Open AccessFungal and host protein persulfidation are functionally correlated and modulate both virulence and antifungal response
Author(s) -
Mónica Sueiro-Olivares,
Jennifer Scott,
Sara Gago,
Dunja Petrovic,
Emilia Kouroussis,
Jasmina Živanović,
Yidong Yu,
Marlene Strobel,
Cristina Cunha,
Darren D. Thomson,
Rachael FortuneGrant,
Sina Thusek,
Paul Bowyer,
Andreas Beilhack,
Agostinho Carvalho,
Elaine Bignell,
Miloš R. Filipović,
Jorge Amich
Publication year - 2021
Publication title -
plos biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.127
H-Index - 271
eISSN - 1545-7885
pISSN - 1544-9173
DOI - 10.1371/journal.pbio.3001247
Subject(s) - biology , virulence , aspergillus fumigatus , pathogen , microbiology and biotechnology , aspergillosis , human pathogen , host–pathogen interaction , immune system , gene , host (biology) , immunology , genetics
Aspergillus fumigatus is a human fungal pathogen that can cause devastating pulmonary infections, termed “aspergilloses,” in individuals suffering immune imbalances or underlying lung conditions. As rapid adaptation to stress is crucial for the outcome of the host–pathogen interplay, here we investigated the role of the versatile posttranslational modification (PTM) persulfidation for both fungal virulence and antifungal host defense. We show that an A . fumigatus mutant with low persulfidation levels is more susceptible to host-mediated killing and displays reduced virulence in murine models of infection. Additionally, we found that a single nucleotide polymorphism (SNP) in the human gene encoding cystathionine γ-lyase (CTH) causes a reduction in cellular persulfidation and correlates with a predisposition of hematopoietic stem cell transplant recipients to invasive pulmonary aspergillosis (IPA), as correct levels of persulfidation are required for optimal antifungal activity of recipients’ lung resident host cells. Importantly, the levels of host persulfidation determine the levels of fungal persulfidation, ultimately reflecting a host–pathogen functional correlation and highlighting a potential new therapeutic target for the treatment of aspergillosis.