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Cell Host Microbe ; 29(9): 1351-1365.e11, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34403684

RESUMO

Bacterial ADP-ribosyltransferases (ADPRTs) have been described as toxins involved in pathogenesis through the modification of host proteins. Here, we report that ADPRTs are not pathogen restricted but widely prevalent in the human gut microbiome and often associated with phage elements. We validated their biochemical activity in a large clinical isolate collection and further examined Bxa, a highly abundant ADPRT in Bacteroides. Bxa is expressed, secreted, and enzymatically active in Bacteroides and can ADP-ribosylate non-muscle myosin II proteins. Addition of Bxa to epithelial cells remodeled the actin cytoskeleton and induced secretion of inosine. Bxa-encoding B. stercoris can use inosine as a carbon source and colonizes the gut to significantly greater numbers than a bxa-deleted strain in germ-free and altered Schaedler flora (ASF) mice. Colonization correlated with increased inosine concentrations in the feces and tissues. Altogether, our results show that ADPRTs are abundant in the microbiome and act as bacterial fitness factors.


Assuntos
ADP Ribose Transferases/metabolismo , Citoesqueleto de Actina/metabolismo , Bacteroides thetaiotaomicron/metabolismo , Bacteroides/metabolismo , Células Epiteliais/metabolismo , Inosina/metabolismo , ADP Ribose Transferases/genética , Animais , Bacteriófagos/genética , Células CACO-2 , Linhagem Celular Tumoral , Fezes/química , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Vida Livre de Germes , Células HT29 , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Cadeias Pesadas de Miosina/metabolismo
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