A5060438205- Ocular Infections and Treatments
- Antifungal resistance and susceptibility
- Neurological diseases and metabolism
- Microbial Metabolism and Applications
- Microbial Natural Products and Biosynthesis
- Endoplasmic Reticulum Stress and Disease
- Heat shock proteins research
- Bacterial biofilms and quorum sensing
- Ocular Surface and Contact Lens
- Antimicrobial Peptides and Activities
- Fungal Infections and Studies
- Mycotoxins in Agriculture and Food
- RNA and protein synthesis mechanisms
- Porphyrin Metabolism and Disorders
- Signaling Pathways in Disease
- Biochemical and Molecular Research
University of Oklahoma Health Sciences Center
2022-2024
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...
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...
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.
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 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...
Fungal infections affect over one billion people worldwide each year and are the leading cause of mortality by eukaryotic pathogens with an estimated 150 million severe life-threatening cases 1.7 deaths reported annually. The rapid increase in number clinical emergence multidrug resistant such as Candida auris emphasize urgent need for new strategies to develop more effective, selective safe antifungals. Coenzyme A (CoA) plays a central role key cellular processes including citric acid...
ABSTRACT Fungal diseases affect millions of humans annually, yet fungal pathogens remain understudied. The mold Aspergillus flavus is a causative agent both aspergillosis and keratitis infections, but species closely related to A. are not considered clinically relevant. To study the evolution pathogenicity, we examined genomic phenotypic traits two strains three non- pathogenic species: arachidicola (two strains), parasiticus nomiae (one strain). We identified over 3,000 orthologous proteins...