Stringent Response in Mycobacteria: From Biology to Therapeutic Potential

<i>Mycobacterium tuberculosis</i> is a human pathogen that can thrive inside the host immune cells for several years and cause tuberculosis. This is due to the propensity of <i>M. tuberculosis</i> to synthesize a sturdy cell wall, shift metabolism and growth, secrete virulenc...

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Autores principales:	Kuldeepkumar Ramnaresh Gupta, Gunjan Arora, Abid Mattoo, Andaleeb Sajid
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>Mycobacterium</i> alarmones (pp)pGpp. Rel RelZ stress response drug resistance Medicine R
Acceso en línea:	https://doaj.org/article/c24af16e37ce403b9805adda7a545ecb
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spelling	oai:doaj.org-article:c24af16e37ce403b9805adda7a545ecb2021-11-25T18:38:07ZStringent Response in Mycobacteria: From Biology to Therapeutic Potential10.3390/pathogens101114172076-0817https://doaj.org/article/c24af16e37ce403b9805adda7a545ecb2021-11-01T00:00:00Zhttps://www.mdpi.com/2076-0817/10/11/1417https://doaj.org/toc/2076-0817<i>Mycobacterium tuberculosis</i> is a human pathogen that can thrive inside the host immune cells for several years and cause tuberculosis. This is due to the propensity of <i>M. tuberculosis</i> to synthesize a sturdy cell wall, shift metabolism and growth, secrete virulence factors to manipulate host immunity, and exhibit stringent response. These attributes help <i>M. tuberculosis</i> to manage the host response, and successfully establish and maintain an infection even under nutrient-deprived stress conditions for years. In this review, we will discuss the importance of mycobacterial stringent response under different stress conditions. The stringent response is mediated through small signaling molecules called alarmones “(pp)pGpp”. The synthesis and degradation of these alarmones in mycobacteria are mediated by Rel protein, which is both (p)ppGpp synthetase and hydrolase. Rel is important for all central dogma processes—DNA replication, transcription, and translation—in addition to regulating virulence, drug resistance, and biofilm formation. Rel also plays an important role in the latent infection of <i>M. tuberculosis</i>. Here, we have discussed the literature on alarmones and Rel proteins in mycobacteria and highlight that (p)ppGpp-analogs and Rel inhibitors could be designed and used as antimycobacterial compounds against <i>M. tuberculosis</i> and non-tuberculous mycobacterial infections.Kuldeepkumar Ramnaresh GuptaGunjan AroraAbid MattooAndaleeb SajidMDPI AGarticle<i>Mycobacterium</i>alarmones(pp)pGpp. RelRelZstress responsedrug resistanceMedicineRENPathogens, Vol 10, Iss 1417, p 1417 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>Mycobacterium</i> alarmones (pp)pGpp. Rel RelZ stress response drug resistance Medicine R
spellingShingle	<i>Mycobacterium</i> alarmones (pp)pGpp. Rel RelZ stress response drug resistance Medicine R Kuldeepkumar Ramnaresh Gupta Gunjan Arora Abid Mattoo Andaleeb Sajid Stringent Response in Mycobacteria: From Biology to Therapeutic Potential
description	<i>Mycobacterium tuberculosis</i> is a human pathogen that can thrive inside the host immune cells for several years and cause tuberculosis. This is due to the propensity of <i>M. tuberculosis</i> to synthesize a sturdy cell wall, shift metabolism and growth, secrete virulence factors to manipulate host immunity, and exhibit stringent response. These attributes help <i>M. tuberculosis</i> to manage the host response, and successfully establish and maintain an infection even under nutrient-deprived stress conditions for years. In this review, we will discuss the importance of mycobacterial stringent response under different stress conditions. The stringent response is mediated through small signaling molecules called alarmones “(pp)pGpp”. The synthesis and degradation of these alarmones in mycobacteria are mediated by Rel protein, which is both (p)ppGpp synthetase and hydrolase. Rel is important for all central dogma processes—DNA replication, transcription, and translation—in addition to regulating virulence, drug resistance, and biofilm formation. Rel also plays an important role in the latent infection of <i>M. tuberculosis</i>. Here, we have discussed the literature on alarmones and Rel proteins in mycobacteria and highlight that (p)ppGpp-analogs and Rel inhibitors could be designed and used as antimycobacterial compounds against <i>M. tuberculosis</i> and non-tuberculous mycobacterial infections.
format	article
author	Kuldeepkumar Ramnaresh Gupta Gunjan Arora Abid Mattoo Andaleeb Sajid
author_facet	Kuldeepkumar Ramnaresh Gupta Gunjan Arora Abid Mattoo Andaleeb Sajid
author_sort	Kuldeepkumar Ramnaresh Gupta
title	Stringent Response in Mycobacteria: From Biology to Therapeutic Potential
title_short	Stringent Response in Mycobacteria: From Biology to Therapeutic Potential
title_full	Stringent Response in Mycobacteria: From Biology to Therapeutic Potential
title_fullStr	Stringent Response in Mycobacteria: From Biology to Therapeutic Potential
title_full_unstemmed	Stringent Response in Mycobacteria: From Biology to Therapeutic Potential
title_sort	stringent response in mycobacteria: from biology to therapeutic potential
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c24af16e37ce403b9805adda7a545ecb
work_keys_str_mv	AT kuldeepkumarramnareshgupta stringentresponseinmycobacteriafrombiologytotherapeuticpotential AT gunjanarora stringentresponseinmycobacteriafrombiologytotherapeuticpotential AT abidmattoo stringentresponseinmycobacteriafrombiologytotherapeuticpotential AT andaleebsajid stringentresponseinmycobacteriafrombiologytotherapeuticpotential
_version_	1718410918493159424

Stringent Response in Mycobacteria: From Biology to Therapeutic Potential

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