Rv0807, a putative phospholipase A2 of <i>Mycobacterium tuberculosis</i>; Elucidation through sequence analysis, homology modeling, molecular docking and molecular dynamics studies of potential substrates and inhibitors

Sundar, Shobana; Thangamani, Lokesh; Manivel, Gowdham; Kumar, Praveen; Shanmughavel, P.

doi:10.1080/07391102.2019.1677499

Cited by 1 publication

(2 citation statements)

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“…A few previous reports, which described the PLA in Mtb, mainly focused on activity and structural research, and there are no data currently available regarding PLP activity and pathogenicity ( Parker et al, 2007 , 2009 ; Sundar et al, 2019 ). In our investigation, we have, for the first time, successfully constructed a Rv3091 recombinant M. smegmatis (Ms3091) and identified that the extracellular activity of Rv3091 promoted escape from the phagosome and intracellular survival of M. smegmatis .…”

Section: Discussionmentioning

confidence: 99%

“…Phospholipases catalyze the hydrolysis of phospholipids, which are common in mammalian membrane structures, to release fatty acids and a phosphoric acid mixture (Flores-Diaz et al, 2016;Hiller et al, 2018;Wilson and Knoll, 2018). Thus, Mtb phospholipases may play a crucial role in generating cell wall (CW) components and are necessary for Mtb adaptation and survival within macrophages, especially in blocking phagosomal maturation and killing (Santucci et al, 2018b;Sundar et al, 2019). The free fatty acids hydrolyzed by phospholipases provide an energy source for Mtb to grow and replicate in cells (Rameshwaram et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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Rv3091, An Extracellular Patatin-Like Phospholipase in Mycobacterium tuberculosis, Prolongs Intracellular Survival of Recombinant Mycolicibacterium smegmatis by Mediating Phagosomal Escape

et al. 2020

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Patatin-like phospholipases (PLPs) are important virulence factors of many pathogens. However, there are no prevailing studies regarding PLPs as a virulence factor of Mycobacterium tuberculosis (Mtb). Analysis of Rv3091, a putative protein of Mtb, shows that it belongs to the PLPs family. Here, we cloned and expressed the rv3091 gene in Mycobacterium smegmatis and, subsequently, conducted protein purification and characterization. We show that it possesses phospholipase A 1 , phospholipase A 2 , and lipase activity. We confirm the putative active site residues, namely, Ser214 and Asp407, using site directed mutagenesis. The Rv3091 is an extracellular protein that alters the colony morphology of M. smegmatis. The presence of Rv3091 enhances the intracellular survival capability of M. smegmatis in murine peritoneal macrophages. Additionally, it promotes M. smegmatis phagosomal escape from macrophages. Moreover, Rv3091 significantly increased the survival of M. smegmatis and aggravated lesions in C57BL/6 J murine lungs in vivo. Taken together, our results indicate that Rv3091 as an extracellular PLP that is critical to the pathogenicity of mycobacterium as it allows mycobacterium to utilize phospholipids for its growth and provides resistance to phagosome killing, resulting in its enhanced intracellular survival.

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Section: Discussionmentioning

confidence: 99%