Transcriptomic and genomic changes associated with radioadaptation in Exophiala dermatitidis

Malo, Mackenzie E.; Schultzhaus, Zachary; Frank, Connor; Romsdahl, Jillian; Wang, Zheng; Dadachova, Ekaterina

doi:10.1016/j.csbj.2020.12.013

Cited by 15 publications

(21 citation statements)

References 51 publications

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“…Noteworthy, when radioadapted strain of Exophiala dermatitidis and the non-radioadapted control strain were exposed to Polonium-210, a mostly transcriptomic rather than genomic response to radiation was observed in radioadapted strain. This suggests that strains previously exposed to irradiation respond to subsequent exposures in a unique way ( Malo et al, 2021 ). Based on the observations reported for E. dermatitidis , it is plausible that A. niger JSC-093350089 strain response to the ISS environment was also unique, as it was previously isolated from the ISS and likely radioadapted itself.…”

Section: Discussionmentioning

confidence: 99%

The International Space Station Environment Triggers Molecular Responses in Aspergillus niger

et al. 2022

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Due to immense phenotypic plasticity and adaptability, Aspergillus niger is a cosmopolitan fungus that thrives in versatile environments, including the International Space Station (ISS). This is the first report of genomic, proteomic, and metabolomic alterations observed in A. niger strain JSC-093350089 grown in a controlled experiment aboard the ISS. Whole-genome sequencing (WGS) revealed that ISS conditions, including microgravity and enhanced irradiation, triggered non-synonymous point mutations in specific regions, chromosomes VIII and XII of the JSC-093350089 genome when compared to the ground-grown control. Proteome analysis showed altered abundance of proteins involved in carbohydrate metabolism, stress response, and cellular amino acid and protein catabolic processes following growth aboard the ISS. Metabolome analysis further confirmed that space conditions altered molecular suite of ISS-grown A. niger JSC-093350089. After regrowing both strains on Earth, production of antioxidant—Pyranonigrin A was significantly induced in the ISS-flown, but not the ground control strain. In summary, the microgravity and enhanced irradiation triggered unique molecular responses in the A. niger JSC-093350089 suggesting adaptive responses.

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Section: Discussionmentioning

confidence: 99%

The International Space Station Environment Triggers Molecular Responses in Aspergillus niger

et al. 2022

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“…Previous sputum isolates revealed the presence of this uncommon fungi two years prior, indicating that it persisted in low concentrations before having the opportunity to dominate the lung microbiome. Because E. dermatitidis is relatively slow growing (Rath et al 1997;Sudhadham et al 2011;Malo et al 2021), it may be easily missed during routine clinical microbiological identification. To better understand the CF disease and the fungal infections associated with a long-term disease such as this one, it is important to consider testing for slow growing microorganisms such as black yeasts.…”

Section: Heterogeneous Phenotypes Observed In the E Dermatitidis Isol...mentioning

confidence: 99%

“…Triacetylfusarinine is used to facilitate hyphal growth under iron-depleted conditions (Schrettl et al 2007;Tyrrell and Callaghan 2016). The E. dermatitis locus (HMPREF1120_07636) depicts the non-ribosomal peptide synthase SidC necessary for siderophore synthesis (Zajc et al 2019;Malo et al 2021). Polymicrobial infections persist in the CF lung environment through production and scavenging of extracellular siderophores which aid microbes in competition for resources (Tyrrell and Callaghan 2016;Sass et al 2019;Yan et al 2022).…”

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confidence: 99%

In host evolution of Exophiala dermatitidis in cystic fibrosis lung micro-environment

Kurbessoian

Murante

Crocker

et al. 2022

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Individuals with cystic fibrosis (CF) are susceptible to chronic lung infections that lead to inflammation and irreversible lung damage. While most respiratory infections that occur in CF are caused by bacteria, some are dominated by fungi such as the slow-growing black yeast Exophiala dermatitidis. Here, we analyze isolates of E. dermatitidis cultured from two samples, collected from a single subject two years apart. One isolate genome was sequenced using long-read Nanopore technology as an in-population reference to use in comparative single nucleotide polymorphism (SNP) and insertion-deletion (INDEL) variant analyses of twenty-three isolates. We then used population genomics and phylo-genomics to compare the isolates to each other as well as the type strain E. dermatitidis NIH/UT8656. Within the CF lung population, three E. dermatitidis clades were detected, each with varying mutation rates. Overall, the isolates were highly similar suggesting that they were recently diverged. All isolates were MAT 1-1, which was consistent with their high relatedness and the absence of evidence for mating or recombination between isolates. Phylogenetic analysis grouped sets of isolates into clades that contained isolates from both early and late time points indicating there are multiple persistent lineages. Functional assessment of variants unique to each clade identified alleles in genes that encode transporters, cytochrome P450 oxidoreductases, iron acquisition and DNA repair processes. Consistent with the genomic heterogeneity, isolates showed some stable phenotype heterogeneity in melanin production, subtle differences in antifungal minimum inhibitory concentrations, growth on different substrates. The persistent population heterogeneity identified in lung-derived isolates is an important factor to consider in the study of chronic fungal infections, and the analysis of changes in fungal pathogens over time may provide important insights into the physiology of black yeasts and other slow-growing fungi in vivo.

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“…While the Exophiala species complex is large, a considerable number of studies have applied WGS to both environmental and clinical Exophiala isolates. Notably, a study produced in 2020 analysed both the genomes and transcriptomes of E. dermatitidis isolates, indicating that some strains of this species are able to alter their transcriptomes to cope with moderate stress, before returning to the original state [ 121 ]. This could provide a mechanism of adaptation to the human host.…”

Section: Fungal Respiratory Infectionsmentioning

confidence: 99%

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

2021

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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.

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Transcriptomic and genomic changes associated with radioadaptation in Exophiala dermatitidis

Cited by 15 publications

References 51 publications

The International Space Station Environment Triggers Molecular Responses in Aspergillus niger

The International Space Station Environment Triggers Molecular Responses in Aspergillus niger

In host evolution of Exophiala dermatitidis in cystic fibrosis lung micro-environment

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

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