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.

[1]  M. Soria,et al.  Characterization of the two component regulatory system PhoPR in Mycobacterium bovis. , 2018, Veterinary microbiology.

[2]  E. Vivés,et al.  Endogenous and Exogenous KdpF Peptide Increases Susceptibility of Mycobacterium bovis BCG to Nitrosative Stress and Reduces Intramacrophage Replication , 2017, Front. Cell. Infect. Microbiol..

[3]  M. Gutierrez,et al.  Mycobacterium bovis Requires P27 (LprG) To Arrest Phagosome Maturation and Replicate within Bovine Macrophages , 2016, Infection and Immunity.

[4]  R. Baker,et al.  The Oxidative Stress Network of Mycobacterium tuberculosis Reveals Coordination between Radical Detoxification Systems. , 2015, Cell host & microbe.

[5]  C. Sassetti,et al.  A Novel P1B-type Mn2+-transporting ATPase Is Required for Secreted Protein Metallation in Mycobacteria* , 2013, The Journal of Biological Chemistry.

[6]  A. Cataldi,et al.  Virulence factors of the Mycobacterium tuberculosis complex , 2013, Virulence.

[7]  D. Kaushal,et al.  Functional Genomics Reveals Extended Roles of the Mycobacterium tuberculosis Stress Response Factor σH , 2009, Journal of bacteriology.

[8]  A. Cataldi,et al.  Immunogenicity and protection induced by Mycobacterium tuberculosis mce-2 and mce-3 mutants in a Balb/c mouse model of progressive pulmonary tuberculosis. , 2006, Vaccine.

[9]  J. McFadden,et al.  Mutation in the P36 gene of Mycobacterium bovis provokes attenuation of the bacillus in a mouse model. , 2005, Tuberculosis.

[10]  W. Jacobs,et al.  The effects of reactive nitrogen intermediates on gene expression in Mycobacterium tuberculosis , 2003, Cellular microbiology.

[11]  Karl W. Broman,et al.  A postgenomic method for predicting essential genes at subsaturation levels of mutagenesis: Application to Mycobacterium tuberculosis , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[12]  E. Rubin,et al.  Genes required for mycobacterial growth defined by high density mutagenesis , 2003, Molecular microbiology.

[13]  P. Gounon,et al.  Attenuation of virulence by disruption of the Mycobacterium tuberculosis erp gene. , 1998, Science.

[14]  W. Purschke,et al.  The terminal quinol oxidase of the hyperthermophilic archaeon Acidianus ambivalens exhibits a novel subunit structure and gene organization , 1997, Journal of bacteriology.

[15]  N. Maulén [Virulence factors of Mycobacterium tuberculosis]. , 2011, Revista medica de Chile.

[16]  A. Cataldi,et al.  Identification of two proteins that interact with the Erp virulence factor from Mycobacterium tuberculosis by using the bacterial two-hybrid system , 2009, BMC Molecular Biology.