Mitigating the Impact of Antibacterial Drug Resistance through Host-Directed Therapies: Current Progress, Outlook, and Challenges

ABSTRACT Increasing incidences of multidrug resistance in pathogenic bacteria threaten our ability to treat and manage bacterial infection. The development and FDA approval of novel antibiotics have slowed over the past decade; therefore, the adoption and improvement of alternative therapeutic strat...

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Autores principales:	Chih-Yuan Chiang, Ijeoma Uzoma, Richard T. Moore, Merle Gilbert, Allen J. Duplantier, Rekha G. Panchal
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	antibiotic resistance fluorescent image analysis inflammation innate immunity multidrug resistance proteomics Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/7de0eec81d1e40dc8ff6383e4cf2aa95
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spelling	oai:doaj.org-article:7de0eec81d1e40dc8ff6383e4cf2aa952021-11-15T15:53:26ZMitigating the Impact of Antibacterial Drug Resistance through Host-Directed Therapies: Current Progress, Outlook, and Challenges10.1128/mBio.01932-172150-7511https://doaj.org/article/7de0eec81d1e40dc8ff6383e4cf2aa952018-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01932-17https://doaj.org/toc/2150-7511ABSTRACT Increasing incidences of multidrug resistance in pathogenic bacteria threaten our ability to treat and manage bacterial infection. The development and FDA approval of novel antibiotics have slowed over the past decade; therefore, the adoption and improvement of alternative therapeutic strategies are critical for addressing the threat posed by multidrug-resistant bacteria. Host-directed therapies utilize small-molecule drugs and proteins to alter the host response to pathogen infection. Here, we highlight strategies for modulating the host inflammatory response to enhance bacterial clearance, small-molecule potentiation of innate immunity, and targeting of host factors that are exploited by pathogen virulence factors. Application of state-of-the-art “omic” technologies, including proteomics, transcriptomics, and image-omics (image-based high-throughput phenotypic screening), combined with powerful bioinformatics tools will enable the modeling of key signaling pathways in the host-pathogen interplay and aid in the identification of host proteins for therapeutic targeting and the discovery of host-directed small molecules that will regulate bacterial infection. We conclude with an outlook on research needed to overcome the challenges associated with transitioning host-directed therapies into a clinical setting.Chih-Yuan ChiangIjeoma UzomaRichard T. MooreMerle GilbertAllen J. DuplantierRekha G. PanchalAmerican Society for Microbiologyarticleantibiotic resistancefluorescent image analysisinflammationinnate immunitymultidrug resistanceproteomicsMicrobiologyQR1-502ENmBio, Vol 9, Iss 1 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	antibiotic resistance fluorescent image analysis inflammation innate immunity multidrug resistance proteomics Microbiology QR1-502
spellingShingle	antibiotic resistance fluorescent image analysis inflammation innate immunity multidrug resistance proteomics Microbiology QR1-502 Chih-Yuan Chiang Ijeoma Uzoma Richard T. Moore Merle Gilbert Allen J. Duplantier Rekha G. Panchal Mitigating the Impact of Antibacterial Drug Resistance through Host-Directed Therapies: Current Progress, Outlook, and Challenges
description	ABSTRACT Increasing incidences of multidrug resistance in pathogenic bacteria threaten our ability to treat and manage bacterial infection. The development and FDA approval of novel antibiotics have slowed over the past decade; therefore, the adoption and improvement of alternative therapeutic strategies are critical for addressing the threat posed by multidrug-resistant bacteria. Host-directed therapies utilize small-molecule drugs and proteins to alter the host response to pathogen infection. Here, we highlight strategies for modulating the host inflammatory response to enhance bacterial clearance, small-molecule potentiation of innate immunity, and targeting of host factors that are exploited by pathogen virulence factors. Application of state-of-the-art “omic” technologies, including proteomics, transcriptomics, and image-omics (image-based high-throughput phenotypic screening), combined with powerful bioinformatics tools will enable the modeling of key signaling pathways in the host-pathogen interplay and aid in the identification of host proteins for therapeutic targeting and the discovery of host-directed small molecules that will regulate bacterial infection. We conclude with an outlook on research needed to overcome the challenges associated with transitioning host-directed therapies into a clinical setting.
format	article
author	Chih-Yuan Chiang Ijeoma Uzoma Richard T. Moore Merle Gilbert Allen J. Duplantier Rekha G. Panchal
author_facet	Chih-Yuan Chiang Ijeoma Uzoma Richard T. Moore Merle Gilbert Allen J. Duplantier Rekha G. Panchal
author_sort	Chih-Yuan Chiang
title	Mitigating the Impact of Antibacterial Drug Resistance through Host-Directed Therapies: Current Progress, Outlook, and Challenges
title_short	Mitigating the Impact of Antibacterial Drug Resistance through Host-Directed Therapies: Current Progress, Outlook, and Challenges
title_full	Mitigating the Impact of Antibacterial Drug Resistance through Host-Directed Therapies: Current Progress, Outlook, and Challenges
title_fullStr	Mitigating the Impact of Antibacterial Drug Resistance through Host-Directed Therapies: Current Progress, Outlook, and Challenges
title_full_unstemmed	Mitigating the Impact of Antibacterial Drug Resistance through Host-Directed Therapies: Current Progress, Outlook, and Challenges
title_sort	mitigating the impact of antibacterial drug resistance through host-directed therapies: current progress, outlook, and challenges
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/7de0eec81d1e40dc8ff6383e4cf2aa95
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Mitigating the Impact of Antibacterial Drug Resistance through Host-Directed Therapies: Current Progress, Outlook, and Challenges

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