Chalkophore mediated respiratory oxidase flexibility controls M. tuberculosis virulence
This article has been Reviewed by the following groups
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- Evaluated articles (Rapid Reviews Infectious Diseases)
Abstract
Oxidative phosphorylation has emerged as a critical therapeutic vulnerability of M. tuberculosis , but it is unknown how M. tuberculosis and other pathogens maintain respiration during infection. M. tuberculosis synthesizes diisonitrile lipopeptide chalkophores that chelate copper tightly, but their role in host-pathogen interactions is also unknown. We demonstrate that M. tuberculosis chalkophores maintain the function of the heme-copper bcc:aa 3 respiratory oxidase under copper limitation. Chalkophore deficient M. tuberculosis cannot survive, respire to oxygen, or produce ATP under copper deprivation in culture. M. tuberculosis lacking chalkophore biosynthesis is attenuated in mice, a phenotype that is severely exacerbated by loss of the CytBD alternative respiratory oxidase (encoded by cydAB ), revealing a multilayered flexibility of the respiratory chain that maintains oxidative phosphorylation during infection. Taken together, these data demonstrate that chalkophores counter host inflicted copper deprivation and highlight that protection of cellular respiration is a critical virulence function in M. tuberculosis .
Article activity feed
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Celia Goulding
Review 5: "Chalkophore Mediated Respiratory Oxidase Flexibility Controls M. Tuberculosis Virulence"
Reviewers found the study highly compelling, providing strong evidence for the crucial role of chalkophores in facilitating copper acquisition by Mycobacterium tuberculosis to maintain the function of the heme-copper bcc:aa3 respiratory oxidase.
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William Jacobs
Review 4: "Chalkophore Mediated Respiratory Oxidase Flexibility Controls M. Tuberculosis Virulence"
Reviewers found the study highly compelling, providing strong evidence for the crucial role of chalkophores in facilitating copper acquisition by Mycobacterium tuberculosis to maintain the function of the heme-copper bcc:aa3 respiratory oxidase.
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Tiago Beites
Review 3: "Chalkophore Mediated Respiratory Oxidase Flexibility Controls M. Tuberculosis Virulence"
Reviewers found the study highly compelling, providing strong evidence for the crucial role of chalkophores in facilitating copper acquisition by Mycobacterium tuberculosis to maintain the function of the heme-copper bcc:aa3 respiratory oxidase.
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Sladjana Prišić, Endrei Marcantonio
Review 2: "Chalkophore Mediated Respiratory Oxidase Flexibility Controls M. Tuberculosis Virulence"
Reviewers found the study highly compelling, providing strong evidence for the crucial role of chalkophores in facilitating copper acquisition by Mycobacterium tuberculosis to maintain the function of the heme-copper bcc:aa3 respiratory oxidase.
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Clifton Barry III, Peter J. Finin
Review 1: "Chalkophore Mediated Respiratory Oxidase Flexibility Controls M. Tuberculosis Virulence"
Reviewers found the study highly compelling, providing strong evidence for the crucial role of chalkophores in facilitating copper acquisition by Mycobacterium tuberculosis to maintain the function of the heme-copper bcc:aa3 respiratory oxidase.
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Strength of evidence
Reviewers: C Barry III & P J Finin (NIH) | 📘📘📘📘📘
S Prišić & E Marcantonio (University of Hawaii‘i at Manoa) | 📒📒📒◻️◻️
T Beites (Cornell University) | 📗📗📗📗◻️
W Jacobs (Albert Eienstein College of Medicine) | 📘📘📘📘📘
C Goulding (UC Irvine) |📒📒📒◻️◻️ -
