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

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 p...

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Autores principales: Romano, Keith P., Warrier, Thulasi, Poulsen, Bradley E., Nguyen, Phuong H., Loftis, Alexander R., Saebi, Azin, Pentelute, Bradley L., Hung, Deborah T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2019
Materias:
Mechanisms of Resistance
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6709506/
https://www.ncbi.nlm.nih.gov/pubmed/31235628
http://dx.doi.org/10.1128/AAC.00511-19
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author Romano, Keith P.
Warrier, Thulasi
Poulsen, Bradley E.
Nguyen, Phuong H.
Loftis, Alexander R.
Saebi, Azin
Pentelute, Bradley L.
Hung, Deborah T.
author_facet Romano, Keith P.
Warrier, Thulasi
Poulsen, Bradley E.
Nguyen, Phuong H.
Loftis, Alexander R.
Saebi, Azin
Pentelute, Bradley L.
Hung, Deborah T.
author_sort Romano, Keith P.
collection PubMed
description 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.
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spelling pubmed-67095062019-09-11 Mutations in pmrB Confer Cross-Resistance between the LptD Inhibitor POL7080 and Colistin in Pseudomonas aeruginosa Romano, Keith P. Warrier, Thulasi Poulsen, Bradley E. Nguyen, Phuong H. Loftis, Alexander R. Saebi, Azin Pentelute, Bradley L. Hung, Deborah T. Antimicrob Agents Chemother Mechanisms of Resistance 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. American Society for Microbiology 2019-08-23 /pmc/articles/PMC6709506/ /pubmed/31235628 http://dx.doi.org/10.1128/AAC.00511-19 Text en Copyright © 2019 Romano et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Mechanisms of Resistance
Romano, Keith P.
Warrier, Thulasi
Poulsen, Bradley E.
Nguyen, Phuong H.
Loftis, Alexander R.
Saebi, Azin
Pentelute, Bradley L.
Hung, Deborah T.
Mutations in pmrB Confer Cross-Resistance between the LptD Inhibitor POL7080 and Colistin in Pseudomonas aeruginosa
title Mutations in pmrB Confer Cross-Resistance between the LptD Inhibitor POL7080 and Colistin in Pseudomonas aeruginosa
title_full Mutations in pmrB Confer Cross-Resistance between the LptD Inhibitor POL7080 and Colistin in Pseudomonas aeruginosa
title_fullStr Mutations in pmrB Confer Cross-Resistance between the LptD Inhibitor POL7080 and Colistin in Pseudomonas aeruginosa
title_full_unstemmed Mutations in pmrB Confer Cross-Resistance between the LptD Inhibitor POL7080 and Colistin in Pseudomonas aeruginosa
title_short Mutations in pmrB Confer Cross-Resistance between the LptD Inhibitor POL7080 and Colistin in Pseudomonas aeruginosa
title_sort mutations in pmrb confer cross-resistance between the lptd inhibitor pol7080 and colistin in pseudomonas aeruginosa
topic Mechanisms of Resistance
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6709506/
https://www.ncbi.nlm.nih.gov/pubmed/31235628
http://dx.doi.org/10.1128/AAC.00511-19
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