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Phospholipid homeostasis, membrane tenacity and survival of Mtb in lipid rich conditions is determined by MmpL11 function

The mycobacterial cell wall is a chemically complex array of molecular entities that dictate the pathogenesis of Mycobacterium tuberculosis. Biosynthesis and maintenance of this dynamic entity in mycobacterial physiology is still poorly understood. Here we demonstrate a requirement for M. tuberculos...

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Autores principales: Bothra, Ankur, Arumugam, Prabhakar, Panchal, Vipul, Menon, Dilip, Srivastava, Sonali, Shankaran, Deepthi, Nandy, Ananya, Jaisinghani, Neetika, Singh, Archana, Gokhale, Rajesh S., Gandotra, Sheetal, Rao, Vivek
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974182/
https://www.ncbi.nlm.nih.gov/pubmed/29844505
http://dx.doi.org/10.1038/s41598-018-26710-z
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author Bothra, Ankur
Arumugam, Prabhakar
Panchal, Vipul
Menon, Dilip
Srivastava, Sonali
Shankaran, Deepthi
Nandy, Ananya
Jaisinghani, Neetika
Singh, Archana
Gokhale, Rajesh S.
Gandotra, Sheetal
Rao, Vivek
author_facet Bothra, Ankur
Arumugam, Prabhakar
Panchal, Vipul
Menon, Dilip
Srivastava, Sonali
Shankaran, Deepthi
Nandy, Ananya
Jaisinghani, Neetika
Singh, Archana
Gokhale, Rajesh S.
Gandotra, Sheetal
Rao, Vivek
author_sort Bothra, Ankur
collection PubMed
description The mycobacterial cell wall is a chemically complex array of molecular entities that dictate the pathogenesis of Mycobacterium tuberculosis. Biosynthesis and maintenance of this dynamic entity in mycobacterial physiology is still poorly understood. Here we demonstrate a requirement for M. tuberculosis MmpL11 in the maintenance of the cell wall architecture and stability in response to surface stress. In the presence of a detergent like Tyloxapol, a mmpL11 deletion mutant suffered from a severe growth attenuation as a result of altered membrane polarity, permeability and severe architectural damages. This mutant failed to tolerate permissible concentrations of cis-fatty acids suggesting its increased sensitivity to surface stress, evident as smaller colonies of the mutant outgrown from lipid rich macrophage cultures. Additionally, loss of MmpL11 led to an altered cellular fatty acid flux in the mutant: reduced incorporation into membrane cardiolipin was associated with an increased flux into the cellular triglyceride pool. This increase in storage lipids like triacyl glycerol (TAG) was associated with the altered metabolic state of higher dormancy-associated gene expression and decreased sensitivity to frontline TB drugs. This study provides a detailed mechanistic insight into the function of mmpL11 in stress adaptation of mycobacteria.
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spelling pubmed-59741822018-05-31 Phospholipid homeostasis, membrane tenacity and survival of Mtb in lipid rich conditions is determined by MmpL11 function Bothra, Ankur Arumugam, Prabhakar Panchal, Vipul Menon, Dilip Srivastava, Sonali Shankaran, Deepthi Nandy, Ananya Jaisinghani, Neetika Singh, Archana Gokhale, Rajesh S. Gandotra, Sheetal Rao, Vivek Sci Rep Article The mycobacterial cell wall is a chemically complex array of molecular entities that dictate the pathogenesis of Mycobacterium tuberculosis. Biosynthesis and maintenance of this dynamic entity in mycobacterial physiology is still poorly understood. Here we demonstrate a requirement for M. tuberculosis MmpL11 in the maintenance of the cell wall architecture and stability in response to surface stress. In the presence of a detergent like Tyloxapol, a mmpL11 deletion mutant suffered from a severe growth attenuation as a result of altered membrane polarity, permeability and severe architectural damages. This mutant failed to tolerate permissible concentrations of cis-fatty acids suggesting its increased sensitivity to surface stress, evident as smaller colonies of the mutant outgrown from lipid rich macrophage cultures. Additionally, loss of MmpL11 led to an altered cellular fatty acid flux in the mutant: reduced incorporation into membrane cardiolipin was associated with an increased flux into the cellular triglyceride pool. This increase in storage lipids like triacyl glycerol (TAG) was associated with the altered metabolic state of higher dormancy-associated gene expression and decreased sensitivity to frontline TB drugs. This study provides a detailed mechanistic insight into the function of mmpL11 in stress adaptation of mycobacteria. Nature Publishing Group UK 2018-05-29 /pmc/articles/PMC5974182/ /pubmed/29844505 http://dx.doi.org/10.1038/s41598-018-26710-z 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 Article
Bothra, Ankur
Arumugam, Prabhakar
Panchal, Vipul
Menon, Dilip
Srivastava, Sonali
Shankaran, Deepthi
Nandy, Ananya
Jaisinghani, Neetika
Singh, Archana
Gokhale, Rajesh S.
Gandotra, Sheetal
Rao, Vivek
Phospholipid homeostasis, membrane tenacity and survival of Mtb in lipid rich conditions is determined by MmpL11 function
title Phospholipid homeostasis, membrane tenacity and survival of Mtb in lipid rich conditions is determined by MmpL11 function
title_full Phospholipid homeostasis, membrane tenacity and survival of Mtb in lipid rich conditions is determined by MmpL11 function
title_fullStr Phospholipid homeostasis, membrane tenacity and survival of Mtb in lipid rich conditions is determined by MmpL11 function
title_full_unstemmed Phospholipid homeostasis, membrane tenacity and survival of Mtb in lipid rich conditions is determined by MmpL11 function
title_short Phospholipid homeostasis, membrane tenacity and survival of Mtb in lipid rich conditions is determined by MmpL11 function
title_sort phospholipid homeostasis, membrane tenacity and survival of mtb in lipid rich conditions is determined by mmpl11 function
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974182/
https://www.ncbi.nlm.nih.gov/pubmed/29844505
http://dx.doi.org/10.1038/s41598-018-26710-z
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