Nature
Researchers led by the University of Illinois Chicago showed that Candida albicans, a common yeast in the intestinal microbiota, facilitates the colonization of Salmonella Typhimurium and its spread to distant organs. The Salmonella protein SopB induces the yeast to produce and secrete arginine, which activates the bacterium’s virulence traits while reducing the host’s inflammatory signalling.
Microbial communities in the gut influence human health through mechanisms such as colonization resistance, immune education, digestion and systemic signalling. Bacterial species receive most research focus, whereas the contributions of viruses and fungi remain under‑explored.
Changes in the gut mycobiome have been linked to several gastrointestinal disorders, but how fungi interact with resident bacteria during infection is largely unknown.
Non‑typhoidal Salmonella is a well‑studied enteric pathogen, infecting roughly 100 million people annually. In healthy hosts the disease is usually limited to the gut, producing inflammatory diarrhoea, whereas immunocompromised individuals risk bacterial dissemination to extra‑intestinal sites.
Successful gut colonisation requires out‑competing native microorganisms. While commensal fungi are present across mammalian species, their roles during enteric disease remain poorly defined.
Candida albicans colonises many human mucosal surfaces, appearing in the gut of more than 60 % of healthy adults. Although typically a harmless commensal, it can become pathogenic, particularly in immunosuppressed individuals. A key virulence feature is its ability to switch from yeast to hyphal forms that penetrate epithelial layers.
Links between C. albicans and inflammatory bowel disease, especially Crohn’s disease, have been reported. While the yeast alone does not trigger gut inflammation, it can exacerbate pre‑existing inflammatory conditions. Both Salmonella and C. albicans thrive under inflammatory gut environments, suggesting that patients harbouring the yeast may encounter Salmonella infection with greater susceptibility.
The study, titled Commensal yeast promotes Salmonella Typhimurium virulence and published in Nature, examined cross‑kingdom interactions to determine how Candida influences Salmonella colonisation, systemic spread and host inflammatory responses.
Nature
Mouse cohorts included C57BL/6 and CBA/J strains that received either a streptomycin primer or no antibiotics, and additional models comprised germ‑free mice or animals carrying an eight‑member altered Schaedler flora (ASF). In vitro experiments used human colonic epithelial lines T84 and Caco‑2.
Nature
Two experimental designs were used in mice: one in which animals received antibiotics followed by infection, and a second in which mice were first colonised with Candida albicans without antibiotic treatment. Salmonella was inoculated at a 10:1 ratio to yeast, and samples were collected at 24, 48 and 72 hours to assess bacterial loads in the gut, spleen and liver, as well as weight loss. Some groups received 2 % L‑arginine in drinking water (pH 7) or 20 mM L‑lysine.
In vitro, T84 and Caco‑2 cells were exposed to Salmonella (multiplicity of infection 1) for two hours, alone or together with live Candida at the same 10:1 ratio. Heat‑killed Candida and the β‑glucan curdlan served as controls. Microbial adhesion was measured by sedimentation and microscopy, and the addition of mannose reduced binding.
Genetic mutants of Salmonella lacking components essential for adhesion or secretion, as well as an arginine transporter, were tested. Candida strains deficient in arginine biosynthesis were also generated, with a revertant restored for this pathway.
Readouts included RNA sequencing with pathway analysis, rt‑qPCR for invasion and arginine‑related genes, single‑cell SPI‑1 reporters, metabolomic profiling of amino acids in supernatants and mouse gut contents, tests of co‑culture supernatant on invasion, 16S and ITS sequencing of microbiota, and host analyses such as gene expression, serum cytokines, neutrophil infiltration and histopathology scoring.
Presence of Candida in the gut led to higher Salmonella numbers in the large intestine and increased bacterial translocation to spleen and liver, with co‑infected mice displaying greater weight loss. Candida also promoted Salmonella uptake in human colonic cells. Gene expression data revealed that Salmonella’s invasion system was up‑regulated near yeast.
Co‑cultures contained millimolar concentrations of arginine, and adding L‑arginine alone boosted invasion in a dose‑dependent fashion. A Salmonella mutant lacking the arginine transporter did not respond to Candida. Candida mutants that could not produce arginine failed to enhance Salmonella invasion or gut colonisation; restoring the arginine pathway rescued this effect.
SopB activated Candida’s arginine‑biosynthetic genes, leading to arginine release, and deletion of sopB abolished the observed influence.
Co‑infected mice exhibited dampened inflammatory signals, including reduced Il17, Cxcl1, serum IFNγ and neutrophil influx. Supplementation with 2 % L‑arginine in drinking water mimicked this attenuation and increased systemic spread, whereas L‑lysine partially reversed Candida‑driven alterations.
The authors conclude that Candida albicans colonisation constitutes a risk factor for Salmonella infection, with arginine acting as a key metabolite linking fungal, bacterial and host pathways. These findings highlight SopB‑mediated arginine production in the yeast as a determinant that stimulates Salmonella invasion while softening host inflammatory responses.
Evidence for Candida presence in patients with Salmonella Typhimurium infection remains limited. A referenced report from Cameroon noted a four‑fold rise in recurrent typhoid or paratyphoid cases among individuals colonised with Candida. The authors suggest that antifungal therapy might be a potential strategy for vulnerable populations.
Written for you by our author Justin Jackson, edited by Sadie Harley, and fact‑checked and reviewed by Robert Egan—this article is a product of careful human work. We rely on readers like you to keep independent science journalism alive. If you care about this reporting, please consider a donation (especially monthly). You’ll receive an ad‑free account as a thank‑you.
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