The WblC/WhiB7 Transcription Factor Controls Intrinsic Resistance to Translation-Targeting Antibiotics by Altering Ribosome Composition

ABSTRACT Bacteria that encounter antibiotics can efficiently change their physiology to develop resistance. This intrinsic antibiotic resistance is mediated by multiple pathways, including a regulatory system(s) that activates specific genes. In some Streptomyces and Mycobacterium spp., the WblC/Whi...

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Autores principales:	Ju-Hyung Lee, Ji-Sun Yoo, Yeonbum Kim, Jong-Seo Kim, Eun-Jin Lee, Jung-Hye Roe
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Streptomyces coelicolor WhiB-like protein antibiotic resistance ribosome-associated proteins translation-targeting antibiotics Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/02bd04aa48ea437cb52098bf5d62878c
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spelling	oai:doaj.org-article:02bd04aa48ea437cb52098bf5d62878c2021-11-15T15:57:02ZThe WblC/WhiB7 Transcription Factor Controls Intrinsic Resistance to Translation-Targeting Antibiotics by Altering Ribosome Composition10.1128/mBio.00625-202150-7511https://doaj.org/article/02bd04aa48ea437cb52098bf5d62878c2020-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00625-20https://doaj.org/toc/2150-7511ABSTRACT Bacteria that encounter antibiotics can efficiently change their physiology to develop resistance. This intrinsic antibiotic resistance is mediated by multiple pathways, including a regulatory system(s) that activates specific genes. In some Streptomyces and Mycobacterium spp., the WblC/WhiB7 transcription factor is required for intrinsic resistance to translation-targeting antibiotics. Wide conservation of WblC/WhiB7 within Actinobacteria indicates a critical role of WblC/WhiB7 in developing resistance to such antibiotics. Here, we identified 312 WblC target genes in Streptomyces coelicolor, a model antibiotic-producing bacterium, using a combined analysis of RNA sequencing and chromatin immunoprecipitation sequencing. Interestingly, WblC controls many genes involved in translation, in addition to previously identified antibiotic resistance genes. Moreover, WblC promotes translation rate during antibiotic stress by altering the ribosome-associated protein composition. Our genome-wide analyses highlight a previously unappreciated antibiotic resistance mechanism that modifies ribosome composition and maintains the translation rate in the presence of sub-MIC levels of antibiotics. IMPORTANCE The emergence of antibiotic-resistant bacteria is one of the top threats in human health. Therefore, we need to understand how bacteria acquire resistance to antibiotics and continue growth even in the presence of antibiotics. Streptomyces coelicolor, an antibiotic-producing soil bacterium, intrinsically develops resistance to translation-targeting antibiotics. Intrinsic resistance is controlled by the WblC/WhiB7 transcription factor that is highly conserved within Actinobacteria, including Mycobacterium tuberculosis. Here, identification of the WblC/WhiB7 regulon revealed that WblC/WhiB7 controls ribosome maintenance genes and promotes translation in the presence of antibiotics by altering the composition of ribosome-associated proteins. Also, the WblC-mediated ribosomal alteration is indeed required for resistance to translation-targeting antibiotics. This suggests that inactivation of the WblC/WhiB7 regulon could be a potential target to treat antibiotic-resistant mycobacteria.Ju-Hyung LeeJi-Sun YooYeonbum KimJong-Seo KimEun-Jin LeeJung-Hye RoeAmerican Society for MicrobiologyarticleStreptomyces coelicolorWhiB-like proteinantibiotic resistanceribosome-associated proteinstranslation-targeting antibioticsMicrobiologyQR1-502ENmBio, Vol 11, Iss 2 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Streptomyces coelicolor WhiB-like protein antibiotic resistance ribosome-associated proteins translation-targeting antibiotics Microbiology QR1-502
spellingShingle	Streptomyces coelicolor WhiB-like protein antibiotic resistance ribosome-associated proteins translation-targeting antibiotics Microbiology QR1-502 Ju-Hyung Lee Ji-Sun Yoo Yeonbum Kim Jong-Seo Kim Eun-Jin Lee Jung-Hye Roe The WblC/WhiB7 Transcription Factor Controls Intrinsic Resistance to Translation-Targeting Antibiotics by Altering Ribosome Composition
description	ABSTRACT Bacteria that encounter antibiotics can efficiently change their physiology to develop resistance. This intrinsic antibiotic resistance is mediated by multiple pathways, including a regulatory system(s) that activates specific genes. In some Streptomyces and Mycobacterium spp., the WblC/WhiB7 transcription factor is required for intrinsic resistance to translation-targeting antibiotics. Wide conservation of WblC/WhiB7 within Actinobacteria indicates a critical role of WblC/WhiB7 in developing resistance to such antibiotics. Here, we identified 312 WblC target genes in Streptomyces coelicolor, a model antibiotic-producing bacterium, using a combined analysis of RNA sequencing and chromatin immunoprecipitation sequencing. Interestingly, WblC controls many genes involved in translation, in addition to previously identified antibiotic resistance genes. Moreover, WblC promotes translation rate during antibiotic stress by altering the ribosome-associated protein composition. Our genome-wide analyses highlight a previously unappreciated antibiotic resistance mechanism that modifies ribosome composition and maintains the translation rate in the presence of sub-MIC levels of antibiotics. IMPORTANCE The emergence of antibiotic-resistant bacteria is one of the top threats in human health. Therefore, we need to understand how bacteria acquire resistance to antibiotics and continue growth even in the presence of antibiotics. Streptomyces coelicolor, an antibiotic-producing soil bacterium, intrinsically develops resistance to translation-targeting antibiotics. Intrinsic resistance is controlled by the WblC/WhiB7 transcription factor that is highly conserved within Actinobacteria, including Mycobacterium tuberculosis. Here, identification of the WblC/WhiB7 regulon revealed that WblC/WhiB7 controls ribosome maintenance genes and promotes translation in the presence of antibiotics by altering the composition of ribosome-associated proteins. Also, the WblC-mediated ribosomal alteration is indeed required for resistance to translation-targeting antibiotics. This suggests that inactivation of the WblC/WhiB7 regulon could be a potential target to treat antibiotic-resistant mycobacteria.
format	article
author	Ju-Hyung Lee Ji-Sun Yoo Yeonbum Kim Jong-Seo Kim Eun-Jin Lee Jung-Hye Roe
author_facet	Ju-Hyung Lee Ji-Sun Yoo Yeonbum Kim Jong-Seo Kim Eun-Jin Lee Jung-Hye Roe
author_sort	Ju-Hyung Lee
title	The WblC/WhiB7 Transcription Factor Controls Intrinsic Resistance to Translation-Targeting Antibiotics by Altering Ribosome Composition
title_short	The WblC/WhiB7 Transcription Factor Controls Intrinsic Resistance to Translation-Targeting Antibiotics by Altering Ribosome Composition
title_full	The WblC/WhiB7 Transcription Factor Controls Intrinsic Resistance to Translation-Targeting Antibiotics by Altering Ribosome Composition
title_fullStr	The WblC/WhiB7 Transcription Factor Controls Intrinsic Resistance to Translation-Targeting Antibiotics by Altering Ribosome Composition
title_full_unstemmed	The WblC/WhiB7 Transcription Factor Controls Intrinsic Resistance to Translation-Targeting Antibiotics by Altering Ribosome Composition
title_sort	wblc/whib7 transcription factor controls intrinsic resistance to translation-targeting antibiotics by altering ribosome composition
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/02bd04aa48ea437cb52098bf5d62878c
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The WblC/WhiB7 Transcription Factor Controls Intrinsic Resistance to Translation-Targeting Antibiotics by Altering Ribosome Composition

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