摘要Intestinal drug-resistant pathogens,e.g.,Salmonella enterica subsp.enterica serovar Typhimurium(S.Tm)and enteropathogenic Escherichia coli(E.coli),frequently cause life-threatening infectious enteritis.Probiotic-based therapy is a promising way to eliminate drug-resistant pathogens for treatment of infectious enteritis,but its colonizing and therapeutic efficacy after oral administration are limited.Here,we developed a facile therapeutic agent to treat infectious enteritis by co-assembly of the peptide nanodrug melittin-loaded MSN grafted by polysaccharide-binding protein(MMPB)with the famous probiotic bacteria Lactobacillus plantarum(Lac)and Bifidobacterium animalis subsp.lactis(Bif).The nanodrug was composed of the antimicrobial peptide melittin and mesoporous silica nanoparticles exposing the artificial polysaccharide-binding protein.Owing to presence of the artificial protein on the MMPB surface,the nanodrug strongly bound and cross-linked the probiotic cells,forming the Lac+Bif+MMPB co-assembly.During co-incubation with the kanamycin-resistant E.coli strain(Ecka),the co-assembly strongly reduced the viability of Ecka,leading to the increase in the ratio of probiotic to Ecka from 1.6 to 9.2.After oral administration of the co-assembly to the mice pre-colonized by Ecka,Lac+Bif+MMPB almost eliminated the kanamycin-resistant gene in the intestine,and led to 2-3-fold higher levels of the probiotic cells than the nanodrug MMPB or the combined probiotics Lac+Bif.More importantly,in the mice suffering from enteritis caused by drug-resistant S.Tm,the co-assembly remarkably recovered the mouse body weight,reduced intestine colonization of S.Tm cells,and decreased the levels of pro-inflammatory cytokines in both serum and colons.This study realized the synthetic biology technique-mediated abiotic/biotic co-assembly for efficient treating infectious enteritis induced by drug-resistant pathogens.