Enteropathogenic Infections: Organoids Go Bacterial

Table 1

Causative agent	Source and characteristics of infected organoid culture system	Findings/ objectives	References
Campylobacter jejuni	(i) Adult murine small intestinal organoids	(i) Infection-related genotoxicity (induction of DNA strand breaks)	(i) [86]
Clostridium difficile	(i) iPSC-derived human intestinal organoids; (ii) iPSC-derived human intestinal organoids	(i) Attenuation of Cdt B-induced cytopathic effect by exposure to HSA; (ii) Neutralization of TcdB-induced cytoskeletal disarray by bacitracin	(i) [83]; (ii) [84]
Enterohemorrhagic Escherichia coli	(i)Adult human colon-derived organoids; (ii) ESC-derived human intestinal organoids supplemented with PMN	(i) EspP-mediated proteolytic degradation of protocadherin 24, effacement of microvillar bridges of the enterocytic brush border; EspP equipped with enterotoxin-like properties; (ii) In vitro modeling of EHEC enteric invasive infection	(i) [44]; (ii) [49]
Enterotoxinogenic Escherichia coli	(i) Adult human small intestinal organoids; (ii) Adult human small intestinal organoids supplemented with monocyte-derived macrophages	(i) Preferential adhesion to blood group A-glycosylated epithelial surfaces via lectin EtpA; (ii) Mitigation of bacteria-stimulated inflammation and intestinal barrier dysfunction by resident macrophages	(i) [30]; (ii) [31]
Listeria monocytogenes	(i) Fetal tissue-derived human intestinal organoids; (ii)Adult human small intestinal “basal-out” organoids; (iii) Adult murine intestinal organoids	(i) Goblet cells as preferred cell type of entry; (ii) Enforced endocytotic uptake via basolateral cellular target structures E-cadherin and Met; (iii) Accelerated epithelial renewal and reduction in goblet cell numbers mediated by STAT1 and STAT3	(i) [67]; (ii) [59]; (iii) [72]
Salmonella spcc.	(i) Adult human small intestinal organoids; (ii) Adult murine small intestinal “apical-out” organoids; (iii) Adult human ileum-derived organoids; (iv) Adult murine small intestinal organoids; (v) Adult murine small intestinal organoids supplemented with probiotic L. acidophilus	(i) Inducible transdifferentiation of enterocytes into M cells as favored portal of entry; (ii) Preference of apical transmission route; luminal shedding of infected enterocytes; (iii) Invasion and intracellular dispersion dependent on exploitation of host cell cytoskeleton; (iv) Disintegration of epithelial Zonula occludens, enhanced NF-κB signaling; upregulation of goblet cell gene markers; (v) Reversal of infection-induced upregulation of Wnt3 and Toll-like receptor 2 and 4	(i) [54]; (ii) [59]; (iii) [60]; (iv) [61, 62]; (v) [63]
Shigella flexneri	(i) Adult human colon-derived organoids; (ii) Adult human ileum-derived organoids pretreated with TNF α to amplify M cell population; (iii) Adult human colon-derived organoids; (iv) Adult human intestinal organoids	(i) Production of adhesive biofilm dependent on luminal exposure to glucose and bile salts; (ii) Preferred host cell invasion via M cell transcytosis, enhanced NF-κB signaling; upregulation of MUC2 expression; (iii) Polymerization of actin fibers to facilitate intracellular trafficking; enhanced NF-κB signaling; (iv) Anti-infective effectiveness of bacteriophages	(i) [37]; (ii) [38]; (iii) [39]; (iv) [41]
Vibrio cholerae	(i) Swelling assay conducted in human adult rectum-derived organoids; (ii) iPSC-derived human intestinal organoids	(i) Neutralization of CT by monovalent and multivalent metanitrophenyl α-galactoside-bound polymers; (ii) In vitro modeling of cholera enteric infection	(i) [21]; (ii) [23]