1887

Abstract

PE11 (Rv1169c or LipX) is a cell wall associated esterase/lipase of (Mtb). Evidences suggest that PE11 is expressed by Mtb both and . Previous studies have shown that PE11 leads to modification in cell wall lipid content and enhanced virulence when expressed in the non-pathogenic surrogate . Since cell wall lipids often play different roles in pathogenic and non-pathogenic mycobacteria, we investigated the role of PE11 in its host, Mtb. Mtb with lowered expression of PE11 (PE11 knock-down) displayed significant changes in colony morphology and cell wall lipid profile, confirming the role of PE11 in cell wall architecture. In addition, the levels of phthiocerol dimycocerosates, a cell wall virulence factor, were decreased. Levels of trehalose esters and free mycolic acids were increased. In contrast to expressing Mtb PE11, a role reversal was observed in Mtb with respect to pellicle/biofilm formation. The PE11 knock-down Mtb strain showed significantly enhanced aggregation and early biofilm growth in detergent-free medium, compared to the wild-type. Knock-down strain also showed nearly 27-fold up-regulation of a fibronectin attachment protein (Rv1759c), linking biofilm growth with over-expression of bacterial proteins that help in aggregation and/or binding to host extracellular matrix. The knock-down also resulted in poor virulence of Mtb in PMA (phorbol 12-myristate 13-acetate) treated and PMA+IFN-γ treated THP-1 macrophages. Therefore, the study not only links PE11 to cell wall virulence lipids but also reveals the involvement of this cell wall associated esterase in down-regulation of biofilm in Mtb.

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2017-01-01
2020-01-20
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