Biology subjects

Feistel, D. J.

Publications and source records attributed to Feistel, D. J..

4 recordsLinked to original sources

bioRxiv2026

Genomovar-level resolution reveals rapid pathotype switching and genomovar-specific disease potential in diarrheagenic Escherichia coli populations in northern Ecuador

Diarrheagenic Escherichia coli (DEC) pathotypes are commonly defined by molecular detection of discrete virulence genes, yet how quickly these diagnostic genes emerge and move among co-circulating lineages remain unclear. Here, we classified 248 whole-genome-sequenced E. coli isolates from the EcoZUR case-control study in northern Ecuador into intra-species genomovar units using the recently described 99.5% ANI threshold. This framework exposed cryptic population structure, revealing that single sequence types, representing identical multilocus sequence types (MLST), can harbor multiple distinct genomovars. Within individual genomovars, we observed a few cases of different pathotypes among isolates showing ~99.7% ANI (and many such cases between genomovars). Coupled with synteny and phylogeny analyses that revealed pervasive incongruences between pathotype-diagnostic virulence genes and the core genome, these findings suggest recent horizontal gene transfer as the primary driver of pathotype evolution. Virulence gene profiling further revealed that accessory virulence repertoires are hierarchically structured by phylogroup across pathotypes, with genomovars assigned to phylogroups B2 and D exhibiting more conserved virulence architectures than those in phylogroup A and B1. Among DAEC isolates specifically, the B2- and D-associated genomovars showed elevated diarrhea-association rates relative to their phylogroup A counterparts. Rare virulence genes, including Type VI secretion systems, further distinguished diarrhea-associated from asymptomatic genomovars. These findings demonstrate that, although there seems to be within-lineage (phylogroup) conservation of virulence, pathotype identity is a labile state defined by horizontally acquired virulence genes at the genomovar level, and that the genomovar framework provides a biologically meaningful unit for linking intra-species diversity to pathogenic potential and outbreaks.

genomics↗

bioRxiv2022

A natural definition for a bacterial strain and clonal complex

Large-scale surveys of prokaryotic communities (metagenomes) as well as isolate genomes have revealed that their diversity is predominantly organized in sequence-discrete units that may be equated to species. Specifically, genomes of the same species commonly show genome-aggregate average nucleotide identity (ANI) >95% among themselves and ANI <90% to members of other species, while genomes showing ANI 90-95% are comparatively rare. However, it remains unclear if such "discontinuities" or gaps in ANI values can be observed within species and thus, used to advance and standardize intra-species units such as strains and sequence types. By analyzing 18,123 complete isolate genomes from 330 bacterial species with at least ten genome representatives each as well as available long-read metagenomes, we show that such a discontinuity exists between 99.2-99.8% (mean 99.5%) ANI. The 99.5% ANI threshold is largely consistent with how sequence types have been defined in previous epidemiological studies but provides clusters with [~]20% higher accuracy in terms of evolutionary and gene-content relatedness of the grouped genomes, while strains should be consequently defined at higher ANI values (>99.99% proposed). Collectively, our results should facilitate future micro-diversity studies across clinical or environmental settings because they provide a more natural definition of intra-species units of diversity.

microbiology↗

bioRxiv2019

Fungal virulence depends on interactions between pathogen ploidy and genetic background in healthy and immunocompromised hosts

Studying fungal virulence is often challenging and frequently depends on many contexts, including host immune status and pathogen genetic background. However, ploidy has often been overlooked when studying virulence in eukaryotic pathogens. Since fungal pathogens, including the human opportunistic pathogen Candida albicans, can display extensive ploidy variation, assessing how ploidy impacts virulence has important clinical relevance. Here, we assessed how C. albicans ploidy and genetic background impact virulence phenotypes in both healthy and immunocompromised nematode hosts. In addition to reducing overall host survival, Candida negatively impacted host reproduction, which allowed us to survey lethal and non-lethal virulence phenotypes. While we did not detect any global differences in virulence between diploid and tetraploid pathogens, there were significant interactions between ploidy and C. albicans genetic background, regardless of host immune function.

genetics↗

bioRxiv2018

A novel virulence phenotype rapidly assesses Candida fungal pathogenesis in healthy and immunocompromised Caenorhabditis elegans hosts

The yeast Candida albicans is an opportunistic pathogen of humans, meaning that despite commensal interactions with its host, it can transition to a harmful pathogen. While C. albicans is the predominant species isolated in the human mycobiome and implicated in fungal infection, infections due to non-albicans Candida species are rapidly rising. Studying the factors that contribute to virulence is often challenging and frequently depends on many contexts including host immune status and pathogen genetic background. Here, we utilize the nematode Caenorhabditis elegans as a perspicuous and efficient model host system to study fungal infections of Candida pathogens. We find that in addition to reducing lifetime host survival, exposure to C. albicans results in delayed reproduction, which significantly reduced lineage growth over multiple generations. Furthermore, we assessed fungal pathogen virulence in C. elegans hosts compromised for innate immune function and detected increased early mortality, reduced brood sizes and delayed reproduction relative to infected healthy hosts. Importantly, by assessing virulence in both healthy and immunocompromised host backgrounds we reveal the pathogen potential in non-albicans Candida species. Taken together, we present a novel lineage growth assay to measure reduction in host fitness associated with fungal infection and demonstrate significant interactions between pathogen and host immune function that contribute to virulence.

microbiology↗