Unlabelled: is a life-threatening fungal pathogen that is a causative agent for pulmonary infection and meningoencephalitis in both immunocompetent and immunodeficient individuals. Recent studies have elucidated the important function of the target of rapamycin (TOR) signaling pathway in the modulation of virulence factor production and pathogenicity in animal infection models. Herein, we discovered that Ypk1, a critical component of the TOR signaling pathway, acts as a critical modulator in fungal pathogenicity through post-translational modifications (PTMs).
View Article and Find Full Text PDFposes a threat to human health, but anticryptococcal therapy is hampered by the emergence of drug resistance, whose underlying mechanisms remain poorly understood. Herein, we discovered that Isw1, an imitation switch chromatin remodeling ATPase, functions as a master modulator of genes responsible for and multidrug resistance in . Cells with the disrupted gene exhibited profound resistance to multiple antifungal drugs.
View Article and Find Full Text PDFSkin infections are major threats to human health, causing ∼500 incidences per 10 000 person-year. In patients with diabetes mellitus, particularly, skin infections are often accompanied by a slow healing process, amputation, and even death. Timely diagnosis of skin infection strains and on-site therapy are vital in human health and safety.
View Article and Find Full Text PDFIt is now understood that genes and their various mutations are associated with the onset and progression of diseases. However, routine genetic testing techniques are limited by their high cost, time consumption, susceptibility to contamination, complex operation, and data analysis difficulties, rendering them unsuitable for genotype screening in many cases. Therefore, there is an urgent need to develop a rapid, sensitive, user-friendly, and cost-effective method for genotype screening and analysis.
View Article and Find Full Text PDFMitochondrial quality control prevents accumulation of intramitochondrial-derived reactive oxygen species (mtROS), thereby protecting cells against DNA damage, genome instability, and programmed cell death. However, underlying mechanisms are incompletely understood, particularly in fungal species. Here, we show that Cryptococcus neoformans heat shock factor 3 (CnHsf3) exhibits an atypical function in regulating mtROS independent of the unfolded protein response.
View Article and Find Full Text PDFCryptococcal meningoencephalitis (CM) is emerging as an infection in HIV/AIDS patients shifted from primarily ART-naive to ART-experienced individuals, as well as patients with COVID-19 and immunocompetent hosts. This fungal infection is mainly caused by the opportunistic human pathogen . Brain or central nervous system (CNS) dissemination is the deadliest process for this disease; however, mechanisms underlying this process have yet to be elucidated.
View Article and Find Full Text PDFFront Cell Infect Microbiol
December 2021
Prevalence of fungal diseases has increased globally in recent years, which often associated with increased immunocompromised patients, aging populations, and the novel Coronavirus pandemic. Furthermore, due to the limitation of available antifungal agents mortality and morbidity rates of invasion fungal disease remain stubbornly high, and the emergence of multidrug-resistant fungi exacerbates the problem. Fungal pathogenicity and interactions between fungi and host have been the focus of many studies, as a result, lots of pathogenic mechanisms and fungal virulence factors have been identified.
View Article and Find Full Text PDFFront Cell Infect Microbiol
October 2021
is an invasive human fungal pathogen that causes more than 181,000 deaths each year. Studies have demonstrated that pulmonary infection induces innate immune responses involving copper, and copper detoxification in improves its fitness and pathogenicity during pulmonary infection. However, the molecular mechanism by which copper inhibits proliferation is unclear.
View Article and Find Full Text PDFBackground: Candida pelliculosa is an ecological fungal species that can cause infections in immunocompromised individuals. Numerous studies globally have shown that C. pelliculosa infects neonates.
View Article and Find Full Text PDFSpectrochim Acta A Mol Biomol Spectrosc
November 2021
Cryptococcus neoformans (C. neoformans) is a causative agent for acute pulmonary infection, which can further develop to lethal meningoencephalitis if untreated. The meningoencephalitis infection can be prevented, if timely treatment on pulmonary cryptococcal infection can be implemented based on its early diagnosis and accurate assessment.
View Article and Find Full Text PDFis a causative agent for pulmonary infection and meningoencephalitis. Understanding the host's response to infection is critical for developing effective treatment. Even though some have elucidated the host response at the transcriptome level, little is known about how it modulates its defense machinery through the proteome mechanism or how protein posttranslational modification responds to the infection.
View Article and Find Full Text PDFPathogens and hosts require rapid modulation of virulence and defense mechanisms at the infection axis, but monitoring such modulations is challenging. In studying the human fungal pathogen Cryptococcus neoformans, mouse and rabbit infection models are often employed to shed light on the disease mechanisms but that may not be clinically relevant. In this study, we developed an animal infection model using the non-human primate cynomolgus monkey Macaca fascicularis.
View Article and Find Full Text PDFLysine acetylation is critical in regulating important biological processes in many organisms, yet little is known about acetylome evolution and its contribution to phenotypic diversity. Here, we compare the acetylomes of baker's yeast and the three deadliest human fungal pathogens, , , and . Using mass spectrometry enriched for acetylated peptides together with public data from , we show that fungal acetylomes are characterized by dramatic evolutionary dynamics and limited conservation in core biological processes.
View Article and Find Full Text PDFInt J Mol Sci
January 2019
Copper is an essential trace element participating in many vital biological processes, however it becomes a toxic agent when in excess. Thus, precise and tight regulation of copper homeostasis processes, including transport, delivery, storage, detoxification, and efflux machineries, is important, ensuring that only the amount needed to sustain basic biological functions and simultaneously prevent copper toxicity in the cell is maintained. Numerous exciting studies have revealed that copper plays an indispensable role at the microbial pathogen-host axis for entities ranging from pathogenic bacteria to deadly fungal species.
View Article and Find Full Text PDFThe molecular mechanisms whereby CD8 T cells become "exhausted" in the tumor microenvironment remain unclear. Programmed death ligand-1 (PD-L1) is upregulated on tumor cells and PD-1-PD-L1 blockade has significant efficacy in human tumors; however, most patients do not respond, suggesting additional mechanisms underlying T cell exhaustion. B7 superfamily member 1 (B7S1), also called B7-H4, B7x, or VTCN1, negatively regulates T cell activation.
View Article and Find Full Text PDFChromatin conformation plays a key role in regulating gene expression and controlling cell differentiation. However, the whole-genome chromatin conformation changes that occur during leukemia cell differentiation are poorly understood. Here, we characterized the changes in chromatin conformation, histone states, chromatin accessibility, and gene expression using an all-trans retinoic acid (ATRA)-induced HL-60 cell differentiation model.
View Article and Find Full Text PDFCryptococcus neoformans is an important opportunistic fungal pathogen in humans. Recent studies have demonstrated that metals are critical factors for the regulation of fungal virulence in hosts. In this study, we systemically investigated the function of C.
View Article and Find Full Text PDFIn human cells, DNA is hierarchically organized and assembled with histones and DNA-binding proteins in three dimensions. Chromatin interactions play important roles in genome architecture and gene regulation, including robustness in the developmental stages and flexibility during the cell cycle. Here we propose in situ Hi-C method named Bridge Linker-Hi-C (BL-Hi-C) for capturing structural and regulatory chromatin interactions by restriction enzyme targeting and two-step proximity ligation.
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