Biology subjects

O'Meara, T.

Publications and source records attributed to O'Meara, T..

6 recordsLinked to original sources

bioRxiv2026

Candidozyma auris utilizes transferrin, but not heme-bound iron for in vivo virulence

Candidozyma auris (C. auris) is an emerging multidrug-resistant fungal pathogen, and its dissemination to the bloodstream and deep-seated organs is associated with high mortality. The limited antifungal armory and pipelines against C. auris pose a major challenge in disease management. Addressing this threat requires a deeper understanding of fungal virulence mechanisms that promote persistence and of host factors that drive susceptibility. Previous in vitro studies showed that iron enhances C. auris resistance to azoles and echinocandins, whereas iron chelation mitigates this effect. Here, we demonstrate that C. auris does not utilize cell-free heme or induce hemolysis but instead extracts and uses iron from transferrin to support growth and virulence. Deletion of the SIT1 siderophore transporter in C. auris attenuated fungal growth and reduced renal injury, while increased transferrin-iron saturation worsened disease outcomes in immunocompetent mice, highlighting the importance of transferrin-bound iron uptake. Mechanistically, C. auris exploits transferrin-bound iron to enhance ergosterol biosynthesis and activate antioxidant defenses, promoting resistance to neutrophil- and caspofungin-mediated killing. These findings identify elevated transferrin saturation as a novel host susceptibility risk factor for disseminated C. auris infection and reveal how iron availability reshapes fungal physiology to drive infection persistence.

microbiology↗

bioRxiv2026

Defining the Candidozyma auris pan-genome and essentiality

Candidozyma auris is a multi-drug resistant fungal pathogen that causes hospital outbreaks, but genetic variation and gene function in this organism remain undercharacterized. Here, we performed pangenome analysis on 695 genetically representative isolates of C. auris and found that only 2.6% of gene families varied in their presence, mainly consisting of gene loss events or clade-specific genes, highlighting the clonal nature of these strains. Using microbial genome-wide association, we identified two loci associated with altered keratinocyte adherence, including genes with unknown function. To look broadly at gene function, we developed a genome-scale insertional mutagenesis approach and identified 614 high-confidence essential genes. Nearly one-third of these genes exhibited divergent essentiality compared to the model yeasts Candida albicans and Saccharomyces cerevisiae. Together, this study highlights organism-specific biology and provides a comprehensive resource for identifying species-specific determinants of virulence and targets for antifungal drug development.

microbiology↗

bioRxiv2025

Standardizing RNA-seq Analysis of Fungal Pathogens Using BRC-Analytics and Agentic AI: A Candidozyma auris Case Study

Candidozyma auris has emerged as a critical global health threat due to multidrug resistance and healthcare-associated transmission. While RNA-seq has become the primary tool for studying C. auris pathogenesis, inconsistent use of reference genomes and bioinformatics tools complicate cross-study comparisons. Here we demonstrate how BRC-Analytics, a platform for pathogen genomics, combined with an agentic AI assistant, enables reproducible RNA-seq analysis. By re-analyzing data from two publications we achieved near-perfect correlation with published results despite annotation version differences. We addressed provenance challenges associated with using AI agents with Galaxy by forcing them to invoke Galaxys native tools rather than manipulating data directly. For custom analyses outside Galaxys toolset, we provide standalone JupyterLite notebooks that reproduce our analysis without AI involvement. This framework--combining AI-assisted automation with rigorous provenance tracking--establishes a template for standardized, reproducible fungal pathogen genomics. To the best of our knowledge, this is the first example of integration between public data repositories, reproducible analysis workflows, and agentic AI tools. Our subsequent efforts will focus on improving the seamlessness of this integration.

genomics↗

bioRxiv2025

Emergence and spread of outbreak-adapted Candidozyma auris harboring mutations in RBA1

Candidozyma auris is an emerging healthcare-associated fungal pathogen, increasingly isolated from clinical outbreaks, with a high propensity to colonize patients and the medical environment. Here, we leveraged C. auris isolates from multi-facility clinical outbreaks to identify genomic patho-adaptations promoting persistence and dissemination in the healthcare environment. Genomic and phylogenetic analyses revealed loss-of-function mutations in the uncharacterized C. auris transcription factor gene RBA1 to have independently emerged multiple times within these outbreaks. We demonstrate loss of RBA1 increases C. auris adhesion to plastic and human keratinocytes, enhances biofilm formation, and exacerbates fungal burden in a mouse model of catheter-associated urinary tract infection. Finally, we uncover mutations in RBA1 have emerged during multiple C. auris outbreaks across the globe, and that RBA1 mutant lineages are present among large ongoing clinical outbreaks. These results reveal loss-of-function mutations in C. auris RBA1 as a novel and clinically relevant genetic determinant of enhanced outbreak characteristics.

microbiology↗

bioRxiv2024

Gut and oral microbial community characterization from women with breast cancer, women with ductal carcinoma in situ, and healthy women reveals differences in gut but not oral microbiota

This study characterized and compared the fecal and oral microbiota from women with early-stage breast cancer (BC), women with ductal carcinoma in situ (DCIS), and healthy women. Fecal and oral samples were collected from newly diagnosed patients prior to any therapy and characterized using 16S rRNA sequencing. Measures of gut microbial alpha diversity were significantly lower in the BC versus healthy cohort. Beta diversity differed significantly between the BC or DCIS and healthy groups and several differentially abundant taxa were identified. Clustering (non-negative matrix factorization) of the gut microbiota identified 5 bacterial guilds dominated by either Prevotella, Enterobacteriaceae, Akkermansia, Clostridiales, or Bacteroides. The Bacteroides and Enterobacteriaceae guilds were significantly more abundant in the BC cohort compared to healthy controls whereas the Clostridiales guild was more abundant in the healthy group. Finally, prediction of functional pathways identified 23 pathways that differed between the BC and healthy gut microbiota including lipopolysaccharide biosynthesis, glycan biosynthesis and metabolism, lipid metabolism, and sphingolipid metabolism. In contrast to the gut microbiomes, there were no significant differences in alpha or beta diversity in the oral microbiomes and very few differentially abundant taxa were observed. NMF analysis of the oral microbiota samples identified 7 guilds dominated by Veillonella, Prevotella, Gemellaceae, Haemophilus, Neisseria, Propionibacterium, and Streptococcus, however, none of these guilds were differentially associated with the different cohorts. Our results suggest that alterations in the gut microbiota, but not oral microbiota, may provide the basis for interventions targeting the gut microbiome to improve treatment outcomes and long-term prognosis. IMPORTANCEEmerging evidence suggests that the gut microbiota may play a role in breast cancer. Few studies have evaluated both the gut and oral microbiomes in women with breast cancer (BC) and none have characterized these microbiomes in women with ductal carcinoma in situ (DCIS). We surveyed the gut and oral microbiomes from women with BC or DCIS and healthy women and identified compositional and functional features of the gut microbiota that differed between these cohorts. In contrast, very few differential features were identified in the oral microbiota. These findings suggest that the oral microbiome is unlikely to be an effective risk marker for DCIS or breast cancer compared to the gut microbiome. Understanding the role of gut bacteria in BC and DCIS may open up new opportunities for the development of novel markers for early detection (or markers of susceptibility) as well as new strategies for prevention and/or treatment.

microbiology↗

bioRxiv2023

Groundwater redox dynamics across the terrestrial-aquatic interface of Lake Erie coastal ecosystems

Groundwater biogeochemistry in coastal areas is spatially and temporally dynamic because fluctuations in groundwater level may cause alternate redox between distinct hydrological conditions. Recent studies have proposed connections between biogeochemistry and large-scale hydrological processes, specifically focusing on the role of redox-active compounds in changing the oxidation state during flooding and draining events. While water saturation generally results in a shift of redox-active compounds from electron donors to acceptors, the specific mechanisms underlying the transition of groundwater between oxidizing and reducing conditions in response to water level fluctuations are uncertain. To determine the effects of groundwater levels on redox dynamics, we monitored groundwater redox potential across the terrestrial-aquatic interface in Lake Erie coastal areas throughout the high and low-water seasons. In contrast to previously observed responses to flooding in soils, our results revealed patterns of oxidizing redox potentials during high-water and reducing during low-water periods. Furthermore, short-term fluctuations in water table levels significantly impacted the redox potential of groundwater when dissolved oxygen increased, and redox dynamics displayed voltage hysteresis in most events. Based on these findings, we propose that for improved predictions of microbial functions and biogeochemical cycles, redox-informed models should incorporate the antagonistic changes in groundwater redox balance compared to soils and consider the time lags in redox fluctuations. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=92 SRC="FIGDIR/small/544684v1_figu1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@4d7a19org.highwire.dtl.DTLVardef@8b2b92org.highwire.dtl.DTLVardef@d9bc11org.highwire.dtl.DTLVardef@ca3e13_HPS_FORMAT_FIGEXP M_FIG Graphical AbstractConceptual diagram of groundwater redox fluctuations in coastal ecosystems. Large redox fluctuations are derived by dissolved oxygen inputs and smaller more frequent redox fluctuations are led by redox sensitive species leaching from topsoil. C_FIG

ecology↗