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Repurposing the non-steroidal anti-inflammatory drug diflunisal as an adjunct therapy with amphotericin B against mucoralean fungi.
J Med Microbiol
November 2024
Department of Microbial Biotechnology, Panjab University, Chandigarh 160014, India.
Mucormycosis is an aggressive, angioinvasive infection associated with high morbidity and mortality. The disease remains difficult to treat, with limited available antifungal drugs. Consequently, there is an urgent need to develop alternate therapeutics against mucormycosis.
View Article and Find Full Text PDFIdentification, characterization, and structure of a tRNA splicing enzyme RNA 5'-OH kinase from the pathogenic fungi Mucorales.
RNA
November 2024
Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA
Fungal Trl1 is an essential tRNA splicing enzyme composed of C-terminal cyclic phosphodiesterase and central polynucleotide kinase end-healing domains that convert the 2',3'-cyclic-PO and 5'-OH ends of tRNA exons into the 3'-OH,2'-PO and 5'-PO termini required for sealing by an N-terminal ATP-dependent ligase domain. Trifunctional Trl1 enzymes are present in most human fungal pathogens and are untapped targets for antifungal drug discovery. Mucorales species, deemed high-priority human pathogens by WHO, elaborate a noncanonical tRNA splicing apparatus in which a stand-alone monofunctional RNA ligase enzyme joins 3'-OH,2'-PO and 5'-PO termini.
View Article and Find Full Text PDFComputational targeting of iron uptake proteins in Covid-19 induced mucormycosis to identify inhibitors via molecular dynamics, molecular mechanics and density function theory studies.
In Silico Pharmacol
September 2024
Department of Biotechnology, RV College of Engineering, Bangalore, 560059 India.
Article Synopsis
- * The study focused on identifying iron uptake proteins associated with the fungus and screened a library of over 15,000 compounds to find potential inhibitors that could disrupt fungal growth.
- * Six promising small molecules were found to have low toxicity and strong binding capabilities to these proteins, which could lead to the development of effective antifungal treatments against mucormycosis.
Epidemiology and prognostic factors of mucormycosis in France (2012-2022): a cross-sectional study nested in a prospective surveillance programme.
Lancet Reg Health Eur
October 2024
Institut Pasteur, Paris Cité University, National Reference Center for Invasives Mycoses and Antifungals, Mycology Department, Paris, France.
Article Synopsis
- Mucormycosis, a severe fungal infection highlighted by the WHO, was studied in France from 2012 to 2022, revealing significant trends in epidemiology and mortality factors.
- Out of 550 cases, key underlying conditions included hematological malignancies (65.1%), with pulmonary infections most common (52.4%) and substantial seasonal variations suggesting more cases in autumn.
- The study linked the rise in PCR diagnostic methods to improved patient outcomes, highlighting that age, ICU diagnosis, and hematological malignancies increased mortality, while diagnosis after 2015 and surgical interventions decreased it.
Fungal and bacterial species on biowaste workers' hands and inhalation zone, and potential airway deposition.
Waste Manag
June 2024
National Research Centre for the Working Environment, Lersø Parkallé 105, 2100 Copenhagen Ø, Denmark.
This study aims to investigate the microbiological working environment of biowaste workers, focusing on airborne fungal and bacterial species exposure, size distribution, and species on workers' hands. The research, conducted across six plants with 45 personal exposure assessments, revealed a total of 150 bacterial species and 47 fungal species on workers' hands, including 19 and 9 species classified in risk class 2 (RC2), respectively. Workers' exposure analysis identified 172 bacterial and 32 fungal species, with several in RC2.
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