Deletion of major shell proteins of ethanolamine utilization microcompartment reduces intrinsic antibiotic resistance, biofilm and intracellular survival of Salmonella Typhimurium

With the high rise in Salmonella infection and emergence of antibiotic resistant variants, it is imperative to develop novel strategy to control pathogen. Earlier study revealed that Salmonella deploys ethanolamine (EA) metabolic machinery to disseminate in the intestine. Salmonella with defective in EA metabolism is manifested with lower intestinal colonization efficiency. Remarkably, potential of EA metabolism as therapeutic target is yet to explore. Our study revealed that supplementation of EA and vitamin B₁₂ in both rich and minimal media enhanced biofilm formation, increased motility and increased tolerance of Salmonella to some antibiotics. Conversely, mutants deficient in EA metabolic enzymes did not exhibit any physiological fitness. In Salmonella, EA metabolic enzymes are localized within a proteinaceous microcompartment (MCP) shell composed of thousands copies of shell proteins encoded by five genes from eut operon. Intriguingly, bacterial cells with defective MCP shell due to mutation in individual shell protein showed enhanced susceptibility towards a number of antibiotics in minimal media. The shell protein mutants were unable to form biofilms, produced lower curli expression and were defective in flagellar motility. The shell protein mutant also exhibited lower intramacrophagic viability. Notably, phenotypes were restored upon ectopic expression of corresponding genes. It was evident that mutation in the MCP shell protein downregulated the expression of genes related pathogenicity. Overall, this study sheds new light on understanding the relationship between EA metabolism and bacterial physiology that would pave the way of developing novel therapeutic interventions against Salmonella.