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Lipoprotein, LprI, of Mycobacterium tuberculosis acts as a lysozyme inhibitor.

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title Lipoprotein, LprI, of Mycobacterium tuberculosis acts as a lysozyme inhibitor.
 
Creator Sethi, Deepti
Mahajan, Sahil
Singh, Chaahat
Lama, Amrita
Hade, Mangesh Dattu
Gupta, Pawan
Dikshit, Kanak L
 
Subject QR Microbiology
 
Description Mycobacterium tuberculosis (Mtb) executes numerous defence strategies for the successful establishment of infection under diverse array of challenges inside the host. One such strategy that has been delineated in this study is the abrogation of lytic activity of lysozyme by a novel glycosylated and surface localized lipoprotein, LprI, which is exclusively present in Mtb complex. The lprI gene co-transcribes with the glbN gene (encoding hemoglobin, HbN) and both are synchronously up-regulated in Mtb during macrophage infection. Recombinant LprI, expressed in E. coli, exhibited strong binding (Kd ≤ 2 nM) with lysozyme and abrogated its lytic activity completely, thereby conferring protection to fluorescein labelled protected its growth from lysozyme inhibition in vitro and enhanced its phagocytosis Micrococcus lysodeikticus from lysozyme mediated hydrolysis. Expression of the lprI gene in M. smegmatis (8-10 folds) and survival during intracellular infection of peritoneal and monocyte derived macrophages, known to secrete lysozyme, and also in the presence of exogenously added lysozyme in secondary cell lines where lysozyme levels are low. In contrast, the presence of HbN enhanced phagocytosis and intracellular survival of M. smegmatis only in the absence of lysozyme but not under lysozyme stress. Interestingly, co-expression of glbN-lprI gene pair elevated the invasion and survival of M. smegmatis 2 to 3 folds in secondary cell lines in the presence of lysozyme in comparison to isogenic cells, expressing these genes individually. Thus, specific advantage against macrophage generated lysozyme, conferred by the combination of LprI-HbN during invasion of Mtb, may have vital implications on pathogenesis of tuberculosis.
 
Publisher ASBMB
 
Date 2015-11-20
 
Type Article
PeerReviewed
 
Relation http://www.jbc.org/lookup/pmid?view=long&pmid=26589796
http://crdd.osdd.net/open/1811/
 
Identifier Sethi, Deepti and Mahajan, Sahil and Singh, Chaahat and Lama, Amrita and Hade, Mangesh Dattu and Gupta, Pawan and Dikshit, Kanak L (2015) Lipoprotein, LprI, of Mycobacterium tuberculosis acts as a lysozyme inhibitor. The Journal of biological chemistry. ISSN 1083-351X