MAIN TEXT: In this review, we discuss alternative carbon metabolism as a metabolic adaptation strategy for the pathogenesis of C. glabrata. As the glyoxylate cycle is an important pathway in the utilization of alternative carbon sources, we also highlight the key metabolic enzymes in the glyoxylate cycle and its necessity for the pathogenesis of C. glabrata. Finally, we explore the transcriptional regulatory network of the glyoxylate cycle.
CONCLUSION: Considering evidence from Candida albicans and Saccharomyces cerevisiae, this review summarizes the current knowledge of the glyoxylate cycle as an alternative carbon metabolic pathway of C. glabrata.
MATERIALS AND METHODS: Hsp90 was extracted using glass beads and ultracentrifugation from yeast cells and purified by ion exchange chromatography (DEAE-cellulose) and followed by affinity chromatography (hydroxyapatite). Purity of Hsp90 was controlled by SDS-PAGE and its identification was realized by immunoblotting test.
RESULTS: The graphs of ion exchange and affinity chromatography showed one peak in all C. albicans isolates obtained from both Malaysian and Iranian samples, infected mice and under high-thermal (42°C) and low-thermal (25°C) shock. In immunoblotting, the location of Hsp90 fragments was obtained around 47, 75 and 82kDa. The least average concentration ratios of Hsp90 were 0.350 and 0.240mg/g for Malaysian and Iranian isolates at 25°C, respectively, while the highest average concentration ratios of Hsp90 were 3.05 and 2.600mg/g for Malaysian and Iranian isolates at 42°C, respectively. There were differences in the ratio amount of Hsp90 between Malaysian isolates (1.01±0.07mg/g) and mice kidneys (1.23±0.28mg/g) as well as between Iranian isolates (0.70±0.19mg/g) and mice kidneys (1.00±0.28mg/g) (P<0.05).
CONCLUSION: The results showed differences in all situations tested including Iranian and Malaysian isolates, samples treated with temperatures (25°C or 42°C) and before and after infecting the mice (37°C), indicating higher virulent nature of this yeast species in high temperature in human and animal models.
PATIENT CONCERNS: A 64-year-old man with underlying well controlled diabetes mellitus was treated with 2 weeks' course of intravenous antifungal fluconazole for pyelonephritis as his blood culture grew Candida albicans. Concurrently, he complained of 3 months of bilateral painless progressive blurring of vision. At presentation, his visual acuity (VA) was light perception both eyes. Ocular examination revealed non granulomatous inflammation with dense vitritis of both eyes.
DIAGNOSIS: He was diagnosed with EFE but the condition responded poorly with the medications.
INTERVENTIONS: He was treated with intravitreal (IVT) amphotericin B and fluconazole was continued. Vitrectomy was performed and intraoperative findings included bilateral fungal balls in the vitreous and retina with foveal traction in the left eye. Postoperatively, vision acuity was 6/24, N8 right eye and 2/60, N unable for left eye with extensive left macular scar and hole. Vitreous cultures were negative. He received multiple IVT amphotericin B and was started on topical steroid eye drops for persistent panuveitis with systemic fluconazole. Ocular improvement was seen after switching to IVT and topical voriconazole. Despite this, his ocular condition deteriorated and he developed neovascular glaucoma requiring 3 topical antiglaucoma agents. Panretinal photocoagulation was subsequently performed.
OUTCOMES: At 3 months' follow-up, his vision acuity remained at 6/24 for right eye and 2/60 for the left eye. There was no recurrence of inflammation or infection in both eyes.
LESSONS: Voriconazole could serve as a promising broad spectrum tri-azole agent in cases of failure in first-line treatment or drug-resistant fungus.