Evolutionary origin and population diversity of a cryptic hybrid pathogen

Jacob L Steenwyk; Sonja Knowles; Rafael W Bastos; Charu Balamurugan; David Rinker; Matthew E Mead; Christopher D Roberts; Huzefa A Raja; Yuanning Li; Ana Cristina Colabardini; Patrícia Alves de Castro; Thaila Fernanda Dos Reis; Adiyantara Gumilang; María Almagro-Molto; Alexandre Alanio; Dea Garcia-Hermoso; Endrews Delbaje; Laís Pontes; Camila Figueiredo Pinzan; Angélica Zaninelli Schreiber; David Canóvas; Rafael Sanchez Luperini; Katrien Lagrou; Egídio Torrado; Fernando Rodrigues; Nicholas H Oberlies; Xiaofan Zhou; Gustavo H Goldman; Antonis Rokas

doi:10.1038/s41467-024-52639-1

Evolutionary origin and population diversity of a cryptic hybrid pathogen

Nat Commun. 2024 Sep 28;15(1):8412. doi: 10.1038/s41467-024-52639-1.

Authors

Jacob L Steenwyk^{1

2

3}, Sonja Knowles⁴, Rafael W Bastos^{5

6}, Charu Balamurugan^{2

3}, David Rinker^{2

3}, Matthew E Mead^{2

3

7}, Christopher D Roberts⁴, Huzefa A Raja⁴, Yuanning Li⁸, Ana Cristina Colabardini⁵, Patrícia Alves de Castro⁵, Thaila Fernanda Dos Reis⁵, Adiyantara Gumilang^{2

3}, María Almagro-Molto⁹, Alexandre Alanio^{10

11}, Dea Garcia-Hermoso¹⁰, Endrews Delbaje⁵, Laís Pontes⁵, Camila Figueiredo Pinzan⁵, Angélica Zaninelli Schreiber¹², David Canóvas^{13

14}, Rafael Sanchez Luperini⁵, Katrien Lagrou^{15

16}, Egídio Torrado¹⁷, Fernando Rodrigues¹⁷, Nicholas H Oberlies⁴, Xiaofan Zhou¹⁸, Gustavo H Goldman^{19

20}, Antonis Rokas^{21

22}

Affiliations

¹ Howards Hughes Medical Institute and the Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, USA.
² Vanderbilt University, Department of Biological Sciences, VU Station B #35-1634, Nashville, USA.
³ Evolutionary Studies Initiative, Vanderbilt University, Nashville, USA.
⁴ Department of Chemistry & Biochemistry, University of North Carolina at Greensboro, Greensboro, USA.
⁵ Faculdade de Ciencias Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil.
⁶ Department of Microbiology and Parasitology, Bioscience Center, Federal University of Rio Grande do Norte, Natal-RN, Brazil.
⁷ Ginkgo Bioworks, 27 Drydock Avenue, 8th Floor, Boston, USA.
⁸ Institute of Marine Science and Technology, Shandong University, 72 Binhai Road, Qingdao, China.
⁹ Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Faculty of Medicine, Ludwig Maximilian University, Munich, Germany.
¹⁰ Institut Pasteur, Paris Cité University, National Reference Center for Invasives Mycoses and Antifungals, Translational Mycology Research Group, Mycology Department, Paris, France.
¹¹ Laboratoire de parasitologie-mycologie, AP-HP, Hôpital Saint-Louis, Paris, France.
¹² School of Medical Sciences, State University of Campinas, Campinas, Brazil.
¹³ Departamento de Genética, Facultad de Biología, Universidad de Sevilla, Seville, Spain.
¹⁴ Clinical Microbiology Unit. Synlab Laboratory at Viamed Sta. Ángela de la Cruz Hospital, Seville, Spain.
¹⁵ Department of Microbiology, Immunology and Transplantation, Katholieke Universiteit Leuven, Leuven, Belgium.
¹⁶ Department of Laboratory Medicine and National Reference Centre for Mycosis, University Hospitals Leuven, Leuven, Belgium.
¹⁷ Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4715-495 Braga, Portugal; ICVS/3B's-PT Government Associate Laboratory, Braga, Portugal.
¹⁸ Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Province Key Laboratory of Microbial Signals and Disease Control, Integrative Microbiology Research Centre, South China Agricultural University, Guangzhou, China.
¹⁹ Faculdade de Ciencias Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil. [email protected].
²⁰ National Institute of Science and Technology in Human Pathogenic, Fungi, Brazil. [email protected].
²¹ Vanderbilt University, Department of Biological Sciences, VU Station B #35-1634, Nashville, USA. [email protected].
²² Evolutionary Studies Initiative, Vanderbilt University, Nashville, USA. [email protected].

Abstract

Cryptic fungal pathogens pose disease management challenges due to their morphological resemblance to known pathogens. Here, we investigated the genomes and phenotypes of 53 globally distributed isolates of Aspergillus section Nidulantes fungi and found 30 clinical isolates-including four isolated from COVID-19 patients-were A. latus, a cryptic pathogen that originated via allodiploid hybridization. Notably, all A. latus isolates were misidentified. A. latus hybrids likely originated via a single hybridization event during the Miocene and harbor substantial genetic diversity. Transcriptome profiling of a clinical isolate revealed that both parental subgenomes are actively expressed and respond to environmental stimuli. Characterizing infection-relevant traits-such as drug resistance and growth under oxidative stress-revealed distinct phenotypic profiles among A. latus hybrids compared to parental and closely related species. Moreover, we identified four features that could aid A. latus taxonomic identification. Together, these findings deepen our understanding of the origin of cryptic pathogens.

MeSH terms

Aspergillus* / genetics
Aspergillus* / isolation & purification
COVID-19* / epidemiology
COVID-19* / virology
Evolution, Molecular
Gene Expression Profiling / methods
Genetic Variation*
Genome, Fungal* / genetics
Humans
Hybridization, Genetic
Phenotype
Phylogeny*
SARS-CoV-2 / genetics
SARS-CoV-2 / isolation & purification

Abstract

MeSH terms

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