A genomic island in Brucella involved in the adhesion to host cells: Identification of a new adhesin and a translocation factor

Abstract

Adhesion to host cells is the first step in the virulence cycle of any pathogen. In Gram-negative bacteria, adhesion is mediated, among other virulence factors such as the lipopolysaccharides, by specific outer-membrane proteins generally termed adhesins that belong to a wide variety of families and have different evolutionary origins. In Brucella, a widespread zoonotic pathogen of animal and human health concern, adhesion is central as it may determine the intracellular fate of the bacterium, an essential stage in its pathogenesis. In the present paper, we further characterised a genomic locus that we have previously reported encodes an adhesin (BigA) with a bacterial immunoglobulin-like domain (BIg-like). We found that this region encodes a second adhesin, which we have named BigB; and PalA, a periplasmic protein necessary for the proper display in the outer membrane of BigA and BigB. Deletion of bigB or palA diminishes the adhesion of the bacterium and overexpression of BigB dramatically increases it. Incubation of cells with the recombinant BIg-like domain of BigB induced important cytoskeletal rearrangements and affected the focal adhesion sites indicating that the adhesin targets cell-cell or cell-matrix proteins. We additionally show that PalA has a periplasmic localisation and is completely necessary for the proper display of BigA and BigB, probably avoiding their aggregation and facilitating their transport to the outer membrane. Our results indicate that this genomic island is entirely devoted to the adhesion of Brucella to host cells.

Adhesive Functions or Pseudogenization of Type Va Autotransporters in Brucella Species

“…To invade cells, bacteria must be able to adhere to the cell surface. In fact, several adhesins have been shown to participate in adhesion and/or invasion to host cells, including the BmaC type Va autotransporter and the BtaE and BtaF trimeric autotransporters (Castaneda-Roldan et al, 2006;Czibener and Ugalde, 2012;Posadas et al, 2012;Ruiz-Ranwez et al, 2013a;Ruiz-Ranwez et al, 2013b;Czibener et al, 2016;Bialer et al, 2020;Lopez et al, 2020).…”

“…Interestingly, addition of recombinant BigA or BigB proteins to cells induces cytoskeleton rearrangements and affects focal adhesion sites. The authors proposed that the Big adhesins target cell-cell junctions or ECM proteins (Czibener et al, 2016;Lopez et al, 2020). One possibility is that both Big and Bma adhesins could play complementary roles in adhesion to epithelial cells either directly or through ECM components.…”

Brucella Phagocytosis Mediated by Pathogen-Host Interactions and Their Intracellular Survival

“…These molecules regulate Brucella adhesion to host cell surface molecules and extracellular matrix components. In addition to ensuring the adhesion of Brucella to the host cell surface, these adhesins are considered immunogens or vaccine candidates to activate host immunity [ 12 , 13 , 14 , 15 , 16 , 17 ]. A study by Castaneda-Roldan et al [ 16 ] displayed that a Brucella surface protein SP41 can bind selectively to epithelial HeLa cells.…”

Brucella Egresses from Host Cells Exploiting Multivesicular Bodies

“… Brucella , a member of this group of pathogens, is an intracellular bacterium that causes brucellosis, a widespread zoonosis that affects livestock and humans, particularly in areas of endemicity ( 4 , 5 ). The virulence of this pathogen is completely dependent on its capacity to replicate in host cells, a process that involves adhesion ( 6 – 8 ), the invasion of the cell, the evasion of phagolysosome fusion ( 9 – 11 ), and the establishment of an intracellular replication niche ( 9 ). These processes are highly regulated by bacterial virulence factors that modulate host cellular responses to promote microbial survival and replication ( 5 , 12 ).…”