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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Perturbation of cytochrome c maturation reveals adaptability of the respiratory chain in Mycobacterium tuberculosis
mBio, Volume 4, No. 5, Article e00475-13, Year 2013
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Description
Mycobacterium tuberculosis depends on aerobic respiration for growth and utilizes an aa3-type cytochrome c oxidase for terminal electron transfer. Cytochrome c maturation in bacteria requires covalent attachment of heme to apocytochrome c, which occurs outside the cytoplasmic membrane. We demonstrate that in M. tuberculosis the thioredoxin-like protein Rv3673c, which we named CcsX, is required for heme insertion in cytochrome c. Inactivation of CcsX resulted in loss of c-type heme absorbance, impaired growth and virulence of M. tuberculosis, and induced cytochrome bd oxidase. This suggests that the bioenergetically less efficient bd oxidase can compensate for deficient cytochrome c oxidase activity, highlighting the flexibility of the M. tuberculosis respiratory chain. A spontaneous mutation in the active site of vitamin K epoxide reductase (VKOR) suppressed phenotypes of the CcsX mutant and abrogated the activity of the disulfide bond-dependent alkaline phosphatase, which shows that VKOR is the major disulfide bond catalyzing protein in the periplasm of M. tuberculosis. © 2013 Small et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3781833/bin/mbo005131624sf01.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3781833/bin/mbo005131624sf02.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3781833/bin/mbo005131624sf03.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3781833/bin/mbo005131624sf04.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3781833/bin/mbo005131624sf05.tif
Authors & Co-Authors
Small, Jennifer L.
Unknown Affiliation
Park, Sae Woong
Unknown Affiliation
Kana, Bavesh Davandra
Unknown Affiliation
Ioerger, Thomas Richard
Unknown Affiliation
Sacchettini, James C.
Unknown Affiliation
Ehrt, Sabine
Unknown Affiliation
Statistics
Citations: 59
Authors: 6
Affiliations: 4
Identifiers
Doi:
10.1128/mBio.00475-13
ISSN:
21612129
e-ISSN:
21507511
Research Areas
Cancer