SadA, a Trimeric Autotransporter from Salmonella enterica Serovar Typhimurium, Can Promote Biofilm Formation and Provides Limited Protection against Infection

Abstract

Salmonella enterica is a major cause of morbidity worldwide and mortality in children and immunocompromised individuals in sub-Saharan Africa. Outer membrane proteins of Salmonella are of significance because they are at the interface between the pathogen and the host, they can contribute to adherence, colonization, and virulence, and they are frequently targets of antibody-mediated immunity. In this study, the properties of SadA, a purported trimeric autotransporter adhesin of Salmonella enterica serovar Typhimurium, were examined. We demonstrated that SadA is exposed on the Salmonella cell surface in vitro and in vivo during infection of mice. Expression of SadA resulted in cell aggregation, biofilm formation, and increased adhesion to human intestinal Caco-2 epithelial cells. Immunization of mice with folded, full-length, purified SadA elicited an IgG response which provided limited protection against bacterial challenge. When anti-SadA IgG titers were enhanced by administering alum-precipitated protein, a modest additional protection was afforded. Therefore, despite SadA having pleiotropic functions, it is not a dominant, protective antigen for antibody-mediated protection against Salmonella.

Complete fiber structures of complex trimeric autotransporter adhesins conserved in enterobacteria

“…This protein is called SadA in Salmonella enterica (22), EhaG in enteropathogenic Escherichia coli (EHEC), and UpaG in uropathogenic E. coli (UPEC). UpaG has been found to be essential for the colonization of the urinary tract by UPEC (23), whereas EhaG mediates binding of EHEC specifically to colorectal epithelium (24); SadA promotes biofilm formation and host cell adherence in Salmonella (25). Here, we reconstruct the full SadA, UpaG, and EhaG fibers from the structures of representative SadA fragments, describing in the process a number of unusual structural motifs with functional implications.…”

Characterization and Functional Analysis of AatB, a Novel Autotransporter Adhesin and Virulence Factor of Avian Pathogenic Escherichia coli

“…*, P Ͻ 0.05; **, P Ͻ 0.01. of adhesion to the lifestyle of bacteria is reflected by the wide range of different adhesins found even in a single species. AT proteins are nonfimbrial adhesins and promote adhesion of bacteria (10,21,39). Therefore, we determined whether AatB could mediate adhesion, aggregation, and biofilm formation.…”

“…A new member of the TAA family, UpaG, has been identified in uropathogenic E. coli (UPEC) and promotes cellular aggregation and biofilm formation in strain CFT073 (33). SadA, a TAA from Salmonella enterica serovar Typhimurium, promotes biofilm formation and provides limited protection against infection (10).…”

“…All TAA proteins identified to date display bacterial adherence, adhesion, and aggregation activities to mediate bacterial interactions with either host cells or extracellular matrix (ECM) proteins. The conventional ATs are involved in the adhesion, cytotoxicity, and lipase or protease activities of bacteria (4,7,8,(10)(11)(12)(13)(14)(15).…”

The Haemophilus Cryptic Genospecies Cha Adhesin Has at Least Two Variants That Differ in Host Cell Binding, Bacterial Aggregation, and Biofilm Formation Properties

“…Subsequently, the short outer membrane anchor trimerizes to create a 12-stranded ␤-barrel pore that facilitates export of the trimeric passenger domain across the outer membrane, resulting in attachment of the passenger domain to the membrane anchor on the bacterial surface. Many TAA family members appear to have more than one role in pathogenesis and can be involved in adherence to host cells, the formation of biofilms, and evasion of the immune system (12)(13)(14)(15). While the ␤-barrel domain is the only conserved portion among the TAA family, all members described to date have adhesive activity and share a repetitive structural domain organization, typically a coiled-coil stalk and a spherical adhesive tip (16).…”