title: Exposure to a cutinase-like serine esterase triggers rapid lysis of multiple mycobacterial species.
abstract: Mycobacteria are shaped by a thick envelope made of an array of uniquely structured lipids and polysaccharides. However, the spatial organization of these molecules remains unclear. Here, we show that exposure to an esterase from Mycobacterium smegmatis (Msmeg_1529), hydrolyzing the ester linkage of trehalose dimycolate in vitro, triggers rapid and efficient lysis of Mycobacterium tuberculosis, Mycobacterium bovis BCG, and Mycobacterium marinum. Exposure to the esterase immediately releases free mycolic acids, while concomitantly depleting trehalose mycolates. Moreover, lysis could be competitively inhibited by an excess of purified trehalose dimycolate and was abolished by a S124A mutation affecting the catalytic activity of the esterase. These findings are consistent with an indispensable structural role of trehalose mycolates in the architectural design of the exposed surface of the mycobacterial envelope. Importantly, we also demonstrate that the esterase-mediated rapid lysis of M. tuberculosis significantly improves its detection in paucibacillary samples.
authors.affiliation: Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.forename: Alexandra
authors.initials: A
authors.lastname: Bhatti
authors.forename: Danxia
authors.initials: D
authors.lastname: Ke
authors.forename: Mercedes
authors.initials: M
authors.lastname: Gonzalez-Juarrero
authors.forename: Anne
authors.initials: A
authors.lastname: Lenaerts
authors.forename: Laurent
authors.initials: L
authors.lastname: Kremer
authors.forename: Yann
authors.initials: Y
authors.lastname: Guerardel
authors.forename: Peijun
authors.initials: P
authors.lastname: Zhang
authors.forename: Anil K
authors.initials: AK
authors.lastname: Ojha
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000995:Antitubercular Agents / Q000494:pharmacology; D002265:Carboxylic Ester Hydrolases / Q000737:chemistry* / Q000378:metabolism; D002384:Catalysis; D003311:Cord Factors / Q000096:biosynthesis* / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004950:Esterases / Q000737:chemistry* / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D009161:Mycobacterium / Q000201:enzymology*; D014199:Trehalose / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D003311:Cord Factors; D008051:Lipid Bilayers; D008055:Lipids; D000255:Adenosine Triphosphate; D014199:Trehalose; D004950:Esterases; C022635:serine esterase; D002265:Carboxylic Ester Hydrolases; C019952:cutinase