Review Article

Enteropathogenic Infections: Organoids Go Bacterial

Table 1


Causative agentSource and characteristics of infected organoid culture systemFindings/ objectivesReferences

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]