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

Author:

Raghunathan Dhaarini1,Wells Timothy J.1,Morris Faye C.1,Shaw Robert K.2,Bobat Saeeda1,Peters Sarah E.3,Paterson Gavin K.3,Jensen Karina Tveen1,Leyton Denisse L.1,Blair Jessica M. A.1,Browning Douglas F.1,Pravin John1,Flores-Langarica Adriana1,Hitchcock Jessica R.1,Moraes Claudia T. P.4,Piazza Roxane M. F.4,Maskell Duncan J.3,Webber Mark A.1,May Robin C.5,MacLennan Calman A.1,Piddock Laura J.1,Cunningham Adam F.1,Henderson Ian R.1

Affiliation:

1. School of Immunity and Infection, University of Birmingham, Birmingham, United Kingdom

2. Centre for Molecular Microbiology and Infection, Imperial College London, London, United Kingdom

3. Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom

4. Laboratory of Bacteriology, Butantan Institute, São Paulo, Brazil

5. School of Biosciences, University of Birmingham, Birmingham, United Kingdom

Abstract

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 .

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Immunology,Microbiology,Parasitology

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