Mutations in pmrB Confer Cross-Resistance between the LptD Inhibitor POL7080 and Colistin in Pseudomonas aeruginosa
Author(s)
Romano, Keith P.; Warrier, Thulasi; Poulsen, Bradley E.; Nguyen, Phuong H.; Loftis, Alexander R.; Saebi, Azin; Pentelute, Bradley L.; Hung, Deborah T; ... Show more Show less
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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.
Date issued
2019-06Department
Massachusetts Institute of Technology. Department of Chemistry; Broad Institute of MIT and HarvardPublisher
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
ISSN
0066-4804
1098-6596