Severe cases of coronavirus disease 2019 (COVID-19) managed in the intensive care unit are prone to complications, including secondary infections with opportunistic fungal pathogens. Systemic fungal co-infections in hospitalized COVID-19 patients may exacerbate COVID-19 disease severity, hamper treatment effectiveness and increase mortality. Here, we reiterate the role of fungal co-infections in exacerbating COVID-19 disease severity as well as highlight emerging trends related to fungal disease burden in COVID-19 patients. Furthermore, we provide perspectives on the risk factors for fungal co-infections in hospitalized COVID-19 patients and highlight the potential role of prolonged immunomodulatory treatments in driving fungal co-infections, including COVID-19-associated pulmonary aspergillosis (CAPA), COVID-19-associated candidiasis (CAC) and mucormycosis. We reiterate the need for early diagnosis of suspected COVID-19-associated systemic mycoses in the hospital setting.

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.

In this contribution, we report on the possibility that cryptococcal protease(s) could activate the SARS-CoV-2 spike (S) protein. The S protein is documented to have a unique four-amino-acid sequence (underlined, SPRRAR↓S) at the interface between the S1 and S2 sites, that serves as a cleavage site for the human protease, furin. We compared the biochemical efficiency of cryptococcal protease(s) and furin to mediate the proteolytic cleavage of the S1/S2 site in a fluorogenic peptide. We show that cryptococcal protease(s) processes this site in a manner comparable to the efficiency of furin (p > 0.581). We conclude the paper by discussing the impact of these findings in the context of a SARS-CoV-2 disease manifesting while there is an underlying cryptococcal infection.

The yeast Candida albicans exhibits multiple morphologies dependent on environmental cues. Candida albicans biofilms are frequently polymicrobial, enabling interspecies interaction through proximity and contact. The interaction between C. albicans and the bacterium, Pseudomonas aeruginosa, is antagonistic in vitro, with P. aeruginosa repressing the yeast-to-hyphal switch in C. albicans. Previous transcriptional analysis of C. albicans in polymicrobial biofilms with P. aeruginosa revealed upregulation of genes involved in regulation of morphology and biofilm formation, including SET3, a component of the Set3/Hos2 histone deacetylase complex (Set3C). This prompted the question regarding the involvement of SET3 in the interaction between C. albicans and P. aeruginosa, both in vitro and in vivo. We found that SET3 may influence early biofilm formation by C. albicans and the interaction between C. albicans and P. aeruginosa. In addition, although deletion of SET3 did not alter the morphology of C. albicans in the presence of P. aeruginosa, it did cause a reduction in virulence in a Caenorhabditis elegans infection model, even in the presence of P. aeruginosa.

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