A novel bacteriocin produced by Bifidobacterium longum subsp. infantis has dual antimicrobial and immunomodulatory activity

Abstract

Bacteriocins are ribosomally-synthesized antimicrobial peptides produced by bacteria with either narrow or broad spectrum activity. Many genome mining studies have indicated that bacteriocin gene clusters are widespread within certain gut microbiota members. In early life, Bifidobacterium comprise the dominant microbiota genus in vaginally delivered and breast-fed infants, with high levels associated with improved health. However, in many cases the mechanisms underlying these beneficial effects are unknown, although a limited number of studies have suggested that bacteriocin production by Bifidobacterium may represent a key mechanism for preventing pathogen over-growth. Here, we used BAGEL4 and antiSMASH to identify putative bacteriocin sequences in the whole genome sequences of 33 Bifidobacterium strains isolated from infants participating in two clinical studies. We identified a novel non-lantibiotic bacteriocin from Bifidobacterium longum subsp. infantis LH_664, with 40% sequence homology to Lactococcin 972 from Lactococcus lactis subsp. lactis. The putative bacteriocin (Bifidococcin_664) was chemically synthesized and studied for antimicrobial and immune-modulatory activities. We determined it has discrete activity against Clostridium perfringens and it appears to have novel immune stimulatory activities, promoting macrophage phagocytosis and specific cytokine release. These data highlight strain-specific beneficial properties in the early life genus Bifidobacterium, and suggest avenues for development of novel and highly specific dual action antimicrobials, and possible probiotic strains, that are active against clinically important bacterial pathogens.

Microbiome-liver crosstalk: A multihit therapeutic target for liver disease

“…Colonization resistance is also aided by the production of toxic antimicrobial peptides by commensals. For example, many members of the phylum Bacteroidetes produce toxic antimicrobial peptides through their type 6 secretion systems (T6SS)[ 16 ], E. coli produces narrow-spectrum antibiotics called microcins that effectively kill competitors within their niche[ 17 , 18 ], and the probiotic Bifidobacterium secretes broad-spectrum bacteriocins[ 19 ].…”