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Rv2617c and P36 are virulence factors of pathogenic mycobacteria involved in resistance to oxidative stress.

ABSTRACT: In this study, we characterized the role of Rv2617c in the virulence of Mycobacterium tuberculosis. Rv2617c is a protein of unknown function unique to M. tuberculosis complex (MTC) and Mycobacterium leprae. In vitro, this protein interacts with the virulence factor P36 (also named Erp) and KdpF, a protein linked to nitrosative stress. Here, we showed that knockout of the Rv2617c gene in M. tuberculosis CDC1551 reduced the replication of the pathogen in a mouse model of infection and favored the trafficking of mycobacteria to phagolysosomes. We also demonstrated that Rv2617c and P36 are required for resistance to in vitro hydrogen peroxide treatment in M. tuberculosis and Mycobacterium bovis, respectively. These findings indicate Rv2617c and P36 act in concert to prevent bacterial damage upon oxidative stress.

SUBMITTER: Forrellad MA

PROVIDER: S-EPMC6930017 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Rv2617c and P36 are virulence factors of pathogenic mycobacteria involved in resistance to oxidative stress.

Forrellad Marina A MA Vázquez Cristina L CL Blanco Federico C FC Klepp Laura I LI García Elizabeth A EA Rocha Rosana V RV Luciana Villafañe V Bigi María M MM Gutierrez Maximiliano G MG Bigi Fabiana F

Virulence 20191201 1

In this study, we characterized the role of Rv2617c in the virulence of Mycobacterium tuberculosis. Rv2617c is a protein of unknown function unique to M. tuberculosis complex (MTC) and Mycobacterium leprae. In vitro, this protein interacts with the virulence factor P36 (also named Erp) and KdpF, a protein linked to nitrosative stress. Here, we showed that knockout of the Rv2617c gene in M. tuberculosis CDC1551 reduced the replication of the pathogen in a mouse ...[more]

PMID: 31782338

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Project description:Cryptococcus neoformans is an important pathogen that annually kills 200,000 people worldwide. It survives in the environment as a yeast or spore and can also proliferate within host macrophages after being inhaled into the lungs. In conditions of immunocompromise, cryptococcal cells can escape from the lungs to the brain, where they cause a deadly meningoencephalitis that is both difficult and expensive to treat. Cryptococcal adaptation to the harsh lung environment is a critical first step in its pathogenesis, and consequently a compelling topic of study. This adaptation is mediated by a complex transcriptional program that integrates cellular responses to environmental stimuli. Although several key regulators in this process have been examined, one important protein complex that modulates transcription yet remains understudied in C. neoformans is the Mediator complex. In other organisms, this complex promotes transcription of specific genes by increasing the assembly of the RNA Polymerase II pre-initiation complex. We have focused on the Kinase Module of the Mediator complex, which consists of cyclin C (Ssn801), cyclin-dependent kinase 8 (Cdk8), and two other proteins (Med12 and Med13). This module provides important inhibitory control of Mediator complex assembly and activity. Using a transcriptomics approach, we discovered that Cdk8 and Ssn801 together regulate cryptococcal functions relevant to pathogenesis, including the response to oxidative stress. Deletion of CDK8 resulted in altered mitochondrial morphology and the dysregulation of genes involved in oxidation-reduction processes, such that this strain exhibited increased susceptibility to oxidative stress. This resulted in an inability of mutant cells to proliferate within phagocytes, decreased lung burdens, and attenuated virulence in in vivo studies. These findings increase our understanding of cryptococcal adaptation to the host environment and its regulation of oxidative stress resistance and virulence.

Dataset Information

Rv2617c and P36 are virulence factors of pathogenic mycobacteria involved in resistance to oxidative stress.

Publications

Rv2617c and P36 are virulence factors of pathogenic mycobacteria involved in resistance to oxidative stress.

Similar Datasets

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