Fun(gi)omics: Advanced and Diverse Technologies to Explore Emerging Fungal Pathogens and Define Mechanisms of Antifungal Resistance

Abstract

The landscape of infectious fungal agents includes previously unidentified or rare pathogens with the potential to cause unprecedented casualties in biodiversity, food security, and human health. The influences of human activity, including the crisis of climate change, along with globalized transport, are underlying factors shaping fungal adaptation to increased temperature and expanded geographical regions. Furthermore, the emergence of novel antifungal-resistant strains linked to excessive use of antifungals (in the clinic) and fungicides (in the field) offers an additional challenge to protect major crop staples and control dangerous fungal outbreaks. Hence, the alarming frequency of fungal infections in medical and agricultural settings requires effective research to understand the virulent nature of fungal pathogens and improve the outcome of infection in susceptible hosts. Mycology-driven research has benefited from a contemporary and unified approach of omics technology, deepening the biological, biochemical, and biophysical understanding of these emerging fungal pathogens. Here, we review the current state-of-the-art multi-omics technologies, explore the power of data integration strategies, and highlight discovery-based revelations of globally important and taxonomically diverse fungal pathogens. This information provides new insight for emerging pathogens through an in-depth understanding of well-characterized fungi and provides alternative therapeutic strategies defined through novel findings of virulence, adaptation, and resistance.

Fungal–Metal Interactions: A Review of Toxicity and Homeostasis

“…The most popular omics utilizes bioinformatics to analyze fungal–metal interactions at a nucleotide and protein level, which can reveal novel genes and mutations. In genomics, the entirety of a genome is assessed and compared to others for similarities and differences that can contribute to an organism’s characteristics [ 302 , 303 ]. Transcriptomics relies on RNA sequencing to survey gene expression through fold-changes in transcripts and proteomics assess fold-change in subsequent proteins.…”

Untargeted and Targeted LC-MS/MS Based Metabolomics Study on In Vitro Culture of Phaeoacremonium Species

“…Only by elucidating unknown metabolites is it possible to biologically interpret complex systems, gaining insight into the chemical-ecology of pathogenic fungi. Assignment of the chemical structure to fungal unknown secondary metabolites could be beneficial for investigations that deal with fungal pathogenic behavior [65], host-pathogen interaction [66][67][68] or, more in general, that use multi-omics approaches [69]. Consequently, three isolates (Pm45; CBS 729.97; CBS 498.94), one for each of Phaeoacremonium species, were selected according to the toxicity severity score, multivariate statistical analysis and untargeted metabolic profile, to be grown in vitro in larger amounts (4 to 8 L), to achieve the isolation and chemical (by spectroscopic method) and biological characterization of the unknown secondary metabolites.…”

Unraveling Caspofungin Resistance in Cryptococcus neoformans

“…With such a perspective, we must recognize this excellent report by the research group of John C. Panepinto, additionally because of the contribution of posttranscriptional gene regulation in drug resistance phenotypes, which has hitherto remained largely unexplored in pathogenic fungi due to the substantial complexity of these cell processes. However, there is no need to argue that a better understanding of such complex regulatory networks may lead to the identification of key components that could be targeted by adjunctive therapies for improving the efficacies of currently available drugs ( 10 , 18 – 20 ).…”