Escherichia coli GutM4 produces 2,5-diketopiperazines and inhibits human pathogens in vitro

Abstract

Background: It has been a very common practice to use probiotics or their metabolites as alternative antimicrobial strategies for treatment and prevention of infections, since the rampant and indiscriminate use of antibiotics causes the development of antibiotic resistant pathogens. The objective of this study is to select a potential antimicrobial probiotic of Escherichia coli strain from human gastrointestinal tract, and investigate the production of diketopiperazines that contribute to the antimicrobial activity.

Results: From feces of a health adult, E. coli GutM4 was isolated. E. coli GutM4 showed significant antagonistic activity to all the ten indicating pathogens, and no less than that of reference strain E. coli Nissle 1917 against to eight of the ten indicating pathogens. Moreover, E. coli GutM4 produced antagonistic substances with trypsin-targeted peptide bonds, because the inhibitory effects of E. coli GutM4 supernatant treated with trypsin significantly decreased. Consistent with antagonistic activity and peptide compounds of E. coli GutM4, fourteen 2,5-diketopiperazines were isolated from fermented broth of E. coli GutM4, including 12 Cyclo(Pro-Phe), 3 cyclo(Pro-Tyr), and 5 cyclo(4-hydroxyl-Pro-Ieu), which are reported with determined anti-pathogen activity.

Conclusion: E. coli GutM4 produce 2,5-diketopiperazines that partly involve in the antagonistic action against human pathogens in vitro