Investigation of enhanced virulence mechanisms in Aspergillus fumigatus isolates from the International Space Station.

A. Blachowicz1,2, J. Romsdahl1 , N. Raffa3 , N. P. Keller3 , K. Venkateswaran2 , C. C. C. Wang1,4

Author address: 

1) Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA; 2) Biotechnology and Planetary Protection Group, Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA; 3) Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI ; 4) Department of Chemistry, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA.

Abstract: 

Aspergillus fumigatus, one of many fungal isolates identified in a recent Microbial Observatory Study on the International Space Station (ISS-MO study), is a ubiquitous saprophytic fungus. Its vast adaptation capacity enables it to be omnipresent in the environment and to be a successful opportunistic pathogen. A. fumigatus causes variety of health conditions ranging from allergies to potentially life-threatening invasive aspergillosis (IA) in immunocompromised individuals. Initial characterization of two A. fumigatus ISS-isolates, ISSFT-021 and IF1SW-F4, showed no outstanding differences in their genomes and secondary metabolite (SM) profiles when compared to clinical isolates CEA10 and Af293, however both isolates were significantly more lethal in a larval zebra fish model of IA. Considering that A. fumigatus becomes more virulent in space posing a potential threat to the astronauts’ health, we investigated molecular changes in the proteome of ISS-isolated strains. Furthermore, we attempted to elucidate the mechanisms of observed enhanced virulence in “space” strains. We created Af293 mutants deficient in the five spore associated SMs (DHN-melanin, endocrocin, trypacidin, fumigaclavine and fumiquinazoline) that are also known to contribute to virulence or toxicity. We tested these mutants for UV-C sensitivity and virulence in in two larval zebra fish models characterized by neutrophil and macrophage deficiency. Further, an evolution study using clinical isolate Af293 was conducted to examine its adaptation to sub-lethal doses of UVC. The first and last generations of the controlled evolution study will be tested for virulence and analyzed for any molecular changes. Such in depth analyses are imperative for understanding the mechanisms of enhanced virulence in A. fumigatus and may result in the development of preventive measures against IA. Understanding the possible molecular alterations triggered by irradiation remains crucial in the light of future long-term manned space flights to both ensure the astronaut’s health and maintain the closed habitat.

2019

abstract No: 

251W

Full conference title: 

30th Fungal Genetics Conference 2019
    • Fungal Genetics Conference 30th (2019)