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Precision antimicrobial therapeutics: the path of least resistance?

The emergence of drug-resistant pathogens has led to a decline in the efficacy of traditional antimicrobial therapy. The rise in resistance has been driven by widespread use, and in some cases misuse, of antibacterial agents in treating a variety of infections. A growing body of research has begun t...

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Autores principales: Spaulding, Caitlin N., Klein, Roger D., Schreiber, Henry L., Janetka, James W., Hultgren, Scott J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5829159/
https://www.ncbi.nlm.nih.gov/pubmed/29507749
http://dx.doi.org/10.1038/s41522-018-0048-3
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author Spaulding, Caitlin N.
Klein, Roger D.
Schreiber, Henry L.
Janetka, James W.
Hultgren, Scott J.
author_facet Spaulding, Caitlin N.
Klein, Roger D.
Schreiber, Henry L.
Janetka, James W.
Hultgren, Scott J.
author_sort Spaulding, Caitlin N.
collection PubMed
description The emergence of drug-resistant pathogens has led to a decline in the efficacy of traditional antimicrobial therapy. The rise in resistance has been driven by widespread use, and in some cases misuse, of antibacterial agents in treating a variety of infections. A growing body of research has begun to elucidate the harmful effects of broad-spectrum antibiotic therapy on the beneficial host microbiota. To combat these threats, increasing effort is being directed toward the development of precision antimicrobial therapeutics that target key virulence determinants of specific pathogens while leaving the remainder of the host microbiota undisturbed. This includes the recent development of small molecules termed “mannosides” that specifically target uropathogenic E. coli (UPEC). Mannosides are glycomimetics of the natural mannosylated host receptor for type 1 pili, extracellular appendages that promotes UPEC colonization in the intestine. Type 1 pili are also critical for colonization and infection in the bladder. In both cases, mannosides act as molecular decoys which potently prevent bacteria from binding to host tissues. In mice, oral treatment with mannosides simultaneously clears active bladder infection and removes intestinal UPEC while leaving the gut microbiota structure relatively unchanged. Similar treatment strategies successfully target other pathogens, like adherent-invasive E. coli (AIEC), an organism associated with Crohn’s disease (CD), in mouse models. While not without its challenges, antibiotic-sparing therapeutic approaches hold great promise in a variety of disease systems, including UTI, CD, otitis media (OM), and others. In this perspective we highlight the benefits, progress, and roadblocks to the development of precision antimicrobial therapeutics.
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spelling pubmed-58291592018-03-05 Precision antimicrobial therapeutics: the path of least resistance? Spaulding, Caitlin N. Klein, Roger D. Schreiber, Henry L. Janetka, James W. Hultgren, Scott J. NPJ Biofilms Microbiomes Perspective The emergence of drug-resistant pathogens has led to a decline in the efficacy of traditional antimicrobial therapy. The rise in resistance has been driven by widespread use, and in some cases misuse, of antibacterial agents in treating a variety of infections. A growing body of research has begun to elucidate the harmful effects of broad-spectrum antibiotic therapy on the beneficial host microbiota. To combat these threats, increasing effort is being directed toward the development of precision antimicrobial therapeutics that target key virulence determinants of specific pathogens while leaving the remainder of the host microbiota undisturbed. This includes the recent development of small molecules termed “mannosides” that specifically target uropathogenic E. coli (UPEC). Mannosides are glycomimetics of the natural mannosylated host receptor for type 1 pili, extracellular appendages that promotes UPEC colonization in the intestine. Type 1 pili are also critical for colonization and infection in the bladder. In both cases, mannosides act as molecular decoys which potently prevent bacteria from binding to host tissues. In mice, oral treatment with mannosides simultaneously clears active bladder infection and removes intestinal UPEC while leaving the gut microbiota structure relatively unchanged. Similar treatment strategies successfully target other pathogens, like adherent-invasive E. coli (AIEC), an organism associated with Crohn’s disease (CD), in mouse models. While not without its challenges, antibiotic-sparing therapeutic approaches hold great promise in a variety of disease systems, including UTI, CD, otitis media (OM), and others. In this perspective we highlight the benefits, progress, and roadblocks to the development of precision antimicrobial therapeutics. Nature Publishing Group UK 2018-02-27 /pmc/articles/PMC5829159/ /pubmed/29507749 http://dx.doi.org/10.1038/s41522-018-0048-3 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Perspective
Spaulding, Caitlin N.
Klein, Roger D.
Schreiber, Henry L.
Janetka, James W.
Hultgren, Scott J.
Precision antimicrobial therapeutics: the path of least resistance?
title Precision antimicrobial therapeutics: the path of least resistance?
title_full Precision antimicrobial therapeutics: the path of least resistance?
title_fullStr Precision antimicrobial therapeutics: the path of least resistance?
title_full_unstemmed Precision antimicrobial therapeutics: the path of least resistance?
title_short Precision antimicrobial therapeutics: the path of least resistance?
title_sort precision antimicrobial therapeutics: the path of least resistance?
topic Perspective
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5829159/
https://www.ncbi.nlm.nih.gov/pubmed/29507749
http://dx.doi.org/10.1038/s41522-018-0048-3
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