Aspergillus terreus

Convenor(s):

Cornelia Lass-Flörl (cornelia.lass-floerl@i-med.ac.at)

Overview

The A. terreus working group consists of a diverse group of mycologists, clinicians and molecular biologists. This unique consortium will work towards the common goal of augmenting existing knowledge on the biology, genetic diversity, population dynamics, clinical epidemiology, virulence and antifungal susceptibilities of the emerging fungal pathogen A. terreus. The working group will sustain a communication network through which the members can exchange research idea and thoughts freely and will also function as a portal for the group to meet and exchange research data.

 

Objectives:

1. Explore the genetic diversity and population dynamics of A. terreus. Under this aim, we propose to:

a. develop a comprehensive culture repository comprising both clinical and environmental isolates of A. terreus and other isolates in section Terrei,

b. design a multilocus sequence typing scheme (MLST) for species identification in Section Terrei,

c. using the repository and the MLST scheme, generate data on the genetic diversity and population dynamics of A. terreus,

d. establish a new typing method based on the polymorphism of tandem repeats in A. terreus,

e. recognize and validly publish new species.

2. Understand the epidemiology of A. terreus by

a. Developing a microsatellite marker panel for strain discrimination and use test this panel on several environmental and clinical isolates of A. terreus to understand the molecular epidemiology of this organism
b. Elucidating the clinical epidemiology of A. terreus

3. Investigate amphotericin B resistance in A. terreus

4. Study immune response and virulence potential of A. terreus

5. Set up animal models to establish in vivo and in vitro correlation

6. Study clinical infections.

7. Create an A. terreus proteome map

8. Build a web-based database for all participants for studies.

9. Prepare a genomic bank for A. terreus which will be use for the identification and characterization of some putative virulence factors of the fungus (e.g. anti-oxidant systems, proteases, etc.).

10. Exo-metabolomics on Aspergillus terreus and related species.

Achievements

1. Under construction: “TerrNet -A Global Aspergillus terreus Surveillance Study (An initiative of the ISHAM Aspergillus terreus working group and ECMM)” - still running:
a.  Clinical data collection: done
b. Strain collection: still ongoing
c. Susceptibility testing: ongoing
d. Typing: ongoing

2. Genetic diversity and population dynamics: done

3. Investigating A. terreus resistance: done

Publications

Lass-Florl C et al. Molecular typing of A. terreus isolates collected in Houston, Texas and Innsbruck, Austria: evidence of great genetic diversity. J Clin Microbiol. 2007, Aug;45(8):2686-90. Epub 2007 Jun 20.

Lass-Flörl C et al. In Vitro Activities of Various Antifungal Drugs against Aspergillus terreus: Global Assessment using EUCAST Methodology. Antimicrob Agents Chemother. 2008, 53(2): 794-795.

Blum G et al. A 1-year Aspergillus terreus surveillance study at the University Hospital of Innsbruck: molecular typing of environmental and clinical isolates. Clin Microbiol Infect. 2008, 14(12):1146-51.

Blum G et al. Potential basis for amphotericin B resistance in Aspergillus terreus. Antimicrob Agents Chemother. 2008, 52(4):1553-5.

Elad D et al. Transuterine transmission of Aspergillus terreus in a case of disseminated canine aspergillosis. Medical Mycology 2008;46:175-178. 2.005; 6/128.

Deak E et al. Aspergillus terreus accessory conidia are unique in surface architecture, cell wall composition and germination kinetics. PLoS One. 2009, 4(10):e7673.

Balajee SA et al.  ISHAM Working Group on A. terreus. Aspergillus alabamensis, a new clinically relevant species in the section Terrei. Eukaryot Cell. 2009, 8(5):713-22. Epub 2009 Mar 20.

Balajee SA. Aspergillus terreus complex. Med Mycol. 2009, 47 Suppl 1:S42-6. Epub 2009 Mar 17.

Ben-Ami R et al. Interstrain variability in the virulence of Aspergillus fumigatus and Aspergillus terreus in a Toll-deficient Drosophila fly model of invasive aspergillosis. Med Mycol. 2010, 38: 310-317.

Deak E et al. Aspergillus terreus accessory conidia induce inflammatory responses during infection in a pulmonary model of aspergillosis possibly due to early and sustained ß-glucan display. Virulence 2011, 2(3): 200-207.

Samson RA et al. . New species in Aspergillus section Terrei. Stud Mycol 2011, 69: 39-55.

Blum G et al. In vitro and in vivo role of heat shock protein 90 in Amphotericin B resistance of Aspergillus terreus. Clin Microbiol Infect 2012, doi: 10.1111/j.1469-0691.2012.03848.x.

Gressler M et al. Multifactorial induction of an orphan PKS-NRPS gene cluster in Aspergillus terreus. Chem Biol. 2011, 18: 198-209.

Slesiona S et al. Persistence versus escape: Aspergillus terreus and Aspergillus fumigatus employ different strategies during interactions with macrophages. PloS One 2012, 7: e31223.

Slesiona S et al. Murine infection models for Aspergillus terreus pulmonary aspergillosis reveal long-term persistence of conidia and liver degeneration. J Infect Dis 2012, 205: 1268-1277.

Lass-Flörl C. Aspergillus terreus: how inoculums size and host characteristics affect its virulence. J Infect Dis 2012, 205: 1192-1194.

Samson RA et al. New species in Aspergillus section Terrei. Studies in Mycology 2011, 69: 39-55.

Semis R et al. Antifungal combinations with Intralipid formulation of polyenes against Aspergillus terreus. Mycoses 2012, 55: 114-115.

Lewis RE et al. High-dose induction liposomal amphotericin B followed by de-escalation is effective inexperimental Aspergillus terreus pneumonia. J Antimicrob Chemother 2013;68: 1148-1151.

Blum G et al. New insights into Amphotericin B resistance in Aspergillus terreus. Antimicrob Agents Chemother 2013;57: 1583-1588.

Blum G et al. In vitro and in vivo role of heat shock protein 90 in Amphotericin B resistance of Aspergillus terreus. Clin Microbiol Infect 2013;19: 50-55.

Speth C et al. Virulence and thrombocyte affectation of two Aspergillus terreus isolates differing in Amphotericin B susceptibility. Med Microbiol Immunol 2013;202: 379-389.

Blatzer M et al. Amphotericin B resistance in Aspergillus terreus is overpowered by co-application of pro-oxidants. Antioxid Redox Signal 2015;23:1424-1438.

Blatzer M et al. Blocking Hsp70 enhances the efficiency of amphotericin B treatment against resistant Aspergillus terreus strains. Antimicrob Agents Chemother. 2015;59:3778-3788.

Lackner M et al. (2015) Geographically predominant geotypes of Aspergillus terreus species complex in Austria: a microsatellite typing study. Clin Microbiol Infect 2015 [Epub ahead of print]

Maurer E et al. Galleria mellonella as a host model to study Aspergillus terreus virulence and amphotericin B resistance. Virulence 2015;6:591-598.

Fernández MS et al. In vitro activities of amphotericin B, terbinafine, and azole drugs against clinical and environmental isolates of Aspergillus terreus sensu stricto. Antimicrob Agents Chemother 2015;59:3619-3622.

 

Conference Presentations:

Molecular phylogeny of Aspergillus terreus. Balajee SA. Oral presentation at the meeting an "Aspergillus systematics in the genomic era". 2007.

The A. terreus complex. Balajee SA. Oral presentation. Joint meeting of the Netherlands Society for Medical Mycology. 2007.

Epidemiology of Aspergillus terreus Infection in Transplant Recipients from Transplant Associated Infection Surveillance Network (TRANSNET). J. W. Baddley, K. A. Marr, D. R. Andes, D. P. Kontoyiannis, T.F Patterson, E.J. Anaissie, T.J. Walsh, B. D. Alexander, M. Schuster, R. A. Oster, and P. G. Pappas. IDSA. 2007.

A one year Aspergillus terreus surveillance study at the University Hospital Innsbruck: molecular typing of environmental and clinical isolates. Lass Florl et al.

Evaluation of liposomal dose-escalation and de-escalation strategies in a neutropenic murine model of Aspergillus terreus pneumonia. Russell E. Lewis, Nathan D. Albert, Guangling Liao, and Dimitrios P. Kontoyiannis. Abstract, Advance Against Aspergillosis, Rome Italy, 2010.

Preliminary data from TerrNet – A global Aspergillus terreus surveillance study. Lass-Flörl C. Oral presentation at the 19th ISHAM Conference, Melbourne/Australia, 2015.

Polyene resistance in A. terreus. Jukic E. Oral presentation at the 19th ISHAM Conference, Melbourne/Australia, 2015.