‘Form variation’ of the O12 antigen is critical for persistence of Salmonella Typhimurium in the murine intestine

Abstract

SummarySalmonella enterica subspecies I serotypes are responsible for the vast majority of salmonellosis in mammals and birds, yet only a few factors specific to this group that allow them to persist in this niche have been identified. We show that STM0557, a S. enterica subspecies I-specific gene encoding an inner membrane protein, is critical for faecal shedding and intestinal persistence of S. enterica serotype Typhimurium ATCC14028 in Salmonella-resistant mice, but mutations in this gene do not diminish short-term intestinal colonization or invasion of cultured epithelial cells. STM0557 and two neighbouring genes, located on a pathogenicity island termed SPI-16, resemble genes of the gtrA,B, gtr(type) cluster in seroconverting bacteriophages. In general, the gtr genes encode proteins responsible for serotype conversion of the infected bacterium by addition glucose residues to repeating O-antigen subunits of lipopolysaccharide (LPS). In lysogenized Shigella, such modifications have been previously shown to be constitutively expressed and to facilitate invasion of host cells. We show that serotype Typhimurium gtr orthologues, STM0557-0559, are responsible for 'form variation' or glucosylation of the O12 antigen galactose (4 position) to generate the 12-2 variant. Form variation in Typhimurium is not constitutive, but occurred upon exposure and during intracellular growth of serotype Typhimurium in J774 macrophages. Our data suggest that the 12-2 antigen is a S. enterica subspecies I-specific LPS modification that enhances long-term intestinal colonization, and is in contrast to the role of O-antigen variation described for Shigella.

Infection of Mice by Salmonella enterica Serovar Enteritidis Involves Additional Genes That Are Absent in the Genome of Serovar Typhimurium

“…Finally, the genes SEN0535 and SEN0536 within SPI-16 also were negatively selected during S. Enteritidis infection of mice. We have shown previously that the orthologous genes in S. Typhimurium are responsible for the "form variation" of the O12 antigen to generate the 12-2 variant that is critical for the persistence of this serovar in the murine intestine (15).…”

Genomic Variability of Serial Human Isolates of Salmonella enterica Serovar Typhimurium Associated with Prolonged Carriage

“…The isolates from two patients (patients 5 and 7) did not contain the virulence plasmid pSLT (18). Several virulence factors are known to play a role in fecal shedding or the carrier state, including genes encoding thin aggregative fimbriae (19), genes encoding the secreted effectors ShdA and MisL (20,21), and genes located on Salmonella pathogenicity island 16 that are responsible for O-antigen glycosylation (22). The isolates analyzed in this study were all found to carry these genes, but none of these genes carried mutations in isolates from the same patient, suggesting that no further adaptive changes in these genes occurred during carriage.…”

Bacteriophage-mediated Glucosylation Can Modify Lipopolysaccharide O-Antigens Synthesized by an ATP-binding Cassette (ABC) Transporter-dependent Assembly Mechanism

“…In many Gramnegative bacteria, the O-antigen is a critical determinant in resistance to serum killing (44). Although glucosylation does not appear to change this role in Salmonella and Shigella (43,45,46), other cellular properties are certainly impacted in a species-specific manner. In Shigella, glucosylation leads to greater invasion, which is correlated to enhanced function and exposure of the type 3 secretion system (43), and elevated acid tolerance (47).…”

“…In Shigella, glucosylation leads to greater invasion, which is correlated to enhanced function and exposure of the type 3 secretion system (43), and elevated acid tolerance (47). In Salmonella, glucosylation is associated with virulent isolates (48) but is not a stable property leading to antigenic (form) variation in the O serotype (45,46,49). Glucosylation is induced by exposure to macrophages, and although not required for invasion and systemic spread, it appears to enhance long term colonization (46).…”

“…In Salmonella, glucosylation is associated with virulent isolates (48) but is not a stable property leading to antigenic (form) variation in the O serotype (45,46,49). Glucosylation is induced by exposure to macrophages, and although not required for invasion and systemic spread, it appears to enhance long term colonization (46).…”