Although Candida albicans remains the main cause of candidiasis, in recent years a significant number of infections has been attributed to non-albicans Candida (NAC) species, including Candida krusei. This epidemiological change can be partly explained by the increased resistance of NAC species to antifungal drugs. C. krusei is a diploid, dimorphic ascomycetous yeast that inhabits the mucosal membrane of healthy individuals. However, this yeast can cause life-threatening infections in immunocompromised patients, with hematologic malignancy patients and those using prolonged azole prophylaxis being at higher risk. Fungal infections are usually treated with five major classes of antifungal agents which include azoles, echinocandins, polyenes, allylamines, and nucleoside analogues. Fluconazole, an azole, is the most commonly used antifungal drug due to its low host toxicity, high water solubility, and high bioavailability. However, C. krusei possesses intrinsic resistance to this drug while also rapidly developing acquired resistance to other antifungal drugs. The mechanisms of antifungal resistance of this yeast involve the alteration and overexpression of drug target, reduction in intracellular drug concentration and development of a bypass pathway. Antifungal resistance menace coupled with the paucity of the antifungal arsenal as well as challenges involved in antifungal drug development, partly due to the eukaryotic nature of both fungi and humans, have left researchers to exploit alternative therapies. Here we briefly review our current knowledge of the biology, pathophysiology and epidemiology of a potential multidrug-resistant fungal pathogen, C. krusei, while also discussing the mechanisms of drug resistance of Candida species and alternative therapeutic approaches.

Just like the recent emergence of SARS-CoV-2 in December 2019 in Wuhan, a similar occurrence in the later part of the year 2002 also witnessed SARS infection that emerged in the Southern China ABSTRACT The emergence of the novel β-coronavirus (SARS-CoV-2) and subsequent outbreak of COVID-19, is a global health challenge with no known treatment to date and has culminated in significant morbidity and mortality. This article highlights current understanding on SARS-CoV-2 based on the available scientific evidence on human coronavirus (HCoV) infections, which could offer novel insights and therapeutic targets for SARS-CoV-2, the causative agent of COVID-19. Specifically, the paper presents available phytotherapeutic evidence against pathogenic HCoVs with a view to identifying potent plant-derived antiviral agents that could be developed to aid the fight against coronaviruses and the current COVID-19. Evidently, elucidation of CoV integral proteins such as the spike protein, angiotensin-converting enzyme 2, 3C-like cysteine protease and papain-like protease, as good targets for drug developments has lent credence to the use of medicinal plants or their metabolites as prophylaxis or treatment interventions in CoV infections and holds promising ground for SARS-CoV-2. While some promising phytocompounds are currently under clinical trials for COVID-19, increased research into plants and in-depth characterization of their metabolites could reveal more interesting results that would benefit humanity in its fight against emerging and re-emerging viral infections including the current COVID-19. Overall, given the current body of evidence on the potential development of phytotherapeutics for COVID-19, fears need to be allayed while clinical trials continue. Conclusively, the lockdown and other preventive measures which have been implemented in most parts of the world should be humanely exercised and supported to ensure compliance and safety of lives.

The incidence of infections by non-albicans Candida species, including Candida krusei, is increasing. Candida krusei exhibits intrinsic resistance to fluconazole and rapidly develops acquired resistance to other antifungals. Moreover, this yeast can form biofilm with increased resistance. Hence, there is a need to develop novel therapeutic strategies to combat infections caused by this pathogen. One such approach is through combination therapy with natural compounds, such as polyunsaturated fatty acids (PUFAs). This study aims to investigate the effect of PUFAs on fluconazole susceptibility of C. krusei biofilms, as well as the conserved nature of these effects in the Caenorhabditis elegans infection model. C. krusei biofilms were exposed to various fatty acids as well as combinations of fluconazole and linoleic acid (LA) or gamma-linolenic acid (GLA). The effect of these treatments on biofilm formation, cell ultrastructure, membrane integrity, oxidative stress and efflux pump activity was evaluated. In addition, the ability of the PUFAs to prolong survival and reduce the fungal burden of infected C. elegans, in the absence and presence of fluconazole, was assessed. Two P|UFAs, LA and GLA had he displayed significant inhibition of C. krusei biofilms and both of them increased the susceptibility of C. krusei biofilm to fluconazole in vitro via induction of oxidative stress, cell membrane damage, and disruption of efflux pump activity. These PUFAs also extended the lifespan of infected nematodes and displayed a potentiating effect with fluconazole in this model. This may pave the way for future studies into novel antifungal drug targets and treatment options. Lay Abstract The pathogenic yeast, Candida krusei, is naturally resistant to the antifungal drug, fluconazole. This study finds that polyunsaturated fatty acids, linoleic and gamma-linolenic acid, can inhibit C. krusei and overcome this resistance of in vitro biofilms, as well as in a nematode infection model.

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