Background: Emerging fungal pathogens pose important threats to global public health. The World Health Organization has responded to the rising threat of traditionally neglected fungal infections by developing a Fungal Priority Pathogens List (FPPL). Taking the highest-ranked fungal pathogen in the FPPL,Cryptococcus neoformans, as a paradigm, we review progress made over the past two decades on its global burden, its clinical manifestation and management of cryptococcal infection, and its antifungal resistance. The purpose of this review is to drive research efforts to improve future diagnoses, therapies, and interventions associated with fungal infections.Methods: We first reviewed trends in the global burden of HIV-associated cryptococcal infection, mainly based on a series of systematic studies. We next conducted scoping reviews in accordance with the guidelines described in the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews using PubMed and ScienceDirect with the keywordCryptococcus neoformans to identify case reports of cryptococcal infections published since 2000. We then reviewed recent updates on the diagnosis and antifungal treatment of cryptococcal infections. Finally, we summarized knowledge regarding the resistance and tolerance ofC. neoformansto approved antifungal drugs.Results: There has been a general reduction in the estimated global burden of HIV-associated cryptococcal meningitis since 2009, probably due to improvements in highly active antiretroviral therapies. However, cryptococcal meningitis still accounts for 19% of AIDS-related deaths annually. The incidences of CM in Europe and North America and the Latin America region have increased by approximately two-fold since 2009, while other regions showed either reduced or stable numbers of cases. Unfortunately, diagnostic and treatment options for cryptococcal infections are limited, and emerging antifungal resistance exacerbates the public health burden.Conclusion: The rising threat ofC. neoformansis compounded by accumulating evidence for its ability to infect immunocompetent individuals and the emergence of antifungal-resistant variants. Emphasis should be placed on further understanding the mechanisms of pathogenicity and of antifungal resistance and tolerance. The development of novel management strategies through the identification of new drug targets and the discovery and optimization of new and existing diagnostics and therapeutics are key to reducing the health burden.

Cryptococcus neoformans is a ubiquitous environmental fungus and an opportunistic pathogen that causes fatal cryptococcal meningitis. Advances in genomics, genetics, and cellular and molecular biology of C. neoformans have dramatically improved our understanding of this important pathogen, rendering it a model organism to study eukaryotic biology and microbial pathogenesis. In light of recent progress, we describe in this review the life cycle of C. neoformans with a special emphasis on the regulation of the yeast-to-hypha transition and different modes of sexual reproduction, in addition to the impacts of the life cycle on cryptococcal populations and pathogenesis.

Bacterial biofilms possess distinct community properties that affect various aspects of our daily lives. In particular, biofilms exhibit increased tolerance to chemical disinfectants, antimicrobial agents, and host immune responses.

Mycotoxin cocontamination is a severe threat to health and economic security worldwide. The mycotoxins aflatoxin B₁ (AFB₁), zearalenone (ZEN), deoxynivalenol, T-2 toxin, fumonisin B₁, and ochratoxin A are of particular concern due to their substantial toxicity. Lac-W is a laccase with the unique property of degrading these six mycotoxins in the absence of redox mediators. Nevertheless, their degradation rates are low. This work aims to improve the ability of Lac-W to degrade these six mycotoxins and to elucidate its detoxification mechanism. Including redox mediators increased the Lac-W degradation efficiency drastically, and completely degraded AFB₁ and ZEN within one hour. Additionally, Lac-W-AS has good temperature, pH, and ions adaptability in ZEN degradation. Lac-W-AS reduced the ZEN toxicity because ZEN degradation products significantly restored the bioluminescence intensity of Vibrio fischeri. A Lac-W-AS-mediated oxidation product of ZEN was structurally characterized as 15-OH-ZEN by UHPLC-MS/MS. Linear sweep voltammetry showed that AS affected the potential of Lac-W and accelerated the oxidation of ZEN. Finally, the combination of mediators (acetosyringone and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonate)) improved the degradation rate of mycotoxins. This work highlights that the combination of Lac-W with mediators serves as a good candidate for degrading multi-mycotoxin contaminants in food and feedstuff.

Cellular differentiation is instructed by developmental regulators in coordination with chromatin remodeling complexes. Much information about their coordination comes from studies in the model ascomycetous yeasts. It is not clear, however, what kind of information that can be extrapolated to species of other phyla in Kingdom Fungi. In the basidiomycete Cryptococcus neoformans, the transcription factor Znf2 controls yeast-to-hypha differentiation. Through a forward genetic screen, we identified the basidiomycete-specific factor Brf1. We discovered Brf1 works together with Snf5 in the SWI/SNF chromatin remodeling complex in concert with existent Znf2 to execute cellular differentiation. We demonstrated that SWI/SNF assists Znf2 in opening the promoter regions of hyphal specific genes, including the ZNF2 gene itself. This complex also supports Znf2 to fully associate with its target regions. Importantly, our findings revealed key differences in composition and biological function of the SWI/SNF complex in the two major phyla of Kingdom Fungi.