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Total Syntheses of Bulgecins A, B, and C and Their Bactericidal Potentiation of the β-Lactam Antibiotics
[Image: see text] The bulgecins are iminosaccharide secondary metabolites of the Gram-negative bacterium Paraburkholderia acidophila and inhibitors of lytic transglycosylases of bacterial cell-wall biosynthesis and remodeling. The activities of the bulgecins are intimately intertwined with the mecha...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5996343/ https://www.ncbi.nlm.nih.gov/pubmed/29716193 http://dx.doi.org/10.1021/acsinfecdis.8b00105 |
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author | Tomoshige, Shusuke Dik, David A. Akabane-Nakata, Masaaki Madukoma, Chinedu S. Fisher, Jed F. Shrout, Joshua D. Mobashery, Shahriar |
author_facet | Tomoshige, Shusuke Dik, David A. Akabane-Nakata, Masaaki Madukoma, Chinedu S. Fisher, Jed F. Shrout, Joshua D. Mobashery, Shahriar |
author_sort | Tomoshige, Shusuke |
collection | PubMed |
description | [Image: see text] The bulgecins are iminosaccharide secondary metabolites of the Gram-negative bacterium Paraburkholderia acidophila and inhibitors of lytic transglycosylases of bacterial cell-wall biosynthesis and remodeling. The activities of the bulgecins are intimately intertwined with the mechanism of a cobiosynthesized β-lactam antibiotic. β-Lactams inhibit the penicillin-binding proteins, enzymes also critical to cell-wall biosynthesis. The simultaneous loss of the lytic transglycosylase (by bulgecin) and penicillin-binding protein (by β-lactams) activities results in deformation of the septal cell wall, observed microscopically as a bulge preceding bacterial cell lysis. We describe a practical synthesis of the three naturally occurring bulgecin iminosaccharides and their mechanistic evaluation in a series of microbiological studies. These studies identify potentiation by the bulgecin at subminimum inhibitory concentrations of the β-lactam against three pathogenic Gram-negative bacteria and establish for the first time that this potentiation results in a significant increase in the bactericidal efficacy of a clinical β-lactam. |
format | Online Article Text |
id | pubmed-5996343 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-59963432018-06-13 Total Syntheses of Bulgecins A, B, and C and Their Bactericidal Potentiation of the β-Lactam Antibiotics Tomoshige, Shusuke Dik, David A. Akabane-Nakata, Masaaki Madukoma, Chinedu S. Fisher, Jed F. Shrout, Joshua D. Mobashery, Shahriar ACS Infect Dis [Image: see text] The bulgecins are iminosaccharide secondary metabolites of the Gram-negative bacterium Paraburkholderia acidophila and inhibitors of lytic transglycosylases of bacterial cell-wall biosynthesis and remodeling. The activities of the bulgecins are intimately intertwined with the mechanism of a cobiosynthesized β-lactam antibiotic. β-Lactams inhibit the penicillin-binding proteins, enzymes also critical to cell-wall biosynthesis. The simultaneous loss of the lytic transglycosylase (by bulgecin) and penicillin-binding protein (by β-lactams) activities results in deformation of the septal cell wall, observed microscopically as a bulge preceding bacterial cell lysis. We describe a practical synthesis of the three naturally occurring bulgecin iminosaccharides and their mechanistic evaluation in a series of microbiological studies. These studies identify potentiation by the bulgecin at subminimum inhibitory concentrations of the β-lactam against three pathogenic Gram-negative bacteria and establish for the first time that this potentiation results in a significant increase in the bactericidal efficacy of a clinical β-lactam. American Chemical Society 2018-05-01 2018-06-08 /pmc/articles/PMC5996343/ /pubmed/29716193 http://dx.doi.org/10.1021/acsinfecdis.8b00105 Text en Copyright © 2018 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes. |
spellingShingle | Tomoshige, Shusuke Dik, David A. Akabane-Nakata, Masaaki Madukoma, Chinedu S. Fisher, Jed F. Shrout, Joshua D. Mobashery, Shahriar Total Syntheses of Bulgecins A, B, and C and Their Bactericidal Potentiation of the β-Lactam Antibiotics |
title | Total Syntheses of Bulgecins A, B, and C and Their
Bactericidal Potentiation of the β-Lactam Antibiotics |
title_full | Total Syntheses of Bulgecins A, B, and C and Their
Bactericidal Potentiation of the β-Lactam Antibiotics |
title_fullStr | Total Syntheses of Bulgecins A, B, and C and Their
Bactericidal Potentiation of the β-Lactam Antibiotics |
title_full_unstemmed | Total Syntheses of Bulgecins A, B, and C and Their
Bactericidal Potentiation of the β-Lactam Antibiotics |
title_short | Total Syntheses of Bulgecins A, B, and C and Their
Bactericidal Potentiation of the β-Lactam Antibiotics |
title_sort | total syntheses of bulgecins a, b, and c and their
bactericidal potentiation of the β-lactam antibiotics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5996343/ https://www.ncbi.nlm.nih.gov/pubmed/29716193 http://dx.doi.org/10.1021/acsinfecdis.8b00105 |
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