AUTHOR=Shaw Claire , Weimer Bart C. , Gann Reed , Desai Prerak T. , Shah Jigna D. 

TITLE=The Yin and Yang of pathogens and probiotics: interplay between Salmonella enterica sv. Typhimurium and Bifidobacterium infantis during co-infection

JOURNAL=Frontiers in Microbiology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2024.1387498

DOI=10.3389/fmicb.2024.1387498

ISSN=1664-302X

ABSTRACT=<p>Probiotic bacteria have been proposed as an alternative to antibiotics for the control of antimicrobial resistant enteric pathogens. The mechanistic details of this approach remain unclear, in part because pathogen reduction appears to be both strain and ecology dependent. Here we tested the ability of five probiotic strains, including some from common probiotic genera <italic>Lactobacillus</italic> and <italic>Bifidobacterium</italic>, to reduce binding of <italic>Salmonella enterica</italic> sv. Typhimurium to epithelial cells <italic>in vitro. Bifidobacterium longum</italic> subsp. <italic>infantis</italic> emerged as a promising strain; however, <italic>S.</italic> Typhimurium infection outcome in epithelial cells was dependent on inoculation order, with <italic>B. infantis</italic> unable to rescue host cells from preceding or concurrent infection. We further investigated the complex mechanisms underlying this interaction between <italic>B. infantis</italic>, <italic>S.</italic> Typhimurium, and epithelial cells using a multi-omics approach that included gene expression and altered metabolism via metabolomics. Incubation with <italic>B. infantis</italic> repressed apoptotic pathways and induced anti-inflammatory cascades in epithelial cells. In contrast, co-incubation with <italic>B. infantis</italic> increased in <italic>S.</italic> Typhimurium the expression of virulence factors, induced anaerobic metabolism, and repressed components of arginine metabolism as well as altering the metabolic profile. Concurrent application of the probiotic and pathogen notably generated metabolic profiles more similar to that of the probiotic alone than to the pathogen, indicating a central role for metabolism in modulating probiotic-pathogen-host interactions. Together these data imply crosstalk via small molecules between the epithelial cells, pathogen and probiotic that consistently demonstrated unique molecular mechanisms specific probiotic/pathogen the individual associations.</p>