Department of Genetics, Microbiology and Statistics, University of Barcelona, Barcelona, Spain
Luïsa Miró
Department of Biochemistry and Physiology, Universitat de Barcelona, Barcelona, Spain; Institut de Nutrició i Seguretat Alimentària, Universitat de Barcelona, Barcelona, Spain
Yago Margolles
Department of Microbial Biotechnology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB-CSIC), Madrid, Spain
Manuel Bernabeu
Department of Genetics, Microbiology and Statistics, University of Barcelona, Barcelona, Spain
David Salguero
Department of Genetics, Microbiology and Statistics, University of Barcelona, Barcelona, Spain
Susana Merino
Department of Genetics, Microbiology and Statistics, University of Barcelona, Barcelona, Spain
Joan Tomas
Department of Genetics, Microbiology and Statistics, University of Barcelona, Barcelona, Spain
Instituto Universitario de Investigaciones Biomédicas y Sanitarias (IUIBS), Facultad de Veterinaria, Universidad de Las Palmas de Gran Canaria (ULPGC), Campus Universitario de Arucas, Las Palmas, Spain
Department of Biochemistry and Physiology, Universitat de Barcelona, Barcelona, Spain; Institut de Nutrició i Seguretat Alimentària, Universitat de Barcelona, Barcelona, Spain
Mario Huttener
Department of Genetics, Microbiology and Statistics, University of Barcelona, Barcelona, Spain
Luis Ángel Fernández
Department of Microbial Biotechnology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB-CSIC), Madrid, Spain
Department of Genetics, Microbiology and Statistics, University of Barcelona, Barcelona, Spain; Institute for Bioengineering of Catalonia, The Barcelona Institute of Science and Technology, Barcelona, Spain
Antimicrobial resistance (AMR) poses a significant threat to human health. Although vaccines have been developed to combat AMR, it has proven challenging to associate specific vaccine antigens with AMR. Bacterial plasmids play a crucial role in the transmission of AMR. Our recent research has identified a group of bacterial plasmids (specifically, IncHI plasmids) that encode large molecular mass proteins containing bacterial immunoglobulin-like domains. These proteins are found on the external surface of the bacterial cells, such as in the flagella or conjugative pili. In this study, we show that these proteins are antigenic and can protect mice from infection caused by an AMR Salmonella strain harboring one of these plasmids. Furthermore, we successfully generated nanobodies targeting these proteins, that were shown to interfere with the conjugative transfer of IncHI plasmids. Considering that these proteins are also encoded in other groups of plasmids, such as IncA/C and IncP2, targeting them could be a valuable strategy in combating AMR infections caused by bacteria harboring different groups of AMR plasmids. Since the selected antigens are directly linked to AMR itself, the protective effect extends beyond specific microorganisms to include all those carrying the corresponding resistance plasmids.
