Roles of Proteins Containing Immunoglobulin-Like Domains in the Conjugation of Bacterial Plasmids

• Published in: mSphere 2022-02, Vol.7 (1), p.e0097821-e0097821
• Main Authors: Hüttener, Mário, Hergueta, Jon, Bernabeu, Manuel, Prieto, Alejandro, Aznar, Sonia, Merino, Susana, Tomás, Joan, Juárez, Antonio
• Format: Article
• Language: English
• Subjects: Anti-Infective Agents; Antibiotics; Antimicrobial agents; Antimicrobial resistance; Bacteria; Bacteria - genetics; bacterial Ig-like proteins; Cloning; Conjugation; Conjugation, Genetic; E coli; Flagella; Gene Transfer, Horizontal; Genes; Genetic variability; Gram-negative bacteria; Gram-positive bacteria; Horizontal transfer; Immunoglobulin Domains; Immunoglobulins; Microbial Genetics; Organelles; Pili; plasmid conjugation; Plasmids; Plasmids - genetics; Proteins; Public health; Research Article; Salmonella
• ISSN: 2379-5042; 2379-5042
• DOI: 10.1128/msphere.00978-21

Horizontal transfer of bacterial plasmids generates genetic variability and contributes to the dissemination of the genes that enable bacterial cells to develop antimicrobial resistance (AMR). Several aspects of the conjugative process have long been known, namely, those related to the proteins that participate in the establishment of cell-to-cell contact and to the enzymatic processes associated with the processing of plasmid DNA and its transfer to the recipient cell. In this work, we describe the roles of newly identified proteins that influence the conjugation of several plasmids. Genes encoding high-molecular-weight bacterial proteins that contain one or several immunoglobulin-like domains (Big) are located in the transfer regions of several plasmids that usually harbor AMR determinants. These Big proteins are exported to the external medium and target two extracellular organelles: the flagella and conjugative pili. The plasmid gene-encoded Big proteins facilitate conjugation by reducing cell motility and facilitating cell-to-cell contact by binding both to the flagella and to the conjugative pilus. They use the same export machinery as that used by the conjugative pilus components. In the examples characterized in this paper, these proteins influence conjugation at environmental temperatures (i.e., 25°C). This suggests that they may play relevant roles in the dissemination of plasmids in natural environments. Taking into account that they interact with outer surface organelles, they could be targeted to control the dissemination of different bacterial plasmids carrying AMR determinants. Transmission of a plasmid from one bacterial cell to another, in several instances, underlies the dissemination of antimicrobial resistance (AMR) genes. The process requires well-characterized enzymatic machinery that facilitates cell-to-cell contact and the transfer of the plasmid. Our paper identifies novel plasmid gene-encoded high-molecular-weight proteins that contain an immunoglobulin-like domain and are required for plasmid transmission. They are encoded by genes on different groups of plasmids. These proteins are exported outside the cell. They bind to extracellular cell appendages such as the flagella and conjugative pili. Expression of these proteins reduces cell motility and increases the ability of the bacterial cells to transfer the plasmid. These proteins could be targeted with specific antibodies to combat infections caused by AMR microorganisms that ha