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          Institute: MPI für Infektionsbiologie     Collection: Department of Immunology     Display Documents

ID: 529863.0, MPI für Infektionsbiologie / Department of Immunology
An Oligopeptide Transporter of Mycobacterium tuberculosis Regulates Cytokine Release and Apoptosis of Infected Macrophages
Authors:Dasgupta, Arunava; Sureka, Kamakshi; Mitra, Devrani; Saha, Baisakhee; Sanyal, Sourav; Das, Amit K.; Chakrabarti, Parul; Jackson, Mary; Gicquel, Brigitte; Kundu, Manikuntala; Basu, Joyoti
Date of Publication (YYYY-MM-DD):2010-08-17
Title of Journal:PLoS ONE
Journal Abbrev.:PLoS One
Issue / Number:8
Sequence Number of Article:e12225
Copyright:Copyright Dasgupta et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Review Status:Peer-review
Audience:Experts Only
Abstract / Description:Background: The Mycobacterium tuberculosis genome encodes two peptide transporters encoded by Rv3665c-Rv3662c and Rv1280c-Rv1283c. Both belong to the family of ABC transporters containing two nucleotide-binding subunits, two integral membrane proteins and one substrate-binding polypeptide. However, little is known about their functions in M. tuberculosis. Here we report functional characterization of the Rv1280c-Rv1283c-encoded transporter and its substrate-binding polypeptide OppA(MTB). Methodology/Principal Findings: OppA(MTB) was capable of binding the tripeptide glutathione and the nonapeptide bradykinin, indicative of a somewhat broad substrate specificity. Amino acid residues G109, N110, N230, D494 and F496, situated at the interface between domains I and III of OppA, were required for optimal peptide binding. Complementaton of an oppA knockout mutant of M. smegmatis with OppA(MTB) confirmed the role of this transporter in importing glutathione and the importance of the aforesaid amino acid residues in peptide transport. Interestingly, this transporter regulated the ability of M. tuberculosis to lower glutathione levels in infected compared to uninfected macrophages. This ability was partly offset by inactivation of oppD. Concomitantly, inactivation of oppD was associated with lowered levels of methyl glyoxal in infected macrophages and reduced apoptosis-inducing ability of the mutant. The ability to induce the production of the cytokines IL-1 beta, IL-6 and TNF-alpha was also compromised after inactivation of oppD. Conclusions: Taken together, these studies uncover the novel observations that this peptide transporter modulates the innate immune response of macrophages infected with M. tuberculosis.
External Publication Status:published
Document Type:Article
Communicated by:Hilmar Fünning
Affiliations:MPI für Infektionsbiologie/Department of Immunology
External Affiliations:Inst Pasteur, Unite Genet Mycobacterienne, Paris, France.; ] Bose Inst, Dept Chem, Calcutta, India.; Indian Inst Technol, Dept Biotechnol, Kharagpur 721302, W Bengal, India.
Identifiers:ISI:000280968100023 [ID No:1]
ISSN:1932-6203 [ID No:2]
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