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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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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. |
format | Online Article Text |
id | pubmed-9952357 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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