MPL36, a major plasminogen (PLG) receptor in pathogenic Leptospira, has an essential role during infection.

Autor: Zhu W; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America., Passalia FJ; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America.; Laboratory of Vaccine Development, Instituto Butantan, São Paulo, Brazil., Hamond C; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America., Abe CM; Laboratory of Bacteriology, Instituto Butantan, São Paulo, Brazil., Ko AI; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America.; Gonçalo Moniz Institute, Oswaldo Cruz Foundation; Brazilian Ministry of Health; Salvador, Brazil., Barbosa AS; Laboratory of Bacteriology, Instituto Butantan, São Paulo, Brazil., Wunder EA Jr; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, United States of America.; Gonçalo Moniz Institute, Oswaldo Cruz Foundation; Brazilian Ministry of Health; Salvador, Brazil.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2023 Jul 24; Vol. 19 (7), pp. e1011313. Date of Electronic Publication: 2023 Jul 24 (Print Publication: 2023).
DOI: 10.1371/journal.ppat.1011313
Abstrakt: Leptospirosis, a zoonosis with worldwide distribution, is caused by pathogenic spirochetes belonging to the genus Leptospira. Bacterial outer membrane proteins (OMPs), particularly those with surface-exposed regions, play crucial roles in pathogen dissemination and virulence mechanisms. Here we characterized the leptospiral Membrane Protein L36 (MPL36), a rare lipoprotein A (RlpA) homolog with a C-terminal Sporulation related (SPOR) domain, as an important virulence factor in pathogenic Leptospira. Our results confirmed that MPL36 is surface exposed and expressed during infection. Using recombinant MPL36 (rMPL36) we also confirmed previous findings of its high plasminogen (PLG)-binding ability determined by lysine residues of the C-terminal region of the protein, with ability to convert bound-PLG to active plasmin. Using Koch's molecular postulates, we determined that a mutant of mpl36 has a reduced PLG-binding ability, leading to a decreased capacity to adhere and translocate MDCK cell monolayers. Using recombinant protein and mutant strains, we determined that the MPL36-bound plasmin (PLA) can degrade fibrinogen. Finally, our mpl36 mutant had a significant attenuated phenotype in the hamster model for acute leptospirosis. Our data indicates that MPL36 is the major PLG binding protein in pathogenic Leptospira, and crucial to the pathogen's ability to attach and interact with host tissues during infection. The MPL36 characterization contributes to the expanding field of bacterial pathogens that explore PLG for their virulence, advancing the goal to close the knowledge gap regarding leptospiral pathogenesis while offering a novel potential candidate to improve diagnostic and prevention of this important zoonotic neglected disease.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 Zhu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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