Novel Populations of <i>Mycobacterium smegmatis</i> Under Hypoxia and Starvation: Some Insights on Cell Viability and Morphological Changes

The general features of the shift to a dormant state in mycobacterial species include several phenotypic changes, reduced metabolic activities, and increased resistance to host and environmental stress conditions. In this study, we aimed to provide novel insights into the viability state and morphol...

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Main Authors: Ruben Zaragoza-Contreras, Diana A. Aguilar-Ayala, Lázaro García-Morales, Miguel A. Ares, Addy Cecilia Helguera-Repetto, Jorge Francisco Cerna-Cortés, Lizbel León-Solis, Fernando Suárez-Sánchez, Jorge A. González-Y-Merchand, Sandra Rivera-Gutiérrez
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Microorganisms
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Online Access:https://www.mdpi.com/2076-2607/12/11/2280
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author Ruben Zaragoza-Contreras
Diana A. Aguilar-Ayala
Lázaro García-Morales
Miguel A. Ares
Addy Cecilia Helguera-Repetto
Jorge Francisco Cerna-Cortés
Lizbel León-Solis
Fernando Suárez-Sánchez
Jorge A. González-Y-Merchand
Sandra Rivera-Gutiérrez
author_facet Ruben Zaragoza-Contreras
Diana A. Aguilar-Ayala
Lázaro García-Morales
Miguel A. Ares
Addy Cecilia Helguera-Repetto
Jorge Francisco Cerna-Cortés
Lizbel León-Solis
Fernando Suárez-Sánchez
Jorge A. González-Y-Merchand
Sandra Rivera-Gutiérrez
author_sort Ruben Zaragoza-Contreras
collection DOAJ
description The general features of the shift to a dormant state in mycobacterial species include several phenotypic changes, reduced metabolic activities, and increased resistance to host and environmental stress conditions. In this study, we aimed to provide novel insights into the viability state and morphological changes in dormant <i>M. smegmatis</i> that contribute to its long-term survival under starvation or hypoxia. To this end, we conducted assays to evaluate cell viability, morphological changes and gene expression. During starvation, <i>M. smegmatis</i> exhibited a reduction in cell length, the presence of viable but non-culturable (VBNC) cells and the formation of anucleated small cells, potentially due to a phenomenon known as reductive cell division. Under hypoxia, a novel population of pleomorphic mycobacteria with a rough surface before the cells reached nonreplicating persistence 1 (NRP1) was identified. This population exhibited VBNC-like behaviour, with a loss of cell wall rigidity and the presence of lipid-body-like structures. Based on <i>dosR</i> and <i>hspX</i> expression, we suggest that <i>M. smegmatis</i> encounters reductive stress conditions during starvation, while lipid storage may induce oxidative stress during hypoxia. These insights into the heterogeneous populations presented here could offer valuable opportunities for developing new therapeutic strategies to control dormant mycobacterial populations.
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spelling doaj-art-8a459fe5cc0a42d893c695ab2e4668252025-08-20T02:48:01ZengMDPI AGMicroorganisms2076-26072024-11-011211228010.3390/microorganisms12112280Novel Populations of <i>Mycobacterium smegmatis</i> Under Hypoxia and Starvation: Some Insights on Cell Viability and Morphological ChangesRuben Zaragoza-Contreras0Diana A. Aguilar-Ayala1Lázaro García-Morales2Miguel A. Ares3Addy Cecilia Helguera-Repetto4Jorge Francisco Cerna-Cortés5Lizbel León-Solis6Fernando Suárez-Sánchez7Jorge A. González-Y-Merchand8Sandra Rivera-Gutiérrez9Departamento de Microbiología Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional (ENCB, IPN), Ciudad de México 11340, MexicoDepartamento de Microbiología Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional (ENCB, IPN), Ciudad de México 11340, MexicoDepartamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Ciudad de México 07360, MexicoDepartamento de Microbiología Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional (ENCB, IPN), Ciudad de México 11340, MexicoDepartamento de Inmunobioquímica, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes (InPer), Ciudad de México 11000, MexicoDepartamento de Microbiología Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional (ENCB, IPN), Ciudad de México 11340, MexicoDepartamento de Microbiología Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional (ENCB, IPN), Ciudad de México 11340, MexicoUnidad de Investigación Médica en Bioquímica, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Hospital de Especialidades, Mexico City 06720, MexicoDepartamento de Microbiología Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional (ENCB, IPN), Ciudad de México 11340, MexicoDepartamento de Microbiología Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional (ENCB, IPN), Ciudad de México 11340, MexicoThe general features of the shift to a dormant state in mycobacterial species include several phenotypic changes, reduced metabolic activities, and increased resistance to host and environmental stress conditions. In this study, we aimed to provide novel insights into the viability state and morphological changes in dormant <i>M. smegmatis</i> that contribute to its long-term survival under starvation or hypoxia. To this end, we conducted assays to evaluate cell viability, morphological changes and gene expression. During starvation, <i>M. smegmatis</i> exhibited a reduction in cell length, the presence of viable but non-culturable (VBNC) cells and the formation of anucleated small cells, potentially due to a phenomenon known as reductive cell division. Under hypoxia, a novel population of pleomorphic mycobacteria with a rough surface before the cells reached nonreplicating persistence 1 (NRP1) was identified. This population exhibited VBNC-like behaviour, with a loss of cell wall rigidity and the presence of lipid-body-like structures. Based on <i>dosR</i> and <i>hspX</i> expression, we suggest that <i>M. smegmatis</i> encounters reductive stress conditions during starvation, while lipid storage may induce oxidative stress during hypoxia. These insights into the heterogeneous populations presented here could offer valuable opportunities for developing new therapeutic strategies to control dormant mycobacterial populations.https://www.mdpi.com/2076-2607/12/11/2280<i>Mycobacterium smegmatis</i>dormancystarvationhypoxiagene expression
spellingShingle Ruben Zaragoza-Contreras
Diana A. Aguilar-Ayala
Lázaro García-Morales
Miguel A. Ares
Addy Cecilia Helguera-Repetto
Jorge Francisco Cerna-Cortés
Lizbel León-Solis
Fernando Suárez-Sánchez
Jorge A. González-Y-Merchand
Sandra Rivera-Gutiérrez
Novel Populations of <i>Mycobacterium smegmatis</i> Under Hypoxia and Starvation: Some Insights on Cell Viability and Morphological Changes
Microorganisms
<i>Mycobacterium smegmatis</i>
dormancy
starvation
hypoxia
gene expression
title Novel Populations of <i>Mycobacterium smegmatis</i> Under Hypoxia and Starvation: Some Insights on Cell Viability and Morphological Changes
title_full Novel Populations of <i>Mycobacterium smegmatis</i> Under Hypoxia and Starvation: Some Insights on Cell Viability and Morphological Changes
title_fullStr Novel Populations of <i>Mycobacterium smegmatis</i> Under Hypoxia and Starvation: Some Insights on Cell Viability and Morphological Changes
title_full_unstemmed Novel Populations of <i>Mycobacterium smegmatis</i> Under Hypoxia and Starvation: Some Insights on Cell Viability and Morphological Changes
title_short Novel Populations of <i>Mycobacterium smegmatis</i> Under Hypoxia and Starvation: Some Insights on Cell Viability and Morphological Changes
title_sort novel populations of i mycobacterium smegmatis i under hypoxia and starvation some insights on cell viability and morphological changes
topic <i>Mycobacterium smegmatis</i>
dormancy
starvation
hypoxia
gene expression
url https://www.mdpi.com/2076-2607/12/11/2280
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