A phylogenetic approach to explore the Aspergillus fumigatus conidial surface-associated proteome and its role in pathogenesis DOI Creative Commons
Gustavo H. Goldman, Clara Valero, Camila Figueiredo Pinzan

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 18, 2023

, an important pulmonary fungal pathogen causing several diseases collectively called aspergillosis, relies on asexual spores (conidia) for initiating host infection. Here, we used a phylogenomic approach to compare proteins in the conidial surface of

Language: Английский

Recent developments in Aspergillus fumigatus research: diversity, drugs, and disease DOI
Nicole Kordana, Angus Johnson, Karen Quinn

et al.

Microbiology and Molecular Biology Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 10, 2025

SUMMARY Advances in modern medical therapies for many previously intractable human diseases have improved patient outcomes. However, successful disease treatment outcomes are often prevented due to invasive fungal infections caused by the environmental mold Aspergillus fumigatus . As contemporary antifungal not experienced same robust advances as other therapies, defining mechanisms of A. initiation and progression remains a critical research priority. To this end, World Health Organization recently identified priority pathogen Centers Disease Control has highlighted emergence triazole-resistant isolates. The expansion diversity host populations susceptible aspergillosis complex dynamic genotypic phenotypic call reinvigorated assessment pathobiological drug-susceptibility mechanisms. Here, we summarize recent advancements field discuss challenges our understanding heterogeneity its pathogenesis diverse populations.

Language: Английский

Citations

1
Giant transposons promote strain heterogeneity in a major fungal pathogen DOI Creative Commons
Emile Gluck‐Thaler, Adrian Forsythe, Charles Puerner

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 28, 2024

Fungal infections are difficult to prevent and treat in large part due strain heterogeneity. However, the genetic mechanisms driving pathogen variation remain poorly understood. Here, we determined extent which

Language: Английский

Citations

5
Aspergillus fumigatus conidial surface-associated proteome reveals factors for fungal evasion and host immunity modulation DOI
Camila Figueiredo Pinzan, Clara Valero, Patrícia Alves de Castro

et al.

Nature Microbiology, Journal Year: 2024, Volume and Issue: 9(10), P. 2710 - 2726

Published: Aug. 27, 2024

Language: Английский

Citations

5
Evolutionary origin and population diversity of a cryptic hybrid pathogen DOI Creative Commons
Jacob L. Steenwyk,

S E Knowles,

Rafael Wesley Bastos

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Sept. 28, 2024

Language: Английский

Citations

5
Genetic Diversity of Human Fungal Pathogens DOI
Jillian Freese, Sinem Beyhan

Current Clinical Microbiology Reports, Journal Year: 2023, Volume and Issue: 10(2), P. 17 - 28

Published: Feb. 14, 2023

Language: Английский

Citations

10
Leading developments in basic research on aspergillosis and mucormycosis DOI Creative Commons

Argha Sarkar,

Drauzio E.N. Rangel, Nir Osherov

et al.

Fungal Biology, Journal Year: 2025, Volume and Issue: unknown, P. 101574 - 101574

Published: April 1, 2025

Language: Английский

Citations

0
Giant transposons promote strain heterogeneity in a major fungal pathogen DOI Creative Commons
Emile Gluck‐Thaler, Adrian Forsythe, Charles Puerner

et al.

mBio, Journal Year: 2025, Volume and Issue: unknown

Published: May 12, 2025

ABSTRACT Fungal infections are difficult to prevent and treat in large part due strain heterogeneity, which confounds diagnostic predictability. Yet, the genetic mechanisms driving strain-to-strain variation remain poorly understood. Here, we determined extent Starships —giant transposons capable of mobilizing numerous fungal genes—generate phenotypic variability opportunistic human pathogen Aspergillus fumigatus . We analyzed 519 diverse strains, including 11 newly sequenced with long-read technology multiple isolates same reference strain, reveal 20 distinct that generating genomic heterogeneity over timescales relevant for experimental reproducibility. Starship -mobilized genes encode functions, known biofilm-related virulence factors biosynthetic gene clusters, many differentially expressed during infection antifungal exposure a strain-specific manner. These findings support new model evolution wherein help generate genome structure, content, expression among strains. Together, our results demonstrate previously hidden mechanism genotypic and, turn, major pathogen. IMPORTANCE No “one size fits all” option exists treating Accounting is thus fundamental developing efficacious treatments strategies safeguarding health. report significant progress toward achieving this goal by uncovering : giant transposons, called , span dozens kilobases mobilize as cargo. By conducting systematic investigation these unusual single species, their contributions population-level at genome, pangenome, transcriptome levels. The compendium develop will not only predict introduced elements laboratory experiments but serve foundational resource determining how impact clinically phenotypes, such resistance pathogenicity.

Language: Английский

Citations

0
Evolutionary origin, population diversity, and diagnostics for a cryptic hybrid pathogen DOI Creative Commons
Jacob L. Steenwyk,

S E Knowles,

Rafael Wesley Bastos

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: July 3, 2023

Cryptic fungal pathogens pose significant identification and disease management challenges due to their morphological resemblance known pathogenic species while harboring genetic (often) infectionrelevant trait differences. The cryptic pathogen

Language: Английский

Citations

9
COVID-19-Associated Pulmonary Aspergillosis Isolates Are Genomically Diverse but Similar to Each Other in Their Responses to Infection-Relevant Stresses DOI Creative Commons
Matthew E. Mead, Patrícia Alves de Castro, Jacob L. Steenwyk

et al.

Microbiology Spectrum, Journal Year: 2023, Volume and Issue: 11(2)

Published: March 22, 2023

Secondary infections caused by the pulmonary fungal pathogen Aspergillus fumigatus are a significant cause of mortality in patients with severe coronavirus disease 19 (COVID-19). Even though epithelial cell damage and aberrant cytokine responses have been linked to susceptibility COVID-19-associated aspergillosis (CAPA), little is known about mechanisms underpinning copathogenicity. Here, we analyzed genomes 11 A. isolates from CAPA three centers different European countries. did not cluster based on geographic origin genome-scale phylogeny representative isolates. Phenotypically, were more similar A1160 reference strain than Af293 when grown infection-relevant stresses, except for interactions human immune cells wherein macrophage those induced strain. Collectively, our data indicate that genomically diverse but each other their stresses. A larger number should be studied better understand molecular epidemiology identify genetic drivers copathogenicity antifungal resistance COVID-19.

Language: Английский

Citations

5
The fungal expel of 5-fluorocytosine derived fluoropyrimidines mitigates its antifungal activity and generates a cytotoxic environment DOI Creative Commons
Luis Enrique Sastré-Velásquez,

Alex Dallemulle,

Alexander Kühbacher

et al.

PLoS Pathogens, Journal Year: 2022, Volume and Issue: 18(12), P. e1011066 - e1011066

Published: Dec. 27, 2022

Invasive aspergillosis remains one of the most devastating fungal diseases and is predominantly linked to infections caused by opportunistic human mold pathogen Aspergillus fumigatus. Major treatment regimens for disease comprise administration antifungals belonging azole, polyene echinocandin drug class. The prodrug 5-fluorocytosine (5FC), which only representative a fourth class, nucleobase analogs, shows unsatisfactory in vitro activities barely used aspergillosis. main route 5FC activation A. fumigatus comprises its deamination into 5-fluorouracil (5FU) FcyA, followed Uprt-mediated 5FU phosphoribosylation 5-fluorouridine monophosphate (5FUMP). In this study, we characterized examined role metabolic bypass that generates nucleotide via (5FUR) through uridine phosphorylase kinase activities. Resistance profiling mutants lacking distinct pyrimidine salvage suggested minor contribution alternative 5FUMP formation. We further analyzed efflux tolerance found cells exposed reduce intracellular fluoropyrimidine levels their export environment. This release, was particularly high Uprt, toxic environment cytosine deaminase as well mammalian cells. Employing broad-spectrum pump inhibitor clorgyline, demonstrate synergistic properties compound combination with 5FC, 5FUR.

Language: Английский

Citations

7