Multistate Epidemiologic Description of Histoplasmosis in the United States, 2004–2015

Armstrong, Paige A.; Benedict, Kaitlin; Haselow, Dirk; Fields, Virgie; Jackson, Brendan R; Austin, Connie; Ireland, Malia; Signs, Kimberly; Fialkowski, Veronica; Patel, Reema; Pedati, Caitlin; Iwen, Peter C.; Dobbs, Thomas; Anderson, Jannifer; Gibbons-Burgener, Suzanne; Warren, Kim; Davidson, Sherri; McIntyre, Mary G.; Midla, Joanne; Luong, Nhiem

doi:10.1093/ofid/ofw194.33

Cited by 2 publications

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“…Histoplasma capsulatum is one of the most common thermally dimorphic fungi, and though classic areas of endemicity along the Ohio and Mississippi River Valleys have been described, there is increasing recognition of histoplasmosis outside of these areas [1, 2]. H. capsulatum is a rare cause of infectious endocarditis, with only 58 previously described cases [3, 4].…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Importance of Hyphae on Heart Valve Tissue in Histoplasma Endocarditis and Treatment With Isavuconazole

Wiley

Woodworth

Jacob

et al. 2017

Open Forum Infectious Diseases

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Section: Discussionmentioning

confidence: 99%

Diagnostic Importance of Hyphae on Heart Valve Tissue in Histoplasma Endocarditis and Treatment With Isavuconazole

Wiley

Woodworth

Jacob

et al. 2017

Open Forum Infectious Diseases

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“…Approximately 60-90% of individuals residing in the Ohio and Mississippi River Valleys are thought to have been exposed to Histoplasma, with the disease histoplasmosis reaching an incidence of up to 4.3 cases per 100,000 population in endemic regions and a mortality rate of up to 7% (2,3). Histoplasma grows saprophytically with a filamentous morphology in the soil that generates asexual spores termed macro-and microconidia.…”

Section: Introductionmentioning

confidence: 99%

Recyclable CRISPR/Cas9 mediated gene disruption and deletions inHistoplasma

Joehnk

Ali

Voorhies

et al. 2023

Preprint

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Targeted gene disruption is challenging in the dimorphic fungal pathogenHistoplasmadue to the low frequency of homologous recombination. Transformed DNA is either integrated ectopically into the genome or maintained extra chromosomally by the de novo addition of telomeric sequences. Based on a system developed inBlastomyces, we adapted a CRISPR/Cas9 system to facilitate targeted gene disruption inHistoplasmawith high efficiency. We express a codon-optimized version of Cas9 as well as guide RNAs from a single ectopic vector carrying a selectable marker. Once the desired mutation is verified, one can screen for isolates that have lost the Cas9 vector by simply removing the selective pressure. Multiple mutations can then be generated in the same strain by retransforming the Cas9 vector carrying different guides. We used this system to disrupt a number of target genes including RYP2 and SRE1 where loss-of-function mutations could be monitored visually by colony morphology or color, respectively. Interestingly, expression of two guide RNAs targeting the 5′ and 3′ ends of a gene allowed isolation of deletion mutants where the sequence between the guide RNAs was removed from the genome. Whole-genome sequencing showed that the frequency of off-target mutations associated with the Cas9 nuclease was negligible. Finally, we increased the frequency of gene disruption by using an endogenousHistoplasmaregulatory sequence to drive guide RNA expression. These tools transform our ability to generate targeted mutations inHistoplasma.

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Multistate Epidemiologic Description of Histoplasmosis in the United States, 2004–2015

Cited by 2 publications

References 0 publications

Diagnostic Importance of Hyphae on Heart Valve Tissue in Histoplasma Endocarditis and Treatment With Isavuconazole

Diagnostic Importance of Hyphae on Heart Valve Tissue in Histoplasma Endocarditis and Treatment With Isavuconazole

Recyclable CRISPR/Cas9 mediated gene disruption and deletions inHistoplasma

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