Cell reports (Cambridge), 2017-05, Vol.19 (5), p.1008-1021
2017
Details
- Autor(en) / Beteiligte
- Titel
- Aspergillus fumigatus Copper Export Machinery and Reactive Oxygen Intermediate Defense Counter Host Copper-Mediated Oxidative Antimicrobial Offense
- Ist Teil von
- Cell reports (Cambridge), 2017-05, Vol.19 (5), p.1008-1021
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2017
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The Fenton-chemistry-generating properties of copper ions are considered a potent phagolysosome defense against pathogenic microbes, yet our understanding of underlying host/microbe dynamics remains unclear. We address this issue in invasive aspergillosis and demonstrate that host and fungal responses inextricably connect copper and reactive oxygen intermediate (ROI) mechanisms. Loss of the copper-binding transcription factor AceA yields an Aspergillus fumigatus strain displaying increased sensitivity to copper and ROI in vitro, increased intracellular copper concentrations, decreased survival in challenge with murine alveolar macrophages (AMΦs), and reduced virulence in a non-neutropenic murine model. ΔaceA survival is remediated by dampening of host ROI (chemically or genetically) or enhancement of copper-exporting activity (CrpA) in A. fumigatus. Our study exposes a complex host/microbe multifactorial interplay that highlights the importance of host immune status and reveals key targetable A. fumigatus counter-defenses. [Display omitted] •Aspergillus fumigatus infection activates the host copper (Cu) transporter Ctr1•AceA is the A. fumigatus transcription factor coordinating Cu-dependent defense•A. fumigatus detoxifies high copper levels through the P-type ATPase CrpA•Activation of copper export restores virulence of aceA-deficient strains Wiemann et al. find that Aspergillus fumigatus employs the copper-sensing transcription factor AceA to express the copper exporter CrpA as a defense mechanism against macrophages. Copper and reactive oxygen intermediate attack and defense are inextricably connected on the side of both host and pathogen during infection.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2211-1247eISSN: 2211-1247DOI: 10.1016/j.celrep.2017.04.019Titel-ID: cdi_doaj_primary_oai_doaj_org_article_153c382f8c2f412281161132bf7a71b6
- Format
- –
- Schlagworte
- Animals, Aspergillus - genetics, Aspergillus - metabolism, Aspergillus - pathogenicity, Aspergillus fumigatus, AtfA, ATP7A, Carrier Proteins - genetics, Carrier Proteins - metabolism, Cells, Cultured, CGD, copper, Copper - metabolism, CrpA, CTR1, Fungal Proteins - genetics, Fungal Proteins - metabolism, Host-Pathogen Interactions, Macrophages - microbiology, Mice, Mice, Inbred C57BL, Mice, Inbred ICR, P-type ATPases - genetics, P-type ATPases - metabolism, PHOX, Reactive Oxygen Species - metabolism, ROI, ROS, Transcription Factors - genetics, Transcription Factors - metabolism, Virulence - genetics