The addition of glycerol to Lactobacillus reuteri converted it into the antimicrobial compound reuterin, which preferentially targeted the pathogenic Clostridium difficile, found the research team from Baylor College of Medicine (BCM), Houston.
The L. reuteri-derived reuterin killed C. difficile, often described as a superbug, without affecting the 'good' bacteria when tested in a mini-bioreactor model. The effect was strain-specific and the reuterin was as effective in inhibiting C. difficile growth as the conventional antibiotic vancomycin.
“Using the mini-bioreactors model we showed that L. reuteri reduced the burden of C. difficile infection in a complex gut community,” commented Professor Robert Britton from BCM. “To achieve its beneficial effect, L. reuteri requires glycerol and converts it into the antimicrobial reuterin.”
Reuterin is generally known as a broad-spectrum antibiotic; it affects the growth of a wide variety of bacteria when they are tested individually in the lab.
However, to the surprise of researchers, reuterin did not have this effect in the mini-bioreactor where multiple bacterial species were present. Thus beneficial bacteria were left unharmed, unlike when conventional antibiotics are used to treat C. difficile.
“I expected reuterin to have an antibacterial effect on several different types of bacteria in the community, but it only affected C. difficile and not the good bacteria, which was exciting because it has major implications for a preventative strategy,” said first author Dr. Jennifer Spinler.
Significance
The findings are significant because they may enable prophylactic treatment with probiotics before taking antibiotics, which are known to disrupt ‘good’ bacteria in the gut.
Co-administering the L.reuteri / glycerol would maintain the beneficial species, while preventing the growth of C. difficile. If effective, any future treatment could have multiple benefits including shorter hospital stays, fewer cases of antibiotic induced diarrhoea and lower incidence of recurrent C.difficile infections.
The use of next-generation probiotics such as L.reuteri might also prove to bea new weapon in the fight against antibiotic resistance.
Strain-specific effect
The reuterin production capability of L. reuteri is strain-specific and is dependent upon an active pocR gene (responsible for regulating cobalmin synthesis and propanediol degradation).
The researchers identified two notable bacterial strains capable of producing reuterin in the presence of glycerol: L. reuteri 17938 and6475. Strain 17938 produced three times as much reuterin as 6475.
Previous studies had established that the parent strain of L. reuteri 17938 was instrinically resistant to several antibiotics including vancomycin and metronidazole. In order to comply with recommendations from the EU PROSAFE Project that probiotic strains should not possess antibiotic resistance traits, earlier experiments by other researchers removed the genes responsible for antibiotic resistance, resulting in the daughter strain 17938.
The future
“Although these results are too preliminary to be translated directly into human therapy, they provide a foundation upon which to further develop treatments,” said co-author Dr. Jennifer Auchtung.
Human studies are currently in progress to determine whether co-administration of L. reuteri and glycerol can be used to treat the ‘superbug’ in vivo. The researchers are optimistic that the treatment could prove to be “a front-runner for next-generation probiotics as adjunct therapy in C. difficile infection prevention”.
Source: Infection and Immunity
Volume 85, issue 8. Published online ahead of print. doi: 10.1128/IAI.00303-17
“Next-generation probiotics targeting Clostridium difficile through precursor-directed antimicrobial biosynthesis”
Authors: Jennifer K Spinler, Jennifer Auchtung, Robert A. Britton et al