Dataset Information

Recent admixture between species of the fungal pathogen Histoplasma.

ABSTRACT: Hybridization between species of pathogens has the potential to speed evolution of virulence by providing the raw material for adaptation through introgression or by assembling new combinations of virulence traits. Fungal diseases are a source high morbidity, and remain difficult to treat. Yet the frequency of hybridization between fungal species has rarely been explored, and the functional role of introgressed alleles remains largely unknown. Histoplasma mississippiense and H. ohiense are sympatric throughout their range in North America and have distinct virulence strategies, making them an ideal system to examine the role introgression may play in fungal pathogens. We identified introgressed tracts in the genomes of a sample of H. mississippiense and H. ohiense isolates. We found strong evidence in each species for recent admixture, but introgressed alleles were present at low frequencies, suggesting that they were deleterious. Consistent with this, coding and regulatory sequences were strongly depleted within introgressed regions, whereas intergenic regions were enriched, indicating that functional introgressed alleles were frequently deleterious in their new genomic context. Surprisingly, we found only two isolates with substantial admixture: the H. mississippiense and H. ohiense genomic reference strains, WU24 and G217B, respectively. Our results show that recent admixture has occurred, that it is frequently deleterious and that conclusions based on studies of the H. mississippiense and H. ohiense type strains should be revisited with more representative samples from the genus.

SUBMITTER: Maxwell CS

PROVIDER: S-EPMC6121842 | biostudies-other | 2018 Jun

REPOSITORIES: biostudies-other

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Recent admixture between species of the fungal pathogen Histoplasma.

Maxwell Colin S CS Sepulveda Victoria E VE Turissini David A DA Goldman William E WE Matute Daniel R DR

Evolution letters 20180622 3

Hybridization between species of pathogens has the potential to speed evolution of virulence by providing the raw material for adaptation through introgression or by assembling new combinations of virulence traits. Fungal diseases are a source high morbidity, and remain difficult to treat. Yet the frequency of hybridization between fungal species has rarely been explored, and the functional role of introgressed alleles remains largely unknown. Histoplasma mississippiense and H. ohiense ...[more]

PMID: 30283677

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Project description:Histoplasmosis is an endemic mycosis that often presents as a respiratory infection in immunocompromised patients. Hundreds of thousands of new infections are reported annually around the world. The etiological agent of the disease, Histoplasma, is a dimorphic fungus commonly found in the soil where it grows as mycelia. Humans can become infected by Histoplasma through inhalation of its spores (conidia) or mycelial particles. The fungi transition into the yeast phase in the lungs at 37°C. Once in the lungs, yeast cells reside and proliferate inside alveolar macrophages. Genomic work has revealed that Histoplasma is composed of at least five cryptic phylogenetic species that differ genetically. Three of those lineages have received new names. Here, we evaluated multiple phenotypic characteristics (colony morphology, secreted proteolytic activity, yeast size, and growth rate) of strains from five of the phylogenetic species of Histoplasma to identify phenotypic traits that differentiate between these species: Histoplasma capsulatum sensu stricto, Histoplasma ohiense, Histoplasma mississippiense, Histoplasma suramericanum, and an African lineage. We report diagnostic traits for three species. The other two species can be identified by a combination of traits. Our results suggest that (i) there are significant phenotypic differences among the cryptic species of Histoplasma and (ii) those differences can be used to positively distinguish those species in a clinical setting and for further study of the evolution of this fungal pathogen.IMPORTANCEIdentifying species boundaries is a critical component of evolutionary biology. Genome sequencing and the use of molecular markers have advanced our understanding of the evolutionary history of fungal pathogens, including Histoplasma, and have allowed for the identification of new species. This is especially important in organisms where morphological characteristics have not been detected. In this study, we revised the taxonomic status of the four named species of the genus Histoplasma, H. capsulatum sensu stricto (ss), H. ohiense, H. mississippiense, and H. suramericanum, and propose the use of species-specific phenotypic traits to aid their identification when genome sequencing is not available. These results have implications not only for evolutionary study of Histoplasma but also for clinicians, as the Histoplasma species could determine the outcome of disease and treatment needed.

Project description:Regulation of iron acquisition genes is critical for microbial survival under both iron-limiting conditions (to acquire essential iron) and iron-replete conditions (to limit iron toxicity). In fungi, iron acquisition genes are repressed under iron-replete conditions by a conserved GATA transcriptional regulator. Here we investigate the role of this transcription factor, Sre1, in the cellular responses of the fungal pathogen Histoplasma capsulatum to iron. We showed that cells in which SRE1 levels were diminished by RNA interference were unable to repress siderophore biosynthesis and utilization genes in the presence of abundant iron, and thus produced siderophores even under iron-replete conditions. Mutation of a GATA-containing consensus site found in the promoters of these genes also resulted in inappropriate gene expression under iron-replete conditions. Microarray analysis comparing control and SRE1-depleted strains under conditions of iron limitation or abundance revealed both iron-responsive genes and Sre1-dependent genes, which comprised distinct but overlapping sets. Iron-responsive genes included putative oxidoreductases, metabolic and mitochondrial enzymes, superoxide dismutase, and nitrosative-stress response genes; Sre1-dependent genes were of diverse function. Genes regulated by iron levels and Sre1 included all of the siderophore biosynthetic genes, a gene involved in reductive iron acquisition, an iron-responsive transcription factor, and two catalases. Based on transcriptional profiling and phenotypic analyses, we conclude that Sre1 plays a critical role in the regulation of both traditional iron-responsive genes and iron-independent pathways such as regulation of cell morphology. These data highlight the evolving realization that the effect of Sre1 orthologs on fungal biology extends beyond the iron regulon. For microarray studies, initial cultures of HcLH120 (Control RNAi-1) or 123 (SRE1 RNAi-2) yeast cells were grown in 5 mL HMM, and then passaged 1:25 into 100 mL HMM. After 2 days of growth, the cultures were pelleted, washed in 100 mL of PBS, resuspended in 100 mL of mRPMI pH 6.5 and diluted to an OD600~2 in 1 L of mRPMI. After 24 hours of growth, 200 mL of culture was harvested for each of the three zero time points. Then the cultures were split into 2 X 400 mL, and 10 uM FeSO4 (final concentration) was added to one set of cultures. At each time point (.5, 1, 4, or 8 hours), 100 mL of culture was harvested for RNA extraction.

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Recent admixture between species of the fungal pathogen Histoplasma.

Publications

Recent admixture between species of the fungal pathogen <i>Histoplasma</i>.

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