ORCID Profile
0000-0002-2225-5122
Current Organisations
The University of Texas at Austin
,
The University of Texas Health Science Center at San Antonio
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Publisher: American Association of Zoo Veterinarians
Date: 06-2017
Publisher: Naturalis Biodiversity Center
Date: 29-06-2015
Publisher: American Society for Microbiology
Date: 02-2016
DOI: 10.1128/AAC.02456-15
Abstract: The CLSI epidemiological cutoff values (ECVs) of antifungal agents are available for various Candida spp., Aspergillus spp., and the Mucorales. However, those categorical endpoints have not been established for Fusarium spp., mostly due to the difficulties associated with collecting sufficient CLSI MICs for clinical isolates identified according to the currently recommended molecular DNA-PCR-based identification methodologies. CLSI MIC distributions were established for 53 Fusarium dimerum species complex (SC), 10 F. fujikuroi , 82 F. proliferatum , 20 F. incarnatum-F. equiseti SC, 226 F. oxysporum SC, 608 F. solani SC, and 151 F. verticillioides isolates originating in 17 laboratories (in Argentina, Australia, Brazil, Canada, Europe, Mexico, and the United States). According to the CLSI guidelines for ECV setting, ECVs encompassing ≥97.5% of pooled statistically modeled MIC distributions were as follows: for hotericin B, 4 μg/ml ( F. verticillioides ) and 8 μg/ml ( F. oxysporum SC and F. solani SC) for posaconazole, 2 μg/ml ( F. verticillioides ), 8 μg/ml ( F. oxysporum SC), and 32 μg/ml ( F. solani SC) for voriconazole, 4 μg/ml ( F. verticillioides ), 16 μg/ml ( F. oxysporum SC), and 32 μg/ml ( F. solani SC) and for itraconazole, 32 μg/ml ( F. oxysporum SC and F. solani SC). Insufficient data precluded ECV definition for the other species. Although these ECVs could aid in detecting non-wild-type isolates with reduced susceptibility to the agents evaluated, the relationship between molecular mechanisms of resistance (gene mutations) and MICs still needs to be investigated for Fusarium spp.
Publisher: Proceedings of the National Academy of Sciences
Date: 25-10-2016
Abstract: New antifungal drugs that act via novel mechanisms are urgently needed to combat the high mortality of invasive fungal disease and the emergence of resistance to existing therapies. We describe the discovery, structure, activity, and mechanism of action of F901318, a new antifungal agent. A member of a novel class of antifungals, the orotomides, F901318 acts via inhibition of dihydroorotate dehydrogenase, an enzyme of de novo pyrimidine biosynthesis. F901318 is currently in clinical development for the treatment of invasive aspergillosis.
Publisher: Scientific Societies
Date: 07-2021
DOI: 10.1094/PHYTO-08-20-0330-LE
Abstract: Scientific communication is facilitated by a data-driven, scientifically sound taxonomy that considers the end-user’s needs and established successful practice. In 2013, the Fusarium community voiced near unanimous support for a concept of Fusarium that represented a clade comprising all agriculturally and clinically important Fusarium species, including the F. solani species complex (FSSC). Subsequently, this concept was challenged in 2015 by one research group who proposed iding the genus Fusarium into seven genera, including the FSSC described as members of the genus Neocosmospora, with subsequent justification in 2018 based on claims that the 2013 concept of Fusarium is polyphyletic. Here, we test this claim and provide a phylogeny based on exonic nucleotide sequences of 19 orthologous protein-coding genes that strongly support the monophyly of Fusarium including the FSSC. We reassert the practical and scientific argument in support of a genus Fusarium that includes the FSSC and several other basal lineages, consistent with the longstanding use of this name among plant pathologists, medical mycologists, quarantine officials, regulatory agencies, students, and researchers with a stake in its taxonomy. In recognition of this monophyly, 40 species described as genus Neocosmospora were recombined in genus Fusarium, and nine others were renamed Fusarium. Here the global Fusarium community voices strong support for the inclusion of the FSSC in Fusarium, as it remains the best scientific, nomenclatural, and practical taxonomic option available.
Publisher: American Society for Microbiology
Date: 18-05-2021
DOI: 10.1128/AAC.02344-20
Abstract: Coccidioides spp. are important pathogens in regions where they are endemic, and new treatment options are needed. Here, isavuconazonium sulfate (ISAVUSULF) and fluconazole (FLU) were evaluated in experimental disseminated coccidioidomycosis to characterize drug exposures associated with efficacy. Broth macrodilution was performed on Coccidioides isolates to measure minimal effective concentrations (MEC) and minimal fungicidal concentrations (MFC).
Publisher: American Society for Microbiology
Date: 02-2013
DOI: 10.1128/AAC.01624-12
Abstract: Miltefosine is an alkyl phosphocholine with good oral bioavailability and in vitro activity against Cryptococcus species that has gained interest as an additional agent for cryptococcal infections. Our objective was to further evaluate the in vivo efficacy of miltefosine in experimental in vivo models of cryptococcal meningoencephalitis and disseminated cryptococcosis. Mice were infected intracranially or intravenously with either C. neoformans USC1597 or H99. Miltefosine treatment (1.8 to 45 mg/kg of body weight orally once daily) began at either 1 h or 1 day postinoculation. Fluconazole (10 mg/kg orally twice daily) or hotericin B deoxycholate (3 mg/kg intraperitoneally once daily) served as positive controls. In our standard models, miltefosine did not result in significant improvements in survival or reductions in fungal burden against either C. neoformans isolate. There was a trend toward improved survival with miltefosine at 7.2 mg/kg against disseminated cryptococcosis with the H99 strain but only at a low infecting inoculum. In contrast, both fluconazole and hotericin B significantly improved survival in mice with cryptococcal meningoencephalitis and disseminated cryptococcosis due to USC1597. Amphotericin B also improved survival against both cryptococcal infections caused by H99. Combination therapy with miltefosine demonstrated neither synergy nor antagonism in both models. These results demonstrate limited efficacy of miltefosine and suggest caution with the potential use of this agent for the treatment of C. neoformans infections.
Publisher: Wiley
Date: 13-08-2021
DOI: 10.1111/JVIM.16244
Abstract: Clinical features, treatment, and outcome of opportunistic infections with Rasamsonia spp., a nonpigmented filamentous mold, are not well documented in dogs. Describe clinical, radiographic, pathologic features, and outcome of dogs with disseminated Rasamsonia species complex infections. Eight client‐owned dogs. Retrospective case series. Medical records were reviewed to describe signalment, history, clinicopathologic and imaging findings, microbiologic and immunologic results, cyto‐ and histopathologic diagnoses, treatment, and outcome. Presenting complaints were nonspecific with anorexia (n = 5) and back pain (n = 4) most common. Five dogs were German Shepherd dogs. Six dogs had multifocal discospondylitis and 2 had pleural effusion. Six dogs had Rasamsonia piperina and 2 had Rasamsonia argillacea infections with isolates identified using DNA sequencing. Rasamsonia spp. were isolated by urine culture in 5 of 7 dogs. Five of 6 dogs had positive serum Aspergillus galactomannan antigen enzyme immunoassay (EIA) results. Median survival time was 82 days, and 317 days for dogs that survived to discharge. Four died during initial hospitalization (median survival, 6 days). All isolates had low minimum effective concentrations (MECs) to echinocandins with variable minimum inhibitory concentrations (MICs) for azole antifungal drugs. Rasamsonia spp. infections in dogs are associated with multisystemic disease involving the vertebral column, central nervous system, kidneys, spleen, lymph nodes, lungs, and heart. The infection shares clinical features with other systemic mold infections and can be misidentified when using phenotypical microbiologic methods. Molecular techniques are required to identify the organism and guide appropriate antifungal treatment.
Publisher: Naturalis Biodiversity Center
Date: 09-11-2180
DOI: 10.3767/PERSOONIA.2019.42.08
Abstract: Mycoleptodiscus includes plant pathogens, animal opportunists, saprobic and endophytic fungi. The present study presents the first molecular phylogeny and revision of the genus based on four loci, including ITS, LSU, rpb2 , and tef1 . An extensive collection of Mycoleptodiscus cultures, including ex-type strains from the CBS, IMI, MUCL, BRIP, clinical isolates from the USA, and fresh isolates from Brazil and Spain, was studied morphologically and phylogenetically to resolve their taxonomy. The study showed that Mycoleptodiscus sensu lato is polyphyletic. Phylogenetic analysis places Mycoleptodiscus in Muyocopronales ( Dothideomycetes ), together with Arxiella , Leptodiscella , Muyocopron , Neocochlearomyces , and Paramycoleptodiscus . Mycoleptodiscus terrestris , the type species, and M. sphaericus are reduced to synonyms, and one new species is introduced, M. suttonii. Mycoleptodiscus atromaculans , M. coloratus , M. freycinetiae , M. geniculatus , M. indicus , M. lateralis (including M. unilateralis and M. variabilis as its synonyms) and M. taiwanensis belong to Muyocopron ( Muyocopronales , Dothideomycetes ), and M. affinis , and M. lunatus to Omnidemptus ( Magnaporthales , Sordariomycetes ). Based on phylogenetic analyses we propose Muyocopron alcornii sp. nov., a fungus associated with leaf spots on Epidendrum sp. ( Orchidaceae ) in Australia, Muyocopron zamiae sp. nov. associated with leaf spots on Zamia ( Zamiaceae ) in the USA, and Omnidemptus graminis sp. nov. isolated from a grass ( Poaceae ) in Spain. Furthermore, Neomycoleptodiscus venezuelense gen. & sp. nov. is introduced for a genus similar to Mycoleptodiscus in Muyocopronaceae .
Location: United States of America
No related grants have been discovered for Nathan Wiederhold.