The eukaryotic fungal species Candida albicans is a critical infective pathogenic agent. The β-amino acid, Icofungipen, is an effective inhibitor of Candida albicans. Icofungipen binds at the active site of the isoleucyl tRNA synthetase (IleRS) from Candida albicans (CaIleRS) and halts protein translation in fungus. In the present work, we have investigated the mechanism of binding of Icogungipen (abbreviated as IFP). Molecular dynamics (MD) simulations show that the carboxylic acid group of IFP in the CaIleRS: IFP complex is more oriented towards the Connective Polypeptide (CP) core loop compared to the carboxylic acid group of Ile in the CaIleRS: Ile complex. The Arg 410 of the CP core loop near the substrate is extended towards the IFP. Due to the difference in the conformation of residues of the CP core loop, the KMSKR loop is more proximal to the CP core loop in CaIleRS: IFP. The editing domain which is covalently linked with the CP core loop in the CaIleRS: IFP complex is also oriented in such a way that the active site cavity is narrow and longer. The metadynamics calculation shows that the IFP is trapped in a deeper potential well compared to Ile which is due to the effective closure of the gateway of the active site by KMSKR and CP core loop. The thin, long shape of the active site and the closed gate of the active site in CaIleRS: IFP complex is responsible for the effective capture of IFP relative to Ile in the active site.Communicated by Ramaswamy H. Sarma.

To evaluate the efficacy and safety of hypochlorous acid (HOCI) eye drops in the treatment of fungal keratitis.
A total of 96 patients (96 eyes) with fungal keratitis were randomly divided into two groups: group Ι (conventional treatment + topical HOCI eye drops); The group II (conventional treatment). According to its severity, those patients were divided into grade Ι or grade II. Use of fungal scraping and culture to identify the type of fungal infection, slit lamp examination, and corneal fluorescein staining to observe regression, and confocal corneal microscopy to assess fungal mycelial changes. The main outcome measures were the success rate, healing time, visual recovery, and complications. The Kaplan-Meier curve method was used to analysis of the survival function of days to cure between the two groups.
There were no statistical differences between the two groups in terms of general condition, medical history, and grading. Corneal scraping results showed that all patients had filamentous fungi. For grade Ι patients, all patients were cured, and the patients in Group I showed faster healing speed than that in Group II (t = -3.665, p < .01). For grade II patients, the recovery time (t = -4.121, p < .01) and the disappearance of hypopyon (t = -4.291, p < .01) were significantly faster in the combination group. In grade Ι and II patients, the final visual acuity and the incidence of complications such as corneal neovascularization, cataract, and hyphema showed no differences in both groups. The survival curve showed that the healing rate of ulcers in the combination treatment group was faster than that in the conventional treatment group (χ2 = 14.332, p = .001).
HOCI can accelerate the healing of fungal keratitis without obvious complications, indicating a promising future in the field of keratitis treatment.

UNASSIGNED: Azole antifungals are the most commonly used antifungals. The high use of azoles for long-term therapy and prophylaxis is prone to cause resistance. Thus, it is necessary to evaluate the antifungal activity against Candida albicans.
UNASSIGNED: Analyzing the comparison of antifungal exposure on the time-kill curve to Candida albicans.
UNASSIGNED: A case-control study was conducted with a posttest control group design. This study used Candida albicans clinical and ATCC isolates exposed to antifungal solutions with 1 ×, 4 ×, and 16 × minimum inhibitory concentrations (MIC). Antibiotics used included fluconazole, itraconazole, and voriconazole. Candida albicans isolates were incubated with MIC, and the number of colonies was counted at 0, 2, 4, 8, 12, 24, and 48 h. The number of colonies that grew every hour of observation was included in the time-kill curve. The data were then analyzed using an ANOVA test with p <0.05.
UNASSIGNED: The antifungals (fluconazole, itraconazole, and voriconazole) showed fungistatic activity against Candida albicans clinical and ATCC isolates. There was a significant comparison between the antifungal group and the control group at 12, 24, and 48 h. The most significant difference between antifungal and control group was found at 24 h where fluconazole had 95% CI = 0.807-2.061 (p <0.001), itraconazole 95% CI = 0.722-1.976 (p <0.001), and voriconazole CI 95% = 0.807-2.062 (p <0.001).
UNASSIGNED: Fluconazole, itraconazole, and voriconazole were effective in inhibiting the growth of Candida albicans. Maximum inhibition in vitro occurs after 12 h of antifungal exposure.

The two leading yeast pathogens of humans, Candida albicans and Cryptococcus neoformans, cause systemic infections in >1.4 million patients worldwide with mortality rates approaching 75%. It is thus imperative to study fungal virulence mechanisms, efficacy of antifungal drugs, and host response pathways. While this is commonly done in mammalian models, which are afflicted by ethical and practical concerns, invertebrate models, such as wax moth larvae and nematodes have been introduced over the last two decades. To complement existing invertebrate host models, we developed fifth instar caterpillars of the Tobacco Hornworm moth Manduca sexta as a novel host model. These caterpillars can be maintained at 37°C, are suitable for injections with defined amounts of yeast cells, and are susceptible to the most threatening yeast pathogens, including C. albicans, C. neoformans, C. auris, and C. glabrata. Importantly, fungal burden can be assessed daily throughout the course of infection in a single caterpillar\'s feces and hemolymph. Infected caterpillars can be rescued by treatment with antifungal drugs. Notably, these animals are large enough for weight to provide a reliable and reproducible measure of fungal disease and to facilitate host tissue-specific expression analyses. M. sexta caterpillars combine a suite of parameters that make them suitable for the study of fungal virulence.

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