Universität zu Köln

Steenwyk, Jacob L. ORCID: 0000-0002-8436-595X, Mead, Matthew E., de Castro, Patricia Alves, Valero, Clara, Damasio, Andre, dos Santos, Renato A. C., Labella, Abigail L., Li, Yuanning, Knowles, Sonja L., Raja, Huzefa A., Oberlies, Nicholas H., Zhou, Xiaofan, Cornely, Oliver A., Fuchs, Frieder ORCID: 0000-0001-7075-5378, Koehler, Philipp ORCID: 0000-0002-7386-7495, Goldman, Gustavo H. and Rokas, Antonis (2021). Genomic and Phenotypic Analysis of COVID-19-Associated Pulmonary Aspergillosis Isolates of Aspergillus fumigatus. Microbiol. Spectr., 9 (1). WASHINGTON: AMER SOC MICROBIOLOGY. ISSN 2165-0497

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Abstract

The ongoing global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for coronavirus disease 2019 (COVID-19), first described in Wuhan, China. A subset of COVID-19 patients has been reported to have acquired secondary infections by microbial pathogens, such as opportunistic fungal pathogens from the genus Aspergillus. To gain insight into COVID-19-associated pulmonary aspergillosis (CAPA), we analyzed the genomes and characterized the phenotypic profiles of four CAPA isolates of Aspergillus fumigatus obtained from patients treated in the area of North Rhine-Westphalia, Germany. By examining the mutational spectrum of single nucleotide polymorphisms, insertiondeletion polymorphisms, and copy number variants among 206 genes known to modulate A. fumigatus virulence, we found that CAPA isolate genomes do not exhibit significant differences from the genome of the Af293 reference strain. By examining a number of factors, including virulence in an invertebrate moth model, growth in the presence of osmotic, cell wall, and oxidative stressors, secondary metabolite biosynthesis, and the MIC of antifungal drugs, we found that CAPA isolates were generally, but not always, similar to A. fumigatus reference strains Af293 and CEA17. Notably, CAPA isolate D had more putative loss-of-function mutations in genes known to increase virulence when deleted. Moreover, CAPA isolate D was significantly more virulent than the other three CAPA isolates and the A. fumigatus reference strains Af293 and CEA17, but similarly virulent to two other clinical strains of A. fumigatus. These findings expand our understanding of the genomic and phenotypic characteristics of isolates that cause CAPA. IMPORTANCE The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID19), has already killed millions of people. COVID-19 patient outcome can be further complicated by secondary infections, such as COVID-19-associated pulmonary aspergillosis (CAPA). CAPA is caused by Aspergillus fungal pathogens, but there is little information about the genomic and phenotypic characteristics of CAPA isolates. We conducted genome sequencing and extensive phenotyping of four CAPA isolates of Aspergillus fumigatus from Germany. We found that CAPA isolates were often, but not always, similar to other reference strains of A. fumigatus across 206 genetic determinants of infection-relevant phenotypes, including virulence. For example, CAPA isolate D was more virulent than other CAPA isolates and reference strains in an invertebrate model of fungal disease, but similarly virulent to two other clinical strains. These results expand our understanding of COVID-19-associated pulmonary aspergillosis.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Steenwyk, Jacob L. UNSPECIFIED orcid.org/0000-0002-8436-595X UNSPECIFIED Mead, Matthew E. UNSPECIFIED UNSPECIFIED UNSPECIFIED de Castro, Patricia Alves UNSPECIFIED UNSPECIFIED UNSPECIFIED Valero, Clara UNSPECIFIED UNSPECIFIED UNSPECIFIED Damasio, Andre UNSPECIFIED UNSPECIFIED UNSPECIFIED dos Santos, Renato A. C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Labella, Abigail L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Li, Yuanning UNSPECIFIED UNSPECIFIED UNSPECIFIED Knowles, Sonja L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Raja, Huzefa A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Oberlies, Nicholas H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhou, Xiaofan UNSPECIFIED UNSPECIFIED UNSPECIFIED Cornely, Oliver A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fuchs, Frieder UNSPECIFIED orcid.org/0000-0001-7075-5378 UNSPECIFIED Koehler, Philipp UNSPECIFIED orcid.org/0000-0002-7386-7495 UNSPECIFIED Goldman, Gustavo H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rokas, Antonis UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-597490
DOI:	10.1128/Spectrum.00010-21
Journal or Publication Title:	Microbiol. Spectr.
Volume:	9
Number:	1
Date:	2021
Publisher:	AMER SOC MICROBIOLOGY
Place of Publication:	WASHINGTON
ISSN:	2165-0497
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ANTIFUNGAL DRUG-RESISTANCE; COPY NUMBER; VIRULENCE; SEQUENCE; FUNGAL; GENES; FERMENTATION; CONIDIATION; INHIBITION; DISCOVERY Multiple languages Microbiology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59749