TY - JOUR
T1 - Research in a time of enteroids and organoids
T2 - how the human gut model has transformed the study of enteric bacterial pathogens
AU - Ranganathan, Sridevi
AU - Smith, Emily M.
AU - Foulke-Abel, Jennifer D.
AU - Barry, Eileen M.
N1 - Funding Information:
National Institute of Allergy and Infectious Diseases [U19 AI142725]; National Institute of Allergy and Infectious Diseases [P01 AI125181]; National Institute of Allergy and Infectious Diseases [U19 AI109776]; National Institute of Diabetes and Digestive and Kidney Diseases [K01 DK113043]; National Institute of Diabetes and Digestive and Kidney Diseases [P30 DK089502].
Publisher Copyright:
© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.
PY - 2020/11/9
Y1 - 2020/11/9
N2 - Enteric bacterial pathogens cause significant morbidity and mortality globally. Studies in tissue culture and animal models shaped our initial understanding of these host–pathogen interactions. However, intrinsic shortcomings in these models limit their application, especially in translational applications like drug screening and vaccine development. Human intestinal enteroid and organoid models overcome some limitations of existing models and advance the study of enteric pathogens. In this review, we detail the use of human enteroids and organoids to investigate the pathogenesis of invasive bacteria Shigella, Listeria, and Salmonella, and noninvasive bacteria pathogenic Escherichia coli, Clostridium difficile, and Vibrio cholerae. We highlight how these studies confirm previously identified mechanisms and, importantly, reveal novel ones. We also discuss the challenges for model advancement, including platform engineering to integrate environmental conditions, innate immune cells and the resident microbiome, and the potential for pre-clinical testing of recently developed antimicrobial drugs and vaccines.
AB - Enteric bacterial pathogens cause significant morbidity and mortality globally. Studies in tissue culture and animal models shaped our initial understanding of these host–pathogen interactions. However, intrinsic shortcomings in these models limit their application, especially in translational applications like drug screening and vaccine development. Human intestinal enteroid and organoid models overcome some limitations of existing models and advance the study of enteric pathogens. In this review, we detail the use of human enteroids and organoids to investigate the pathogenesis of invasive bacteria Shigella, Listeria, and Salmonella, and noninvasive bacteria pathogenic Escherichia coli, Clostridium difficile, and Vibrio cholerae. We highlight how these studies confirm previously identified mechanisms and, importantly, reveal novel ones. We also discuss the challenges for model advancement, including platform engineering to integrate environmental conditions, innate immune cells and the resident microbiome, and the potential for pre-clinical testing of recently developed antimicrobial drugs and vaccines.
KW - Human intestinal enteroids
KW - bacterial pathogens
KW - enteric bacteria
KW - organoids
UR - http://www.scopus.com/inward/record.url?scp=85089477437&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85089477437&partnerID=8YFLogxK
U2 - 10.1080/19490976.2020.1795389
DO - 10.1080/19490976.2020.1795389
M3 - Review article
C2 - 32795243
AN - SCOPUS:85089477437
SN - 1949-0976
VL - 12
JO - Gut Microbes
JF - Gut Microbes
IS - 1
M1 - 1795492
ER -