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Omp19 Enables Brucella abortus to Evade the Antimicrobial Activity From Host's Proteolytic Defense System

Pathogenic microorganisms confront several proteolytic events in the molecular interplay with their host, highlighting that proteolysis and its regulation play an important role during infection. Microbial inhibitors, along with their target endogenous/exogenous enzymes, may directly affect the host...

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Autores principales: Pasquevich, Karina A., Carabajal, Marianela V., Guaimas, Francisco F., Bruno, Laura, Roset, Mara S., Coria, Lorena M., Rey Serrantes, Diego A., Comerci, Diego J., Cassataro, Juliana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6607954/
https://www.ncbi.nlm.nih.gov/pubmed/31297115
http://dx.doi.org/10.3389/fimmu.2019.01436
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author Pasquevich, Karina A.
Carabajal, Marianela V.
Guaimas, Francisco F.
Bruno, Laura
Roset, Mara S.
Coria, Lorena M.
Rey Serrantes, Diego A.
Comerci, Diego J.
Cassataro, Juliana
author_facet Pasquevich, Karina A.
Carabajal, Marianela V.
Guaimas, Francisco F.
Bruno, Laura
Roset, Mara S.
Coria, Lorena M.
Rey Serrantes, Diego A.
Comerci, Diego J.
Cassataro, Juliana
author_sort Pasquevich, Karina A.
collection PubMed
description Pathogenic microorganisms confront several proteolytic events in the molecular interplay with their host, highlighting that proteolysis and its regulation play an important role during infection. Microbial inhibitors, along with their target endogenous/exogenous enzymes, may directly affect the host's defense mechanisms and promote infection. Omp19 is a Brucella spp. conserved lipoprotein anchored by the lipid portion in the Brucella outer membrane. Previous work demonstrated that purified unlipidated Omp19 (U-Omp19) has protease inhibitor activity against gastrointestinal and lysosomal proteases. In this work, we found that a Brucella omp19 deletion mutant is highly attenuated in mice when infecting by the oral route. This attenuation can be explained by bacterial increased susceptibility to host proteases met by the bacteria during establishment of infection. Omp19 deletion mutant has a cell division defect when exposed to pancreatic proteases that is linked to cell-cycle arrest in G1-phase, Omp25 degradation on the cell envelope and CtrA accumulation. Moreover, Omp19 deletion mutant is more susceptible to killing by macrophage derived microsomes than wt strain. Preincubation with gastrointestinal proteases led to an increased susceptibility of Omp19 deletion mutant to macrophage intracellular killing. Thus, in this work, we describe for the first time a physiological function of B. abortus Omp19. This activity enables Brucella to better thrive in the harsh gastrointestinal tract, where protection from proteolytic degradation can be a matter of life or death, and afterwards invade the host and bypass intracellular proteases to establish the chronic infection.
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spelling pubmed-66079542019-07-11 Omp19 Enables Brucella abortus to Evade the Antimicrobial Activity From Host's Proteolytic Defense System Pasquevich, Karina A. Carabajal, Marianela V. Guaimas, Francisco F. Bruno, Laura Roset, Mara S. Coria, Lorena M. Rey Serrantes, Diego A. Comerci, Diego J. Cassataro, Juliana Front Immunol Immunology Pathogenic microorganisms confront several proteolytic events in the molecular interplay with their host, highlighting that proteolysis and its regulation play an important role during infection. Microbial inhibitors, along with their target endogenous/exogenous enzymes, may directly affect the host's defense mechanisms and promote infection. Omp19 is a Brucella spp. conserved lipoprotein anchored by the lipid portion in the Brucella outer membrane. Previous work demonstrated that purified unlipidated Omp19 (U-Omp19) has protease inhibitor activity against gastrointestinal and lysosomal proteases. In this work, we found that a Brucella omp19 deletion mutant is highly attenuated in mice when infecting by the oral route. This attenuation can be explained by bacterial increased susceptibility to host proteases met by the bacteria during establishment of infection. Omp19 deletion mutant has a cell division defect when exposed to pancreatic proteases that is linked to cell-cycle arrest in G1-phase, Omp25 degradation on the cell envelope and CtrA accumulation. Moreover, Omp19 deletion mutant is more susceptible to killing by macrophage derived microsomes than wt strain. Preincubation with gastrointestinal proteases led to an increased susceptibility of Omp19 deletion mutant to macrophage intracellular killing. Thus, in this work, we describe for the first time a physiological function of B. abortus Omp19. This activity enables Brucella to better thrive in the harsh gastrointestinal tract, where protection from proteolytic degradation can be a matter of life or death, and afterwards invade the host and bypass intracellular proteases to establish the chronic infection. Frontiers Media S.A. 2019-06-26 /pmc/articles/PMC6607954/ /pubmed/31297115 http://dx.doi.org/10.3389/fimmu.2019.01436 Text en Copyright © 2019 Pasquevich, Carabajal, Guaimas, Bruno, Roset, Coria, Rey Serrantes, Comerci and Cassataro. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Pasquevich, Karina A.
Carabajal, Marianela V.
Guaimas, Francisco F.
Bruno, Laura
Roset, Mara S.
Coria, Lorena M.
Rey Serrantes, Diego A.
Comerci, Diego J.
Cassataro, Juliana
Omp19 Enables Brucella abortus to Evade the Antimicrobial Activity From Host's Proteolytic Defense System
title Omp19 Enables Brucella abortus to Evade the Antimicrobial Activity From Host's Proteolytic Defense System
title_full Omp19 Enables Brucella abortus to Evade the Antimicrobial Activity From Host's Proteolytic Defense System
title_fullStr Omp19 Enables Brucella abortus to Evade the Antimicrobial Activity From Host's Proteolytic Defense System
title_full_unstemmed Omp19 Enables Brucella abortus to Evade the Antimicrobial Activity From Host's Proteolytic Defense System
title_short Omp19 Enables Brucella abortus to Evade the Antimicrobial Activity From Host's Proteolytic Defense System
title_sort omp19 enables brucella abortus to evade the antimicrobial activity from host's proteolytic defense system
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6607954/
https://www.ncbi.nlm.nih.gov/pubmed/31297115
http://dx.doi.org/10.3389/fimmu.2019.01436
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