Mechanisms for Lactobacillus rhamnosus treatment of intestinal infection by drug-resistant Escherichia coli.

Abstract

The development of probiotics as therapeutic drugs is greatly important for the protection against threats of drug-resistant pathogen infection in both humans and animals. This study showed that Lactobacillus rhamnosus SHA113, previously isolated from breast milk of healthy humans, showed efficient therapeutic effects on infection by drug resistant Escherichia coli QBQ009. In addition to protecting the intestinal barrier via up-regulating the expression of tight junction proteins ZO-1 and occludin, it was also found that (1) both L. rhamnosus SHA113 and E. coli QBQ009 cells caused changes of the epithelial cell cytoskeleton and up-regulated the expression of phagocytosis-related proteins MYH2 in Caco-2 cells; however, only E. coli QBQ009 caused a strong decrease of cell viability. L. rhamnosus SHA113 treatment after E. coli QBQ009 infection significantly restored the damaged intestinal barrier and the changes of the epithelial cell cytoskeleton caused by E. coli QBQ009. (2) L. rhamnosus SHA113 showed a much higher adhesion rate to the intestinal tract and Caco-2 cells than E. coli QBQ009. The presence of E. coli QBQ009 significantly decreased the adhesion rate of L. rhamnosus SHA113, but not in reverse. (3) L. rhamnosus SHA113 had much higher self-coagulation than E. coli, and could strongly co-coagulate with E. coli QBQ009. The viability of E. coli QBQ009 greatly decreased after co-coagulation, while that of L. rhamnosus SHA113 was not influenced. (4) The polysaccharides produced by L. rhamnosus SHA113 significantly decreased the permeability of the intestinal tract and Caco2 cells, but had no remarkable influence on the adhesion rate of E. coli QBQ009. (5) Feeding L. rhamnosus SHA113 caused a significant reduction of Proteobacteria in the cecum of healthy mice, which was not significant in infected and treated mice. In summary, the decreased live pathogen amounts might be one of the decisive factors for the efficient cure of E. coli QBQ009 infection by L. rhamnosus SHA113, and the restoration of the intestinal barrier might be caused by the reduction of pathogens.