A5007222260- Antifungal resistance and susceptibility
- Ocular Infections and Treatments
- Fungal and yeast genetics research
- Endoplasmic Reticulum Stress and Disease
- Ocular Surface and Contact Lens
- Mycotoxins in Agriculture and Food
- Fungal Infections and Studies
- Neurological diseases and metabolism
- Plant Pathogens and Fungal Diseases
- Microbial Metabolism and Applications
- Microbial Natural Products and Biosynthesis
- Heat shock proteins research
- Corneal surgery and disorders
- Fungal Biology and Applications
- Bacterial biofilms and quorum sensing
- Porphyrin Metabolism and Disorders
- Enzyme-mediated dye degradation
- Microbial Inactivation Methods
- CRISPR and Genetic Engineering
- Microbial infections and disease research
- Allergic Rhinitis and Sensitization
- RNA and protein synthesis mechanisms
- Studies on Chitinases and Chitosanases
- Signaling Pathways in Disease
- Mycorrhizal Fungi and Plant Interactions
University of Oklahoma Health Sciences Center
2019-2024
University of Pittsburgh
2024
Dartmouth College
2010-2016
University of Cincinnati Medical Center
2007-2012
Oncology Hematology Care
2012
Sabin Vaccine Institute
2007-2010
University of Cincinnati
2010
Scientific communication is facilitated by a data-driven, scientifically sound taxonomy that considers the end-user's needs and established successful practice. In 2013, Fusarium community voiced near unanimous support for concept of represented clade comprising all agriculturally clinically important species, including F. solani species complex (FSSC). Subsequently, this was challenged in 2015 one research group who proposed dividing genus into seven genera, FSSC described as members...
Filamentous fungi rely heavily on the secretory pathway, both for delivery of cell wall components to hyphal tip and production secretion extracellular hydrolytic enzymes needed support growth polymeric substrates. Increased demand system exerts stress endoplasmic reticulum (ER), which is countered by activation a coordinated response pathway termed unfolded protein (UPR). To determine contribution UPR virulence filamentous fungal pathogen Aspergillus fumigatus, we disrupted hacA gene,...
ABSTRACT Previous work has shown that environmental and clinical isolates of Aspergillus fumigatus represent a diverse population occupies variety niches, extensive genetic diversity, exhibits virulence heterogeneity in number animal models invasive pulmonary aspergillosis (IPA). However, mechanisms explaining differences among A. remain enigmatic. Here, we report significant difference two common lab strains, CEA10 AF293, the murine triamcinolone immunosuppression model IPA, which...
Abstract Fungal infections cause more than 1.5 million deaths a year. Due to emerging antifungal drug resistance, novel strategies are urgently needed combat life-threatening fungal diseases. Here, we identify the host defense peptide mimetic, brilacidin (BRI) as synergizer with caspofungin (CAS) against CAS-sensitive and CAS-resistant isolates of Aspergillus fumigatus, Candida albicans , C. auris CAS-intrinsically resistant Cryptococcus neoformans . BRI also potentiates azoles A. fumigatus...
Endoplasmic reticulum (ER) stress is a condition in which the protein folding capacity of ER becomes overwhelmed by an increased demand for secretion or exposure to compounds that disrupt homeostasis. In yeast and other fungi, accumulation unfolded proteins detected ER-transmembrane sensor IreA/Ire1, responds cleaving intron from downstream cytoplasmic mRNA HacA/Hac1, allowing translation transcription factor coordinates series adaptive responses are collectively known as response (UPR)....
ABSTRACT Autophagy is the major cellular pathway for bulk degradation of cytosolic material and required to maintain viability under starvation conditions. To determine contribution autophagy stress responses in filamentous fungus Aspergillus fumigatus , we disrupted A. atg1 gene, encoding a serine/threonine kinase autophagy. The ΔAf mutant showed abnormal conidiophore development reduced conidiation, but defect could be bypassed by increasing nitrogen content medium. When transferred...
The genome of Aspergillus fumigatus encodes two isoforms the catalytic subunit cAMP-dependent Protein Kinase (PKA). Although deletion class I isoform, pkaC1, leads to an attenuation virulence, function II subunit, PkaC2, was previously uninvestigated. In this report, we demonstrate that both act in concert support various physiologic processes promote virulence pathogen. Whereas pkaC1 and pkaC2 single-deletion mutants display wild-type conidial germination, a double-deletion mutant is...
Fungal diseases affect millions of humans annually, yet fungal pathogens remain understudied. The mold Aspergillus flavus can cause both aspergillosis and keratitis infections, but closely related species are not considered clinically relevant. To study the evolution A. pathogenicity, we examined genomic phenotypic traits two strains three species, arachidicola (two strains), parasiticus nomiae (one strain). We identified >3,000 orthologous proteins unique to flavus, including seven...
ABSTRACT The Ras family of proteins is a large group monomeric GTPases. Members the fungal act as molecular switches that transduce signals from outside cell to signaling cascades inside cell. A. fumigatus RasA 94% identical essential gene Aspergillus nidulans and member sharing highest identity homologs studied in many other fungi. In this study, we report rasA not , but its absence associated with slowed germination severe defect radial growth. Δ hyphae were more than two times diameter...
The poor visual outcomes associated with fungal keratitis (FK) underscore a need to identify pathways that can serve as novel antifungal targets. In this report, we investigated whether hypoxia develops in the FK cornea and, by extension, if adaptation is essential for virulence setting.
Fungal keratitis (FK) is a site-threatening infection of the cornea associated with ocular trauma and contact lens wear. Members Fusarium solani species complex (FSSC) are predominant agents FK worldwide, but genes that support their corneal virulence poorly understood. As means to bolster genetic analysis in FSSC pathogens, we sought employ CRISPR/Cas9 system an isolate identified as petroliphilum. Briefly, this approach involves introduction two components into fungal protoplasts: (1) A...
Summary Fungal infections, a leading cause of mortality among eukaryotic pathogens, pose growing global health threat due to the rise drug-resistant strains. New therapeutic strategies are urgently needed combat this challenge. The PCA pathway for biosynthesis Co-enzyme A (CoA) and Acetyl-CoA (AcCoA) from vitamin B5 (pantothenic acid) has been validated as an excellent target development new antimicrobials against fungi protozoa. regulates key cellular processes including metabolism fatty...
The Aspergillus fumigatus unfolded protein response (UPR) is a two-component relay consisting of the ER-bound IreA protein, which splices and activates mRNA transcription factor HacA. Spliced hacA accumulates under conditions acute ER stress in vitro , UPR null mutants are hypovirulent murine model invasive pulmonary infection. In this report, we demonstrate that deletion mutant ( ΔhacA ) furthermore avirulent fungal keratitis, corneal infection, an important cause ocular morbidity...
ABSTRACT Proper regulation of the cyclic AMP-dependent protein kinase (PKA) pathway is required for normal growth and development in many fungi. We have reported that deletion PKA regulatory subunit gene, pkaR , Aspergillus fumigatus leads to defects germination a hypersensitivity conidia oxidative stress. In this study, we further analyzed Δ found large proportion were abnormally larger than wild type. Because swelling increased susceptibility stress are characteristic germinating conidia,...
Ocular glands play a critical role in eye health through the secretion of factors directly onto ocular surface. The cornea is normally transparent tissue necessary for visual acuity located anterior segment eye. Corneal damage can occur during microbial infection cornea, resulting potentially permanent deficits. involvement corneal has been only briefly described. We hypothesized that contribute to resistance as an arm eye-associated lymphoid and may also be susceptible secondary keratitis....
Fungal keratitis (FK) pathology is driven by both fungal growth and inflammation within the corneal stroma. Standard in vitro infection models ̶ involving co-culture of pathogen cells tissue culture medium are sufficient to probe host responses fungus; however, they lack physiological structure nutrient composition stroma accurately study invasiveness metabolic processes. We therefore sought develop a model FK that would allow for cell biology be evaluated parallel. Towards this end, we...
Abstract Objective The fungal unfolded protein response consists of a two-component relay in which the ER-bound sensor, IreA, splices and activates mRNA transcription factor, HacA. Previously, we demonstrated that hacA is essential for Aspergillus fumigatus virulence murine model keratitis (FK), suggesting pathway could serve as therapeutic target. Here investigate antifungal properties known inhibitors mammalian Ire1 both vitro treatment FK. Methods activity was tested against conidia...
Objective The fungal unfolded protein response consists of a two-component relay in which the ER-bound sensor, IreA, splices and activates mRNA transcription factor, HacA. Previously, we demonstrated that hacA is essential for Aspergillus fumigatus virulence murine model keratitis (FK), suggesting pathway could serve as therapeutic target. Here investigate antifungal properties known inhibitors mammalian Ire1 both vitro treatment FK. Methods activity was tested against conidia several A....
ABSTRACT The Aspergillus fumigatus unfolded protein response (UPR) is a two-component relay consisting of the ER-bound IreA protein, which splices and activates mRNA transcription factor HacA. Spliced hacA accumulates under conditions acute ER stress in vitro , UPR null mutants are hypovirulent murine model invasive pulmonary infection. In this report, we demonstrate that deletion mutant completely unable to establish infection fungal keratitis, corneal an important cause ocular morbidity...
Abstract Purpose: The poor visual outcomes associated with fungal keratitis (FK) underscore a need to identify pathways that can serve as novel antifungal targets. In this report, we investigated whether hypoxia develops in the FK cornea and, by extension, if adaptation is essential for virulence setting. Methods: C57BL/6j mice were inoculated Aspergillus fumigatus and Fusarium solani var petroliphilum via topical overlay or instrastromal injection. At various time points post-inoculation...
SUMMARY Fungal infections, a leading cause of mortality among eukaryotic pathogens, pose growing global health threat due to the rise drug-resistant strains. New therapeutic strategies are urgently needed combat this challenge. The PCA pathway for biosynthesis Co-enzyme A (CoA) and Acetyl-CoA (AcCoA) from vitamin B5 (pantothenic acid) has been validated as an excellent target development new antimicrobials against fungi protozoa. regulates key cellular processes including metabolism fatty...