruginosa is a major bacterial pathogen associated with a rising prevalence of antibiotic resistance. We evaluated the resistance mechanisms of P. aeruginosa against POL7080, a species-specific, first-in-class antibiotic in clinical trials that targets the lipopolysaccharide transport protein LptD. We isolated a series of POL7080-resistant strains with mutations in the two-component sensor gene pmrB. Transcriptomic and confocal microscopy studies support a resistance mechanism shared with colistin, involving lipopolysaccharide modifications that mitigate antibiotic cell surface binding.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Broad Institute of MIT and Harvard
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1128/aac.00511-19
