Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus

Nierman, William C.; Pain, Arnab; Anderson, Michael J.; Wortman, Jennifer; Kim, H. Stanley; Arroyo, Javier; Berriman, Matthew; Abe, Keietsu; Archer, David B.; Bermejo, Clara; Bennett, Joan W.; Bowyer, Paul; Chen, Dan; Collins, Matthew D.; Coulsen, Richard; Davies, Robert M.; Dyer, Paul S.; Farman, Mark L.; Fedorova, Nadia; Fedorova, Natalie D.; Feldblyum, Tamara; Fischer, Reinhard; Fosker, Nigel; Fraser, Audrey; Garcı́a, José Luis; García, María J.; Goble, Arlette; Goldman, Gustavo H.; Gomi, Katsuya; Griffith-Jones, Sam; Gwilliam, Ryan; Haas, Brian J.; Haas, Hubertus; Harris, David; Horiuchi, Hiroyuki; Huang, Jiaqi; Humphray, Sean; Jiménez, Javier; Keller, Nancy P.; Khouri, Hoda; Kitamoto, Katsuhiko; Kobayashi, Tetsuo; Konzack, Sven; Kulkarni, Resham D.; Kumagai, Toshitaka; Lafton, Anne; Latgé, Jean Paul; Li, Weixi; Lord, Angela; Lu, Charles; Majoros, William H.; May, Gregory S.; Miller, Bruce L.; Mohamoud, Yasmin Ali; Molina, Marı́a; Monod, Michel; Mouyna, Isabelle; Mulligan, Stephanie; Murphy, Lee; O'Neil, Susan; Paulsen, Ian T.; Peñalva, Miguel; Pertea, Mihaela; Price, Claire; Pritchard, Bethan; Quail, Michael A.; Rabbinowitsch, Ester; Rawlins, Neil; Rajandream, Marie Adèle; Reichard, Utz; Renauld, Hubert; Robson, Geoffrey D.; Córdoba, Santiago Rodrı́guez de; Rodrı́guez-Peña, José Manuel; Ronning, Catherine M.; Rutter, Simon; Salzberg, Steven L.; Sánchez, Miguel; Sánchez-Ferrero, Juan C.; Saunders, David; Seeger, Kathy; Squares, Rob; Squares, S.; Takeuchi, Michio; Tekaia, Fredj; Turner, Geoffrey; Aldana, Carlos R. Vázquez de; Weidman, Janice; White, Owen; Woodward, John R.; Yu, Jae Hyuk; Fraser, Claire M.; Galagan, James E.; Asai, Kiyoshi; Machida, Masayuki; Hall, Neil; Barrell, Bart; Denning, David W.

doi:10.1038/nature04332

Cited by 1,264 publications

(1,010 citation statements)

References 30 publications

Supporting

Mentioning

936

Contrasting

Unclassified

Order By: Relevance

“…A. fumigatus Af293 (a generous gift from P. Magee) was used as the wild-type parent strain in all experiments [45]. A list of all strains used in the experiments and their relevant genotypes is provided in Table 3.…”

Section: Methodsmentioning

confidence: 99%

Functional convergence of gliP and aspf1 in Aspergillus fumigatus pathogenicity

Liu

Solis

et al. 2018

Virulence

View full text Add to dashboard Cite

Gliotoxin contributes to the virulence of the fungus Aspergillus fumigatus in non-neutropenic mice that are immunosuppressed with corticosteroids. To investigate how the absence of gliotoxin affects both the fungus and the host, we used a nanoString nCounter to analyze their transcriptional responses during pulmonary infection of a non-neutropenic host with a gliotoxin-deficient ΔgliP mutant. We found that the ΔgliP mutation led to increased expression of aspf1, which specifies a secreted ribotoxin. Prior studies have shown that aspf1, like gliP, is not required for virulence in a neutropenic infection model, but its role in a non-neutropenic infection model has not been fully investigated. To investigate the functional significance of this up-regulation of aspf1, a Δaspf1 single mutant and a Δaspf1 ΔgliP double mutant were constructed. Both Δaspf1 and ΔgliP single mutants had reduced lethality in non-neutropenic mice, and a Δaspf1 ΔgliP double mutant had a greater reduction in lethality than either single mutant. Analysis of mice infected with these mutants indicated that the presence of gliP is associated with massive apoptosis of leukocytes at the foci of infection and inhibition of chemokine production. Also, the combination of gliP and aspf1 is associated with suppression of CXCL1 chemokine expression. Thus, aspf1 contributes to A. fumigatus pathogenicity in non-neutropenic mice and its up-regulation in the ΔgliP mutant may partially compensate for the absence of gliotoxin.Abbreviations:PAS: periodic acid-Schiff; PBS: phosphate buffered saline; ROS: reactive oxygen species; TUNEL: terminal deoxynucleotidyl transferase dUTP nick-end labeling

show abstract

Section: Methodsmentioning

confidence: 99%

Functional convergence of gliP and aspf1 in Aspergillus fumigatus pathogenicity

Liu

Solis

et al. 2018

Virulence

View full text Add to dashboard Cite

show abstract

“…12, 16, 20, 21 and 22) contain gaps surrounded by larger syntenic blocks, which appear to be recombination cold spots. These gaps resemble putative centromeres in the eight A. fumigatus chromosomes 12 . Due to their high repeat content, centromeres as well as ribosomal DNA (rDNA) repeats regions typically do not get assembled into supercontigs in fungal genomes 12,13 .…”

mentioning

confidence: 91%

“…These gaps resemble putative centromeres in the eight A. fumigatus chromosomes 12 . Due to their high repeat content, centromeres as well as ribosomal DNA (rDNA) repeats regions typically do not get assembled into supercontigs in fungal genomes 12,13 . Coincidentally, the upper gap on supercontig no.16 is not surrounded by large syntenic blocks and is likely to contain the rDNA region (Fig.…”

mentioning

confidence: 91%

Genome sequencing and analysis of the filamentous fungus Penicillium chrysogenum

et al. 2008

View full text Add to dashboard Cite

“…For screening flavin-dependent A. fumigatus proteins, the A. fumigatus Af293 proteome data set (AspGD; http://www.aspergillusgenome.org/download/domains/A_fumigatus_Af293/) from the Aspergillus database [19] was searched with the terms ”flavo”, ”flavin”, ”FMN” and ”FAD”. The resulting list was compared with A. fumigatus proteins identified in AspGD (http://www.aspgd.org) with terms ”flavo”, ”flavin”, ”FMN” and ”FAD” [20].…”

Section: Methodsmentioning

confidence: 99%

Riboflavin and pantothenic acid biosynthesis are crucial for iron homeostasis and virulence in the pathogenic mold Aspergillus fumigatus

et al. 2018

Self Cite

View full text Add to dashboard Cite

Background: Aspergillus fumigatus is the most prevalent airborne fungal pathogen, causing invasive fungal infections mainly in immunosuppressed individuals. Death rates from invasive aspergillosis remain high because of limited treatment options and increasing antifungal resistance. The aim of this study was to identify key fungal-specific genes participating in vitamin B biosynthesis in A. fumigatus. Because these genes are absent in humans they can serve as possible novel targets for antifungal drug development. Methods: By sequence homology we identified, deleted and analysed four key A. fumigatus genes (riboB, panA, pyroA, thiB) involved respectively in the biosynthesis of riboflavin (vitamin B2), pantothenic acid (vitamin B5), pyridoxine (vitamin B6) and thiamine (vitamin B1). Results: Deletion of riboB, panA, pyroA or thiB resulted in respective vitamin auxotrophy. Lack of riboflavin and pantothenic acid biosynthesis perturbed many cellular processes including iron homeostasis. Virulence in murine pulmonary and systemic models of infection was severely attenuated following deletion of riboB and panA, strongly reduced after pyroA deletion and weakly attenuated after thiB deletion. Conclusions: This study reveals the biosynthetic pathways of the vitamins riboflavin and pantothenic acid as attractive targets for novel antifungal therapy. Moreover, the virulence studies with auxotrophic mutants serve to identify the availability of nutrients to pathogens in host niches.Abbreviations: BPS: bathophenanthrolinedisulfonate; BSA: bovine serum albumin; CFU: colony forming unit; -Fe: iron starvation; +Fe: iron sufficiency; hFe: high iron; NRPSs: nonribosomal peptide synthetases; PKSs: polyketide synthaseses; wt: wild type

show abstract

Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus

Cited by 1,264 publications

References 30 publications

Functional convergence of gliP and aspf1 in Aspergillus fumigatus pathogenicity

Functional convergence of gliP and aspf1 in Aspergillus fumigatus pathogenicity

Genome sequencing and analysis of the filamentous fungus Penicillium chrysogenum

Riboflavin and pantothenic acid biosynthesis are crucial for iron homeostasis and virulence in the pathogenic mold Aspergillus fumigatus

Contact Info

Product

Resources

About