Publications by authors named "Jorge D Lightfoot"

Fungal keratitis is a severe corneal infection most commonly caused by filamentous fungi. Even with prompt treatment with current antifungals, it often results in corneal perforation and blindness. In this report, we observe that the beta-adrenergic antagonist, propranolol, displays antifungal activity against and corneal isolates o and strikingly blocks disease establishment in a murine model of keratitis.

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Objective: The fungal unfolded protein response consists of a two-component relay in which the ER-bound sensor, IreA, splices and activates the mRNA of the transcription factor, HacA. Previously, we demonstrated that is essential for virulence in a murine model of fungal keratitis (FK), suggesting the pathway could serve as a therapeutic target. Here we investigate the antifungal properties of known inhibitors of the mammalian Ire1 protein both and in a treatment model of FK.

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Objective: The fungal unfolded protein response consists of a two-component relay in which the ER-bound sensor, IreA, splices and activates the mRNA of the transcription factor, HacA. Previously, we demonstrated that is essential for virulence in a murine model of fungal keratitis (FK), suggesting the pathway could serve as a therapeutic target. Here we investigate the antifungal properties of known inhibitors of the mammalian Ire1 protein both and in a treatment model of FK.

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Article Synopsis
  • The study investigates the development of hypoxia in the cornea due to fungal keratitis and its impact on the virulence of fungi like Aspergillus fumigatus and Fusarium solani.
  • Researchers used C57BL/6J mice to evaluate tissue hypoxia through injections of pimonidazole, alongside genetic manipulation of A. fumigatus to understand the role of the srbA gene in virulence.
  • Findings indicate that corneal hypoxia occurs rapidly after fungal infection, and pathways like SrbA are crucial for fungi to establish infections, suggesting potential new targets for antifungal treatments.
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The Aspergillus fumigatus unfolded protein response (UPR) is a two-component relay consisting of the ER-bound IreA protein, which splices and activates the mRNA of the transcription factor HacA. Spliced hacA accumulates under conditions of acute ER stress in vitro, and UPR null mutants are hypovirulent in a murine model of invasive pulmonary infection. In this report, we demonstrate that a hacA deletion mutant (ΔhacA) is furthermore avirulent in a model of fungal keratitis, a corneal infection, and an important cause of ocular morbidity and unilateral blindness worldwide.

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Fungal infections cause more than 1.5 million deaths a year. Due to emerging antifungal drug resistance, novel strategies are urgently needed to combat life-threatening fungal diseases.

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Fungal diseases affect millions of humans annually, yet fungal pathogens remain understudied. The mold Aspergillus flavus can cause both aspergillosis and fungal keratitis infections, but closely related species are not considered clinically relevant. To study the evolution of A.

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Article Synopsis
  • Fungal infections are a major health threat, causing approximately 150 million severe cases and 1.7 million deaths yearly, highlighting the need for new antifungal drugs due to the rise of multidrug-resistant strains.
  • The PanK enzyme in fungi is crucial for utilizing pantothenic acid and is the first step in coenzyme A biosynthesis, with a single PanK gene present in sequenced fungi.
  • Researchers have determined the crystal structure of fungal PanK, identifying new inhibitors that could effectively target and inhibit the growth of Candida species, positioning PanK as a promising target for new antifungal treatments.
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Fungal keratitis (FK) is a site-threatening infection of the cornea associated with ocular trauma and contact lens wear. Members of the species complex (FSSC) are predominant agents of FK worldwide, but genes that support their corneal virulence are poorly understood. As a means to bolster genetic analysis in FSSC pathogens, we sought to employ a CRISPR/Cas9 system in an FK isolate identified as .

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