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Advance in Research on Mycobacterium tuberculosis FabG4 and Its Inhibitor

Increasing evidence from recent reports of drug-resistant mycobacterial strains poses a challenge worldwide. Drug-resistant strains often undergo mutations, adopt alternative pathways, and express drug efflux pumps to reduce or eliminate drug doses. Besides these intrinsic resistance mechanisms, bac...

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Autor principal: Dutta, Debajyoti
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6008564/
https://www.ncbi.nlm.nih.gov/pubmed/29946302
http://dx.doi.org/10.3389/fmicb.2018.01184
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author Dutta, Debajyoti
author_facet Dutta, Debajyoti
author_sort Dutta, Debajyoti
collection PubMed
description Increasing evidence from recent reports of drug-resistant mycobacterial strains poses a challenge worldwide. Drug-resistant strains often undergo mutations, adopt alternative pathways, and express drug efflux pumps to reduce or eliminate drug doses. Besides these intrinsic resistance mechanisms, bacteria can evade drug doses by forming biofilms. Biofilms are the concerted growth of adherent microorganisms, which can also be formed at the air-water interface. The growth is supported by the extracellular polymer matrix which is self-produced by the microorganisms. Reduced metabolic activity in a nutrient-deficient environment in the biofilm may cause the microorganisms to take alternative pathways that can make the microorganisms recalcitrant to the drug doses. Recent works have shown that Mycobacterium tuberculosis expresses several proteins during its growth in biofilm, those when deleted, did not show any effect on mycobacterial growth in normal nutrient-sufficient conditions. Studying these unconventional proteins in mycobacterial biofilms is therefore of utmost importance. In this article, I will discuss one such mycobacterial biofilm-related protein FabG4 that is recently shown to be important for mycobacterial survival in the presence of antibiotic stressors and limited nutrient condition. In an attempt to find more effective FabG4 inhibitors and its importance in biofilm forming M. tuberculosis, present knowledge about FabG4 and its known inhibitors are discussed. Based on the existing data, a putative role of FabG4 is also suggested.
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spelling pubmed-60085642018-06-26 Advance in Research on Mycobacterium tuberculosis FabG4 and Its Inhibitor Dutta, Debajyoti Front Microbiol Microbiology Increasing evidence from recent reports of drug-resistant mycobacterial strains poses a challenge worldwide. Drug-resistant strains often undergo mutations, adopt alternative pathways, and express drug efflux pumps to reduce or eliminate drug doses. Besides these intrinsic resistance mechanisms, bacteria can evade drug doses by forming biofilms. Biofilms are the concerted growth of adherent microorganisms, which can also be formed at the air-water interface. The growth is supported by the extracellular polymer matrix which is self-produced by the microorganisms. Reduced metabolic activity in a nutrient-deficient environment in the biofilm may cause the microorganisms to take alternative pathways that can make the microorganisms recalcitrant to the drug doses. Recent works have shown that Mycobacterium tuberculosis expresses several proteins during its growth in biofilm, those when deleted, did not show any effect on mycobacterial growth in normal nutrient-sufficient conditions. Studying these unconventional proteins in mycobacterial biofilms is therefore of utmost importance. In this article, I will discuss one such mycobacterial biofilm-related protein FabG4 that is recently shown to be important for mycobacterial survival in the presence of antibiotic stressors and limited nutrient condition. In an attempt to find more effective FabG4 inhibitors and its importance in biofilm forming M. tuberculosis, present knowledge about FabG4 and its known inhibitors are discussed. Based on the existing data, a putative role of FabG4 is also suggested. Frontiers Media S.A. 2018-06-06 /pmc/articles/PMC6008564/ /pubmed/29946302 http://dx.doi.org/10.3389/fmicb.2018.01184 Text en Copyright © 2018 Dutta. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Dutta, Debajyoti
Advance in Research on Mycobacterium tuberculosis FabG4 and Its Inhibitor
title Advance in Research on Mycobacterium tuberculosis FabG4 and Its Inhibitor
title_full Advance in Research on Mycobacterium tuberculosis FabG4 and Its Inhibitor
title_fullStr Advance in Research on Mycobacterium tuberculosis FabG4 and Its Inhibitor
title_full_unstemmed Advance in Research on Mycobacterium tuberculosis FabG4 and Its Inhibitor
title_short Advance in Research on Mycobacterium tuberculosis FabG4 and Its Inhibitor
title_sort advance in research on mycobacterium tuberculosis fabg4 and its inhibitor
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6008564/
https://www.ncbi.nlm.nih.gov/pubmed/29946302
http://dx.doi.org/10.3389/fmicb.2018.01184
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