Salmonella enterica serovar Typhimurium chitinases modulate the intestinal glycome and promote small intestinal invasion

Abstract

Salmonella enterica serovar Typhimurium ( Salmonella ) is one of the leading causes of food-borne illnesses worldwide. To colonize the gastrointestinal tract, Salmonella produces multiple virulence factors that facilitate cellular invasion. Chitinases have been recently emerging as virulence factors for various pathogenic bacterial species and the Salmonella genome contains two annotated chitinases: STM0018 ( chiA ) and STM0233. However, the role of these chitinases during Salmonella pathogenesis is unknown. The putative chitinase STM0233 has not been studied previously and only limited data exists on ChiA. Chitinases typically hydrolyze chitin polymers, which are absent in vertebrates. However, chiA expression was detected in infection models and purified ChiA cleaved carbohydrate subunits present on mammalian surface glycoproteins, indicating a role during pathogenesis. Here, we demonstrate that expression of chiA and STM0233 is upregulated in the mouse gut and that both chitinases facilitate epithelial cell adhesion and invasion. Salmonella lacking both chitinases showed a 70% reduction in invasion of small intestinal epithelial cells in vitro. In a gastroenteritis mouse model, chitinasedeficient Salmonella strains were also significantly attenuated in the invasion of small intestinal tissue. This reduced invasion resulted in significantly delayed Salmonella dissemination to the spleen and the liver, but chitinases were not required for systemic survival. The invasion defect of the chitinase-deficient strain was rescued by the presence of wild-type Salmonella , suggesting that chitinases are secreted. By analyzing N -linked glycans of small intestinal cells, we identified specific N -acetylglucosamine-containing glycans as potential extracellular targets of Salmonella chitinases. This analysis also revealed differential abundance of Lewis X-containing glycans that is likely a result of host cell modulation due to the detection of Salmonella chitinases. Similar glycomic changes elicited by chitinase deficient strains indicate functional redundancy of the chitinases. Overall, our results demonstrate that Salmonella chitinases contribute to intestinal adhesion and invasion through modulation of the host glycome.

Genes associated with fitness and disease severity in the pan-genome of mastitis-associatedEscherichia coli

“…Alternatively, it is possible that ChiA contributes to infection through glycosidase activity, independently of its binding to host proteins. Salmonella chitinases modify glycans present in the extracellular matrix, uncovering mannose residues present on the epithelial surface and making them available for attachment through type I fimbriae (94,95). They also increase survival inside phagocytes by dampening the expression of host antimicrobial responses in dendritic cells and macrophages (94).…”

Multi-omics reveal Salmonella-liberated dietary L-arabinose promotes expansion in superspreaders

“…Interestingly, chitinases, which hydrolyze chitin polymers into N-acetyl glucosamine oligomers, are a well-studied family of glycoside hydrolases in pathogens. Recent work has characterized Salmonella’s GH18 family chitinases and have shown them to be important for epithelial adhesion and invasion (Devlin et al ., 2021; Chandra et al ., 2022). Chitinases have been identified as important virulence factors for several other pathogenic bacterial species including Legionella pneumophila (Rehman et al ., 2020), Listeria monocytogenes (Chaudhuri et al ., 2013), Vibrio cholerae (Mondal et al ., 2014), and Adherent-invasive Escherichia coli (Low et al ., 2013).…”

Human gut metagenomes encode diverse GH156 sialidases

“…We therefore filtered our data to remove hits with less than 275 bp of coverage in each sample. The two remaining non-UHGP-95 genes detected in at least one sample included PWL98936.1 from Mann et al, 15 Uniprot and GEM-PF_16266 from GEM, which are both derived from human fecal metagenomes, providing strong support that all hits included in the analyses are truly present in the sample.…”

“…Collectively, N-and O-glycans on host proteins play myriad roles, notably in cell-to-cell signalling, host-microbe interactions and immune system regulation (11) and the enzymes that contribute to their destruction are recognized virulence factors (12)(13)(14)(15). The colonic epithelium is protected from direct assault by a glycocalyx overlaid by a carbohydrate-rich mucous bilayer embedded with antimicrobial proteins (16).…”