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Mutations in pmrB Confer Cross-Resistance between the LptD Inhibitor POL7080 and Colistin in Pseudomonas aeruginosa.

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.

SUBMITTER: Romano KP

PROVIDER: S-EPMC6709506 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Mutations in pmrB Confer Cross-Resistance between the LptD Inhibitor POL7080 and Colistin in Pseudomonas aeruginosa.

Romano Keith P KP Warrier Thulasi T Poulsen Bradley E BE Nguyen Phuong H PH Loftis Alexander R AR Saebi Azin A Pentelute Bradley L BL Hung Deborah T DT

Antimicrobial agents and chemotherapy 20190823 9

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 resist ...[more]

PMID: 31235628

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