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Citrate lyase CitE in Mycobacterium tuberculosis contributes to mycobacterial survival under hypoxic conditions
Mycobacterium tuberculosis is the causative agent of tuberculosis and has evolved an ability to survive in hostile host environments. M. tuberculosis is thought to utilize the rTCA cycle to sustain its latent growth during infection, but the enzymatic characteristics and physiological function for t...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164622/ https://www.ncbi.nlm.nih.gov/pubmed/32302313 http://dx.doi.org/10.1371/journal.pone.0230786 |
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author | Hu, Jialing Jin, Kaixi He, Zheng-Guo Zhang, Hua |
author_facet | Hu, Jialing Jin, Kaixi He, Zheng-Guo Zhang, Hua |
author_sort | Hu, Jialing |
collection | PubMed |
description | Mycobacterium tuberculosis is the causative agent of tuberculosis and has evolved an ability to survive in hostile host environments. M. tuberculosis is thought to utilize the rTCA cycle to sustain its latent growth during infection, but the enzymatic characteristics and physiological function for the key citrate lyase of the rTCA cycle, MtbCitE, in the important pathogen remain unclear. In this study, we investigated the function of MtbCitE based on its structural properties and sequence comparisons with other bacterial citrate lyase subunits. We showed that several amino acid residues were important for the citrate cleavage activity of MtbCitE. Strikingly, the citrate cleavage activity of MtbCitE was inhibited by ATP, indicating that energy metabolism might couple with the regulation of MtbCitE activity, which differed from other CitEs. More interestingly, deletion of citE from Mycobacterium bovis BCG decreased the mycobacterial survival rate under hypoxic conditions, whereas complementation with citE restored the phenotype to wild-type levels. Consistently, three key rTCA cycle enzymes were positively regulated under hypoxic conditions in mycobacteria. Therefore, we characterized a unique citrate lyase MtbCitE from M. tuberculosis and found that the CitE protein significantly contributed to mycobacterial survival under hypoxic conditions. |
format | Online Article Text |
id | pubmed-7164622 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-71646222020-04-22 Citrate lyase CitE in Mycobacterium tuberculosis contributes to mycobacterial survival under hypoxic conditions Hu, Jialing Jin, Kaixi He, Zheng-Guo Zhang, Hua PLoS One Research Article Mycobacterium tuberculosis is the causative agent of tuberculosis and has evolved an ability to survive in hostile host environments. M. tuberculosis is thought to utilize the rTCA cycle to sustain its latent growth during infection, but the enzymatic characteristics and physiological function for the key citrate lyase of the rTCA cycle, MtbCitE, in the important pathogen remain unclear. In this study, we investigated the function of MtbCitE based on its structural properties and sequence comparisons with other bacterial citrate lyase subunits. We showed that several amino acid residues were important for the citrate cleavage activity of MtbCitE. Strikingly, the citrate cleavage activity of MtbCitE was inhibited by ATP, indicating that energy metabolism might couple with the regulation of MtbCitE activity, which differed from other CitEs. More interestingly, deletion of citE from Mycobacterium bovis BCG decreased the mycobacterial survival rate under hypoxic conditions, whereas complementation with citE restored the phenotype to wild-type levels. Consistently, three key rTCA cycle enzymes were positively regulated under hypoxic conditions in mycobacteria. Therefore, we characterized a unique citrate lyase MtbCitE from M. tuberculosis and found that the CitE protein significantly contributed to mycobacterial survival under hypoxic conditions. Public Library of Science 2020-04-17 /pmc/articles/PMC7164622/ /pubmed/32302313 http://dx.doi.org/10.1371/journal.pone.0230786 Text en © 2020 Hu et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Hu, Jialing Jin, Kaixi He, Zheng-Guo Zhang, Hua Citrate lyase CitE in Mycobacterium tuberculosis contributes to mycobacterial survival under hypoxic conditions |
title | Citrate lyase CitE in Mycobacterium tuberculosis contributes to mycobacterial survival under hypoxic conditions |
title_full | Citrate lyase CitE in Mycobacterium tuberculosis contributes to mycobacterial survival under hypoxic conditions |
title_fullStr | Citrate lyase CitE in Mycobacterium tuberculosis contributes to mycobacterial survival under hypoxic conditions |
title_full_unstemmed | Citrate lyase CitE in Mycobacterium tuberculosis contributes to mycobacterial survival under hypoxic conditions |
title_short | Citrate lyase CitE in Mycobacterium tuberculosis contributes to mycobacterial survival under hypoxic conditions |
title_sort | citrate lyase cite in mycobacterium tuberculosis contributes to mycobacterial survival under hypoxic conditions |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164622/ https://www.ncbi.nlm.nih.gov/pubmed/32302313 http://dx.doi.org/10.1371/journal.pone.0230786 |
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