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Functional Role of the PE Domain and Immunogenicity of the Mycobacterium tuberculosis Triacylglycerol Hydrolase $LipY^\nabla$

Mishra, Kanhu C and Chastellier, Chantal de and Narayana, Yeddula and Bifani, Pablo and Brown, Alistair K and Besra, Gurdyal S and Katoch, Vishwa M and Joshi, Beenu and Balaji, Kithiganahalli N and Kremer, Laurent (2008) Functional Role of the PE Domain and Immunogenicity of the Mycobacterium tuberculosis Triacylglycerol Hydrolase $LipY^\nabla$. In: Infection and Immunity, 76 (1). pp. 127-140.

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Abstract

PE and PPE proteins appear to be important for virulence and immunopathogenicity in mycobacteria, yet the functions of the PE/PPE domains remain an enigma. To decipher the role of these domains, we have characterized the triacylglycerol (TAG) hydrolase LipY from Mycobacterium tuberculosis, which is the only known PE protein expressing an enzymatic activity. The overproduction of LipY in mycobacteria resulted in a significant reduction in the pool of TAGs, consistent with the lipase activity of this enzyme. Unexpectedly, this reduction was more pronounced in mycobacteria overexpressing LipY lacking the PE domain [LipY( \Delta PE)], suggesting that the PE domain participates in the modulation of LipY activity. Interestingly, Mycobacterium marinum contains a protein homologous to LipY, termed $LipY_{mar}$, in which the PE domain is substituted by a PPE domain. As for LipY, overexpression of $LipY_{mar}$ in Mycobacterium smegmatis significantly reduced the TAG pool, and this was further pronounced when the PPE domain of $LipY_{mar}$ was removed. Fractionation studies and Western blot analysis demonstrated that both LipY and LipY( \Delta PE) were mainly present in the cell wall, indicating that the PE domain was not required for translocation to this site. Furthermore, electron microscopy immunolabeling of LipY( \Delta PE) clearly showed a cell surface localization, thereby suggesting that the lipase may interact with the host immune system. Accordingly, a strong humoral response against LipY and LipY( \Delta PE) was observed in tuberculosis patients. Together, our results suggest for the first time that both PE and PPE domains can share similar functional roles and that LipY represents a novel immunodominant antigen.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to American Society for Microbiology.
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited: 19 Feb 2008
Last Modified: 27 Aug 2008 13:11
URI: http://eprints.iisc.ernet.in/id/eprint/13050

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