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Penetration through Outer Membrane and Efflux Potential in Pseudomonas aeruginosa of Bulgecin A as an Adjuvant to β-Lactam Antibiotics

The treatment of infections by Gram-negative bacteria remains a difficult clinical challenge. In the light of the dearth of discovery of novel antibiotics, one strategy that is being explored is the use of adjuvants to enhance antibacterial activities of existing antibiotics. One such adjuvant is bu...

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Autores principales: Kim, Choon, Tomoshige, Shusuke, Lee, Mijoon, Zgurskaya, Helen I., Mobashery, Shahriar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9952357/
https://www.ncbi.nlm.nih.gov/pubmed/36830269
http://dx.doi.org/10.3390/antibiotics12020358
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author Kim, Choon
Tomoshige, Shusuke
Lee, Mijoon
Zgurskaya, Helen I.
Mobashery, Shahriar
author_facet Kim, Choon
Tomoshige, Shusuke
Lee, Mijoon
Zgurskaya, Helen I.
Mobashery, Shahriar
author_sort Kim, Choon
collection PubMed
description The treatment of infections by Gram-negative bacteria remains a difficult clinical challenge. In the light of the dearth of discovery of novel antibiotics, one strategy that is being explored is the use of adjuvants to enhance antibacterial activities of existing antibiotics. One such adjuvant is bulgecin A, which allows for the lowering of minimal-inhibitory concentrations for β-lactam antibiotics. We have shown that bulgecin A inhibits three of the pseudomonal lytic transglycosylases in its mode of action, yet high concentrations are needed for potentiation activity. Herein, we document that bulgecin A is not a substrate for pseudomonal efflux pumps, whose functions could have been a culprit in the need for high concentrations. We present evidence that the penetration barrier into the periplasm is at the root of the need for high concentrations of bulgecin A in its potentiation of β-lactam antibiotics.
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spelling pubmed-99523572023-02-25 Penetration through Outer Membrane and Efflux Potential in Pseudomonas aeruginosa of Bulgecin A as an Adjuvant to β-Lactam Antibiotics Kim, Choon Tomoshige, Shusuke Lee, Mijoon Zgurskaya, Helen I. Mobashery, Shahriar Antibiotics (Basel) Brief Report The treatment of infections by Gram-negative bacteria remains a difficult clinical challenge. In the light of the dearth of discovery of novel antibiotics, one strategy that is being explored is the use of adjuvants to enhance antibacterial activities of existing antibiotics. One such adjuvant is bulgecin A, which allows for the lowering of minimal-inhibitory concentrations for β-lactam antibiotics. We have shown that bulgecin A inhibits three of the pseudomonal lytic transglycosylases in its mode of action, yet high concentrations are needed for potentiation activity. Herein, we document that bulgecin A is not a substrate for pseudomonal efflux pumps, whose functions could have been a culprit in the need for high concentrations. We present evidence that the penetration barrier into the periplasm is at the root of the need for high concentrations of bulgecin A in its potentiation of β-lactam antibiotics. MDPI 2023-02-09 /pmc/articles/PMC9952357/ /pubmed/36830269 http://dx.doi.org/10.3390/antibiotics12020358 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Report
Kim, Choon
Tomoshige, Shusuke
Lee, Mijoon
Zgurskaya, Helen I.
Mobashery, Shahriar
Penetration through Outer Membrane and Efflux Potential in Pseudomonas aeruginosa of Bulgecin A as an Adjuvant to β-Lactam Antibiotics
title Penetration through Outer Membrane and Efflux Potential in Pseudomonas aeruginosa of Bulgecin A as an Adjuvant to β-Lactam Antibiotics
title_full Penetration through Outer Membrane and Efflux Potential in Pseudomonas aeruginosa of Bulgecin A as an Adjuvant to β-Lactam Antibiotics
title_fullStr Penetration through Outer Membrane and Efflux Potential in Pseudomonas aeruginosa of Bulgecin A as an Adjuvant to β-Lactam Antibiotics
title_full_unstemmed Penetration through Outer Membrane and Efflux Potential in Pseudomonas aeruginosa of Bulgecin A as an Adjuvant to β-Lactam Antibiotics
title_short Penetration through Outer Membrane and Efflux Potential in Pseudomonas aeruginosa of Bulgecin A as an Adjuvant to β-Lactam Antibiotics
title_sort penetration through outer membrane and efflux potential in pseudomonas aeruginosa of bulgecin a as an adjuvant to β-lactam antibiotics
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9952357/
https://www.ncbi.nlm.nih.gov/pubmed/36830269
http://dx.doi.org/10.3390/antibiotics12020358
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