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  • Gut metabolite L-lactate supports Campylobacter jejuni population expansion during acute infection [Elektronski vir]
    Sinha, Ritam ...
    How the microaerobic pathogen Campylobacter jejuni establishes its niche and expands in the gut lumen during infection is poorly understood. Using 6-wk-old ferrets as a natural disease model, we ... examined this aspect of C. jejuni pathogenicity. Unlike mice, which require significant genetic or physiological manipulation to become colonized with C. jejuni, ferrets are readily infected without the need to disarm the immune system or alter the gut microbiota. Disease after C. jejuni infection in ferrets reflects closely how human C. jejuni infection proceeds. Rapid growth of C. jejuni and associated intestinal inflammation was observed within 2 to 3 d of infection. We observed pathophysiological changes that were noted by cryptic hyperplasia through the induction of tissue repair systems, accumulation of undifferentiated amplifying cells on the colon surface, and instability of HIF-1α in colonocytes, which indicated increased epithelial oxygenation. Metabolomic analysis demonstrated that lactate levels in colon content were elevated in infected animals. A C. jejuni mutant lacking lctP, which encodes an L-lactate transporter, was significantly decreased for colonization during infection. Lactate also influences adhesion and invasion by C. jejuni to a colon carcinoma cell line (HCT116). The oxygenation required for expression of lactate transporter (lctP) led to identification of a putative thiol-based redox switch regulator (LctR) that may repress lctP transcription under anaerobic conditions. Our work provides better insights into the pathogenicity of C. jejuni.
    Source: Proceedings of the National Academy of Sciences of the United States of America [Elektronski vir]. - ISSN 1091-6490 (Vol. 121, iss. 2, [article no.] e2316540120, Jan. 3, 2024, str.)
    Type of material - e-article ; adult, serious
    Publish date - 2024
    Language - english
    COBISS.SI-ID - 179511555

    Link(s):

    https://www.pnas.org/doi/10.1073/pnas.2316540120
    DOI

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