Fungal Genomics in Respiratory Medicine: What, How and When?

Abstract

Respiratory infections caused by fungal pathogens present a growing global health concern and are a major cause of death in immunocompromised patients. Worryingly, coronavirus disease-19 (COVID-19) resulting in acute respiratory distress syndrome has been shown to predispose some patients to airborne fungal co-infections. These include secondary pulmonary aspergillosis and mucormycosis. Aspergillosis is most commonly caused by the fungal pathogen Aspergillus fumigatus and primarily treated using the triazole drug group, however in recent years, this fungus has been rapidly gaining resistance against these antifungals. This is of serious clinical concern as multi-azole resistant forms of aspergillosis have a higher risk of mortality when compared against azole-susceptible infections. With the increasing numbers of COVID-19 and other classes of immunocompromised patients, early diagnosis of fungal infections is critical to ensuring patient survival. However, time-limited diagnosis is difficult to achieve with current culture-based methods. Advances within fungal genomics have enabled molecular diagnostic methods to become a fast, reproducible, and cost-effective alternative for diagnosis of respiratory fungal pathogens and detection of antifungal resistance. Here, we describe what techniques are currently available within molecular diagnostics, how they work and when they have been used.

Tackling the emerging threat of antifungal resistance to human health

“…However, in contrast to antibacterial resistance, a standardized WGS typing method is not widely used for fungi because of their larger genome sizes, frequent sexual recombination and the lack of standardized bioinformatic pipelines. Improved knowledge of antifungal resistance determinants and species genomes would support the transition to a WGS-powered understanding of fungal AMR for several human fungal pathogens 72 . Towards this goal, the development of rapid genomic analysis has been key to understanding the international 73 and local-scale 74 transmission of C. auris including the emergence of multidrug-resistant variants.…”

Insights into the Profile of the Human Expiratory Microbiota and Its Associations with Indoor Microbiotas

“… 17 , 76 , 77 Other less abundant fungal genera, including Mortierella , Chaetomium , Curvelaria , Cryptococcus , Candida , Guehomyces , Phaeoacremonium , Myrothecium , Aspergillus , and Penicillium , have been found in the respiratory samples and are opportunistic pathogens for respiratory fungal infections. 77 , 78 …”

“…The dominant genus Fusarium serves as both a respiratory commensal and an opportunistic pathogen and has been reported in the BAL fluid samples from healthy subjects and diseased subjects. ,, Other less abundant fungal genera, including Mortierella, Chaetomium, Curvelaria, Cryptococcus, Candida, Guehomyces, Phaeoacremonium, Myrothecium, Aspergillus, and Penicillium, have been found in the respiratory samples and are opportunistic pathogens for respiratory fungal infections. , …”

“…17,76,77 Other less abundant fungal genera, including Mortierella, Chaetomium, Curvelaria, Cryptococcus, Candida, Guehomyces, Phaeoacremonium, Myrothecium, Aspergillus, and Penicillium, have been found in the respiratory samples and are opportunistic pathogens for respiratory fungal infections. 77,78 Assembly and Heterogeneity of EBC Microbiotas. Stochastic processes, for example, dispersal, birth, death, extinction, and immigration, play a role in the assembly of expiratory bacterial and fungal communities.…”

Distribution and Current State of Molecular Genetic Characterization in Pathogenic Free-Living Amoebae

“…[148], Klebsiella pneumoniae [149], Corynebacterium diphtheriae [150], Staphylococcus aureus [147,151], Enterococcus faecalis [147] and Mycobacterium tuberculosis [152]. Although this discipline is more developed in bacteria and now in viruses, we can find extensive reports on emerging fungal pathogens [153][154][155][156][157] describing antifungal resistance mechanisms or shared synteny among geographically diverse species. Finally, the pathogens we are interested in discussing are protozoa, specifically the FLA.…”