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

• Published in: Frontiers in immunology Vol. 10; p. 1436
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 26.06.2019
• Subjects: bacterial protease inhibitor; brucellosis; gastrointestinal route of infection; Immunology; intracellular proteases; Omp19; bacterial protease inhibitor; intracellular proteases; Omp19; gastrointestinal route of infection; brucellosis
• DOI: 10.3389/fimmu.2019.01436
• ISSN: 1664-3224

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 spp. conserved lipoprotein anchored by the lipid portion in the 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 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 Omp19. This activity enables 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.