講演要旨

The mechanisms that allow enteric pathogens to colonize the intestine in the presence of the microbiota and how host immunity and the indigenous microbiota inhibit pathogen colonization remain poorly understood. Our laboratory is using Citrobacter rodentium, a mouse pathogen that models human infections by enteropathogenic E. coli, to understand the mechanisms that regulate the colonization and clearance of the pathogen in the gut. These studies have revealed how the pathogen colonizes and replicates successfully early during infection and how host immunity and the indigenous microbiota cooperate to eradicate the pathogen in the later stage of the infection. These studies have also revealed that Clostridia species protect the host from colonization by C. rodentium and Salmonella enterica in the intestine. Furthermore, these studies have shown that the intestine of mice after birth lack protective Clostridia providing a mechanism to account for the enhanced susceptibility of mice and humans to enteric infection during the neonatal period.

References:
1. Kamada, N., Kim, Y.G., Sham, H.P., Vallance, B.A., Puente, J.L., Martens, E.C., Núñez, G. (2012). Regulated virulence controls the ability of a pathogen to compete with the gut microbiota. Science 6086: 1325-1329.
2. Kamada, N., Sakamoto, K., Seo, S.U., Zeng, M.Y., Kim, Y.G., Cascalho, M., Vallance, B.A., Puente, J.L., Núñez, G. (2015). Humoral Immunity in the Gut Selectively Targets Phenotypically Virulent Attaching-and-Effacing Bacteria for Intraluminal Elimination. Cell Host & Microbe. 17:617-27.
3. Kim Y-G, Sakamoto K, Seo S-U, Pickard JM, Gillilland MG III, Pudlo NA, Hoostal M, Li X, Wang TD, Feehley T, Stefka AT, Schmidt TM, Martens EC, Fukuda S, Inohara N, Nagler CR, Núñez G. (2017). Neonatal Acquisition of Clostridia Species Protects Against Colonization by Bacterial Pathogens. Science 356:315-319