Organoid and Enteroid Modeling of Salmonella Infection

Salmonella are Gram-negative rod-shaped facultative anaerobic bacteria that are comprised of over 2,000 serovars. They cause gastroenteritis (salmonellosis) with headache, abdominal pain and diarrhea clinical symptoms. Salmonellosis brings a heavy burden for the public health in both developing and developed countries. Antibiotics are usually effective in treating the infected patients with severe gastroenteritis, although antibiotic resistance is on the rise. Understanding the molecular mechanisms of Salmonella infection is vital to combat the disease. In vitro immortalized 2-D cell lines, ex vivo tissues/organs and several animal models have been successfully utilized to study Salmonella infections. Although these infection models have contributed to uncovering the molecular virulence mechanisms, some intrinsic shortcomings have limited their wider applications. Notably, cell lines only contain a single cell type, which cannot reproduce some of the hallmarks of natural infections. While ex vivo tissues/organs alleviate some of these concerns, they are more difficult to maintain, in particular for long term experiments. In addition, non-human animal models are known to reflect only part of the human disease process. Enteroids and induced intestinal organoids are emerging as effective infection models due to their closeness in mimicking the infected tissues/organs. Induced intestinal organoids are derived from iPSCs and contain mesenchymal cells whereas enteroids are derive from intestinal stem cells and are comprised of epithelial cells only. Both enteroids and induced intestinal organoids mimic the villus and crypt domains comparable to the architectures of the in vivo intestine. We review here that enteroids and induced intestinal organoids are emerging as desired infection models to study bacterial-host interactions of Salmonella.