Biology subjects

Todd, O. A.

Publications and source records attributed to Todd, O. A..

4 recordsLinked to original sources

bioRxiv2026

Fiber Formulation-Dependent Modulation of Gut Microbial Metabolism in Parkinsons Disease

Parkinsons disease (PD) is associated with altered gut-brain signaling, including microbial dysbiosis, intestinal inflammation, and reduced short-chain fatty acid (SCFA) production. Because dietary fibers are selectively fermented by intestinal microbes to generate SCFAs, fiber formulations tailored to the altered intestinal environment in PD offer a strategy to modulate microbial dysfunction. Here, we used the ex vivo Systemic Intestinal Fermentation Research (SIFR(R)) technology platform, which enables assessment of gut microbiome modulation and host-relevant readouts with demonstrated translational relevance, to assess how fiber substrates influence microbial composition and metabolism of fecal microbiota from individuals with PD (n = 6). Fecal samples were incubated for 24 h with single-fiber, multi-fiber, and food-based formulations. Fermentation outputs, including pH, gas, and SCFAs, were quantified, and select formulations were further characterized by profiling microbial community structure and metabolite output. Relative to a parallel untreated control and osmotic laxative comparator, multi-fiber formulations increased SCFA production ([~]2-fold, p = 0.001). These effects were accompanied by increased microbial biomass ([~]1.5-fold, p = 0.0007), enrichment of fiber-responsive taxa, and coordinated shifts in metabolites associated with gut-brain signaling. Collectively, these findings show that fiber blend complexity and formulation context shape microbial metabolic engagement, supporting formulation-dependent modulation of gut-derived metabolites linked to gut-brain signaling in PD. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=134 SRC="FIGDIR/small/718214v1_ufig1.gif" ALT="Figure 1"> View larger version (60K): org.highwire.dtl.DTLVardef@f84f37org.highwire.dtl.DTLVardef@18ad9borg.highwire.dtl.DTLVardef@2dd28eorg.highwire.dtl.DTLVardef@5a8da7_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2024

Amino acid competition shapes Acinetobacter baumannii gut carriage

Antimicrobial resistance is an urgent threat to human health. Asymptomatic colonization is often critical for persistence of antimicrobial-resistant pathogens. Gut colonization by the antimicrobial-resistant priority pathogen Acinetobacter baumannii is associated with increased risk of clinical infection. Ecological factors shaping A. baumannii gut colonization remain unclear. Here we show that A. baumannii and other pathogenic Acinetobacter evolved to utilize the amino acid ornithine, a non- preferred carbon source. A. baumannii utilizes ornithine to compete with the resident microbiota and persist in the gut in mice. Supplemental dietary ornithine promotes long-term fecal shedding of A. baumannii. By contrast, supplementation of a preferred carbon source--monosodium glutamate (MSG)-- abolishes the requirement for A. baumannii ornithine catabolism. Additionally, we report evidence for diet promoting A. baumannii gut carriage in humans. Together, these results highlight that evolution of ornithine catabolism allows A. baumannii to compete with the microbiota in the gut, a reservoir for pathogen spread.

microbiology↗

bioRxiv2024

Commensal Yeast Promotes Salmonella Typhimurium Virulence

Enteric pathogens engage in complex interactions with the host and the resident microbiota to establish gut colonization. Although mechanistic interactions between enteric pathogens and bacterial commensals have been extensively studied, whether and how commensal fungi affect pathogenesis of enteric infections remains largely unknown. Here we show that colonization with the common human gut commensal fungus Candida albicans worsened infections with the enteric pathogen Salmonella enterica serovar Typhimurium. Presence of C. albicans in the mouse gut increased Salmonella cecum colonization and systemic dissemination. We investigated the underlying mechanism and found that Salmonella binds to C. albicans via Type 1 fimbriae and uses its Type 3 Secretion System (T3SS) to deliver effector proteins into C. albicans. A specific effector, SopB, was sufficient to manipulate C. albicans metabolism, triggering increased arginine biosynthesis in C. albicans and the release of millimolar amounts of arginine into the extracellular environment. The released arginine, in turn, induced T3SS expression in Salmonella, increasing its invasion of epithelial cells. C. albicans deficient in arginine production was unable to increase Salmonella virulence in vitro or in vivo. In addition to modulating pathogen invasion, arginine also directly influenced the host response to infection. Arginine-producing C. albicans dampened the inflammatory response during Salmonella infection, whereas C. albicans deficient in arginine production did not. Arginine supplementation in the absence of C. albicans increased the systemic spread of Salmonella and decreased the inflammatory response, phenocopying the presence of C. albicans. In summary, we identified C. albicans colonization as a susceptibility factor for disseminated Salmonella infection, and arginine as a central metabolite in the cross-kingdom interaction between fungi, bacteria, and host.

microbiology↗

bioRxiv2024

A fungal metabolic regulator underlies infectious synergism during Candida albicans-Staphylococcus aureus intra-abdominal co-infection

Candida albicans and Staphylococcus aureus are two commonly associated pathogens that cause nosocomial infections with high morbidity and mortality. Our prior and current work using a murine model of polymicrobial intra-abdominal infection (IAI) uncovered synergistic lethality that was driven by Candida-induced upregulation of functional S. aureus -toxin leading to polymicrobial sepsis and organ damage. In order to determine the candidal effector(s) mediating enhanced virulence, an unbiased screen of C. albicans transcription factor mutants was undertaken and revealed that zcf13{Delta}/{Delta} failed to drive augmented -toxin or lethal synergism during co-infection. Using a combination of transcriptional and phenotypic profiling approaches, ZCF13 was shown to regulate genes involved in pentose metabolism, including RBK1 and HGT7 that contribute to fungal ribose catabolism and uptake, respectively. Subsequent experiments revealed that ribose inhibited the staphylococcal agr quorum sensing system and concomitantly repressed toxicity. Unlike wild-type C. albicans, zcf13{Delta}/{Delta} was unable to effectively utilize ribose during co-culture or co-infection leading to exogenous ribose accumulation and agr repression. Forced expression of RBK1 and HGT7 in the zcf13{Delta}/{Delta} mutant fully restored pathogenicity during co-infection. Collectively, our results detail the interwoven complexities of cross-kingdom interactions and highlight how intermicrobial metabolism impacts polymicrobial disease pathogenesis with devastating consequences for the host.

microbiology↗