- Antifungal resistance and susceptibility
- Fungal Infections and Studies
- Pneumocystis jirovecii pneumonia detection and treatment
- Plant Pathogens and Fungal Diseases
- Fungal Biology and Applications
- Fungal and yeast genetics research
- Nail Diseases and Treatments
- Synthesis and Biological Evaluation
- Protist diversity and phylogeny
- Probiotics and Fermented Foods
- Plant-Microbe Interactions and Immunity
- Trypanosoma species research and implications
- Biochemical and Molecular Research
- Parasitic Infections and Diagnostics
- RNA modifications and cancer
- Mycotoxins in Agriculture and Food
- Mycorrhizal Fungi and Plant Interactions
- Antimicrobial Peptides and Activities
- Peptidase Inhibition and Analysis
- Nematode management and characterization studies
- Microbial Natural Products and Biosynthesis
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- Glycosylation and Glycoproteins Research
- Microbial Fuel Cells and Bioremediation
University of Missouri–Kansas City
2013-2024
Center for Infectious Disease Research
2003-2014
University of Washington
2002-2011
Seattle University
1999-2011
National Institute of Standards and Technology
2009
Iogen Corporation
2002
University of Alabama at Birmingham
2002
Fred Hutch Cancer Center
1997-1999
Infectious Disease Research Institute
1999
Faculty of Public Health
1998
Resistance to antifungal drugs, specifically azoles such as fluconazole, in the opportunistic yeast Candida albicans has become an increasing problem human immunodeficiency virus (HIV)-infected individuals. The molecular mechanisms responsible for this resistance have only recently apparent and can include alterations target enzyme of azole drugs (lanosterol 14alpha demethylase [14DM]), or various efflux pumps from both ABC transporter major facilitator gene families. To determine which...
The prophylactic use of fluconazole is common in blood and marrow transplant (BMT) recipients. To evaluate how has influenced the development azole resistance candidemia, weekly mouthwashings were done, susceptibility was determined for 1475 colonizing invasive isolates obtained from patients undergoing BMT. Of 585 patients, 256 (44%) colonized with Candida species during course these, 136 (53%) had at least 1 mouthwashing sample that yielded other than C. albicans on culture. Only 4.6%...
ABSTRACT Resistance to azole antifungals continues be a significant problem in the common fungal pathogen Candida albicans . Many of molecular mechanisms resistance have been defined with matched sets susceptible and resistant clinical isolates from same strain. Mechanisms that identified include alterations gene encoding target enzyme ERG11 or overexpression efflux pump genes including CDR1 , CDR2 MDR1 In present study, collection unmatched C. was analyzed for known by standard methods. The...
Candida albicans is both a member of the healthy human microbiome and major pathogen in immunocompromised individuals. Infections are typically treated with azole inhibitors ergosterol biosynthesis often leading to drug resistance. Studies clinical isolates have implicated multiple mechanisms resistance, but focused on large-scale aberrations or candidate genes, do not comprehensively chart genetic basis adaptation. Here, we leveraged next-generation sequencing analyze 43 from 11 oral...
ABSTRACT The major cause of athlete’s foot is Trichophyton rubrum , a dermatophyte or fungal pathogen human skin. To facilitate molecular analyses the dermatophytes, we sequenced T. and four related species, tonsurans equinum Microsporum canis gypseum . These species differ in host range, mating, disease progression. genomes are highly colinear yet contain gene family expansions not found other human-associated fungi. Dermatophyte enriched for families containing LysM domain, which binds...
ABSTRACT Ergosterol (ERG) is a critical sterol in the cell membranes of fungi, and its biosynthesis tightly regulated by 25 known enzymes along ERG production pathway. The effects changes expression each enzyme Saccharomyces cerevisiae were analyzed use gene deletion or plasmid-borne overexpression constructs. strains overexpressing pathway genes examined for doubling time responses to variety stress agents. In addition, tested alterations antifungal drug susceptibility. data show that...
Candida auris is an emerging multidrug-resistant pathogen of global concern, known to be responsible for outbreaks on six continents and commonly resistant antifungals. While the vast majority clinical C. isolates are highly fluconazole, essential part available antifungal arsenal, very little about mechanisms contributing resistance. In this work, we show that mutations in transcription factor TAC1B significantly contribute fluconazole These studies demonstrated can arise rapidly vitro upon...
Candida auris is an emerging fungal infection of humans and particularly problematic because it multi-drug resistant difficult to treat. It also known be spread from person by contact can remain on surfaces for long periods time. In this report, a dog in shelter Kansas found colonized with . This the first study document presence pet, C. non-human mammal United States, report isolate within state Kansas. The pet raises possibility zoonotic transmission pets human or vice versa.
Azole resistance in the pathogenic yeast Candida albicans is an emerging problem human immunodeficiency virus (HIV)-infected population. The target enzyme of azole drugs lanosterol 14alpha demethylase (Erg16p), a cytochrome P-450 biosynthetic pathway ergosterol. Biochemical analysis demonstrates that Erg16p became less susceptible to fluconazole isolate 13 series isolates from HIV-infected patient. PCR-single-strand conformation polymorphism (PCR-SSCP) was used scan for genomic alterations...
We have localized the six ribosomal RNAs (rRNAs) which encode 28S rRNA region of Trypanosoma brucei. These rRNAs include two large rRNAs, α (approx. 1840 nt) and β 1570 nt), four small approximate sizes 220, 180, 140 70 nt. Three these (180, 140) are found at 3' end region. Sequence analysis this area shows that three Domain VII, last domain secondary structure in eukaryotes. Hybridization labeled nascent RNA to qloned repeat unit S1 nuclease protection putative precursors show transcription...
Filamentous fungi have a sturdy cell wall which is resistant to the usual DNA extraction procedures. We determined procedure with greatest yield of high quality fungal and least predilection for cross-contamination equipment between specimens. Each six methods was performed using Aspergillus fumigatus hyphae. The were: (1) glass bead pulverization vortexing; (2) grinding mortar pestle followed by pulverization; (3) 1% hydroxyacetyl trimethyl ammonium bromide (CTAB) buffer in water bath...
For the pathogenic yeast Candida albicans, secreted aspartyl proteinase (Sap) activity has been correlated with virulence. A family consisting of at least eight SAP genes can be drawn upon to produce Sap enzymatic activity. In this study, levels Sap1, Sap2, and Sap3 isoenzymes were monitored under a variety growth conditions for several strains, including strain WO-1, which alternates between two switch phenotypes, white (W) opaque (O). When cultured proteinase-inducing conditions, most...
ABSTRACT Resistance to fluconazole is becoming an increasing problem in the management of oropharyngeal candidiasis human immunodeficiency virus-infected patients. Strains obtained from five patients developed decreased susceptibility over time. DNA strain typing confirmed high degree relatedness among isolates one patient and variability different Expression genes involved development resistance was monitored each isolate using probes specific for ERG11 (lanosterol 14α-demethylase), MDR1 (a...
ABSTRACT In Candida albicans , drug resistance to clinically important antifungal drugs may be regulated through the action of transcription factors in a manner that or not similar regulation Saccharomyces cerevisiae . A search C. genome identified single homolog S. factor genes UPC2 ( ScUPC2 ) and ECM22 ScECM22 have been associated with ergosterol biosynthesis. Sequence analysis this CaUPC2 gene identifies two domains, an anchoring transmembrane domain region containing multiple nuclear...
Abstract Background Millions of humans and animals suffer from superficial infections caused by a group highly specialized filamentous fungi, the dermatophytes, which exclusively infect keratinized host structures. To provide broad insights into molecular basis pathogenicity-associated traits, we report first genome sequences two closely phylogenetically related Arthroderma benhamiae Trichophyton verrucosum , both induce inflammatory in humans. Results 97% 22.5 megabase A. T. are...
ABSTRACT Secreted aspartyl proteinases are putative virulence factors in Candida infections. albicans possesses at least nine members of a SAP gene family, all which have been sequenced. Although the expression genes has extensively characterized under laboratory growth conditions, no studies analyzed detail vivo these human oral colonization and infection. We developed reliable sensitive procedure to detect C. mRNA from whole saliva patients with infection those asymptomatic carriage. The...
Dermatophytes are prevalent causes of cutaneous mycoses and, unlike many other fungal pathogens, able to cause disease in immunocompetent individuals. They infect keratinized tissue such as skin, hair, and nails, resulting tinea infections, including ringworm. Little is known about the molecular mechanisms that underlie ability these organisms establish maintain infection. The recent availability genome sequence information improved genetic manipulation have enabled researchers begin...
Dermatophytes belonging to the Trichophyton and Arthroderma genera cause skin infections in humans animals. From genome sequencing data, we mined a conserved gene cluster among dermatophytes that are homologous one produces an immunosuppressive polyketide Aspergillus fumigatus. Using recombination-based cloning strategy yeast, constructed fungal heterologous expression vectors encode cryptic clusters. When integrated into model nidulans host, structurally related compound neosartoricin B was...
An IMP dehydrogenase gene was isolated from Candida albicans on a approximately 2.9-kb XbaI genomic DNA fragment. The putative (IMH3) encodes protein of 521 amino acids with extensive sequence similarity to the dehydrogenases Saccharomyces cerevisiae and various other organisms. Like S. IMH3 characterized in genome sequencing project, open reading frame C. is interrupted by small intron (248 bp) typical exon-intron boundaries consensus branchpoint sequence. mRNAs are detected both yeast...
beta-Defensins are cationic antimicrobial peptides expressed in epithelia. They exhibit antibacterial, antifungal, and antiviral properties. Defensins a component of the innate immune response, it has been proposed that they have protective role oral cavity. Previous studies shown human beta-defensin 1 (hBD-1) is constitutively epithelial cells but expression varies between individuals. We tested hypothesis genetic variations defensin peptide may be associated with opportunistic infections....
ABSTRACT Fluconazole-resistant Candida albicans , a cause of recurrent oropharyngeal candidiasis in patients with human immunodeficiency virus infection, has recently emerged as receiving cancer chemotherapy and marrow transplantation (MT). In this study, we performed detailed molecular analyses series C. isolates from an MT patient who developed disseminated caused by azole-resistant strain 2 weeks after initiation fluconazole prophylaxis (K. A. Marr, T. White, J. H. vanBurik, R. Bowden,...