Identification of Type VI Secretion Systems Effector Proteins That Contribute to Interbacterial Competition in Salmonella Dublin

Abstract

The Type VI Secretion System (T6SS) is a multiprotein device that has emerged as an important fitness and virulence factor for many Gram-negative bacteria through the injection of effector proteins into prokaryotic or eukaryotic cells via a contractile mechanism. While some effector proteins specifically target bacterial or eukaryotic cells, others can target both types of cells (trans-kingdom effectors). In Salmonella, five T6SS gene clusters have been identified within pathogenicity islands SPI-6, SPI-19, SPI-20, SPI-21, and SPI-22, which are differentially distributed among serotypes. Salmonella enterica serotype Dublin (S. Dublin) is a cattle-adapted pathogen that harbors both T6SSSPI-6 and T6SSSPI-19. Interestingly, while both systems have been linked to virulence and host colonization in S. Dublin, an antibacterial activity has not been detected for T6SSSPI-6 in this serotype. In addition, there is limited information regarding the repertoire of effector proteins encoded within T6SSSPI-6 and T6SSSPI-19 gene clusters in S. Dublin. In the present study, we demonstrate that T6SSSPI-6 and T6SSSPI-19 of S. Dublin CT_02021853 contribute to interbacterial competition. Bioinformatic and comparative genomic analyses allowed us to identify genes encoding three candidate antibacterial effectors located within SPI-6 and two candidate effectors located within SPI-19. Each antibacterial effector gene is located upstream of a gene encoding a hypothetic immunity protein, thus conforming an effector/immunity (E/I) module. Of note, the genes encoding these effectors and immunity proteins are widely distributed in Salmonella genomes, suggesting a relevant role in interbacterial competition and virulence. Finally, we demonstrate that E/I modules SED_RS01930/SED_RS01935 (encoded in SPI-6), SED_RS06235/SED_RS06230, and SED_RS06335/SED_RS06340 (both encoded in SPI-19) contribute to interbacterial competition in S. Dublin CT_02021853.

Serotypes, Antibiotic Resistance Genes, and Salmonella Pathogenicity Island Genes of Salmonella from Patients in a Hospital in Weifang, China

“…SPI3 and SPI4 aid Salmonella survival and adherence to the surface of polarized cells, while SPI5 encodes an effector protein released via the type III secretion system encoded by SPI1 and SPI2 (25). Also, SPI6 encodes type VI secret system-related proteins (26). These virulence factors aid Salmonella invasion, reproduction, virulence, and transmission in a complex environment (27).…”

Manipulation of host immune defenses by effector proteins delivered from multiple secretion systems of Salmonella and its application in vaccine research

“…The deletion of SPI-19 in these serotypes significantly affects the survival and colonization of Salmonella in cells and organs, and induces fast bacterial clearance. The SPI-19 deleted strain of S. Dublin also competed significantly weaker than the wild-type strain when co-cultured with strains of pathogenic E. coli, suggesting that this T6SS plays an important role in pathogenicity by killing commensal bacteria in the intestine (30,31). S. Typhimurium harbors a T6SS encoded in SPI-6, which contributes to the capability of Salmonella to colonize mice (32).…”

Facultative bacterial symbionts from European Orius species: Evidence for an ancestral symbiotic association

“…The classification of T6SS subtype is i3 in these Serratia sp. Orius isolates, and it is associated with interbacterial competition (Amaya et al, 2022). Salmonella enterica serotype Dublin (S. Dublin) is a cattleadapted pathogen that harbours both T6SS_SPI-6 and T6SS_SPI-19 and both systems have been linked to virulence and host colonization in S. Dublin.…”

“…Salmonella enterica serotype Dublin (S. Dublin) is a cattleadapted pathogen that harbours both T6SS_SPI-6 and T6SS_SPI-19 and both systems have been linked to virulence and host colonization in S. Dublin. T6SSSPI-6 belongs to subtype i3 and encoding three candidate antibacterial effectors located within SPI-6 (Amaya et al, 2022).…”

“…Each antibacterial effector gene is located upstream of a gene encoding a hypothetic immunity protein, thus conforming an effector/immunity (E/I) module. Of note, the genes encoding these effectors and immunity proteins are widely distributed in Salmonella genomes, it was suggesting a relevant role in interbacterial competition and virulence (Amaya et al, 2022). In Serratia sp.…”