Fungal and host protein persulfidation are functionally correlated and modulate both virulence and antifungal response
Gago, Sara; orcid: 0000-0002-7027-4598
Cunha, Cristina; orcid: 0000-0002-6002-5782
Thomson, Darren; orcid: 0000-0002-4800-7717
Carvalho, Agostinho; orcid: 0000-0001-8935-8030
Filipovic, Milos R.
Amich, Jorge; orcid: 0000-0002-8987-5115; email: email@example.com
MetadataShow full item record
AbstractAspergillus 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.
CitationPLOS Biology, volume 19, issue 6, page e3001247
PublisherPublic Library of Science
DescriptionFrom PLOS via Jisc Publications Router
History: received 2020-06-02, accepted 2021-04-27, collection 2021-06, epub 2021-06-01
Publication status: Published
Funder: Medical Research Council; funder-id: http://dx.doi.org/10.13039/501100000265; Grant(s): MR/N008707/1
Funder: National Centre for the Replacement, Refinement and Reduction of Animals in Research; funder-id: http://dx.doi.org/10.13039/501100000849; Grant(s): NC/P002390/1
Funder: Fundação para a Ciência e a Tecnologia; funder-id: http://dx.doi.org/10.13039/501100001871; Grant(s): SFRH/BPD/96176/201
Funder: Fundação para a Ciência e a Tecnologia; funder-id: http://dx.doi.org/10.13039/501100001871; Grant(s): IF/00735/2014
Funder: deutsche forschungsgemeinschaft; Grant(s): CRC/TRR 124
Funder: Fondation de l'Avenir pour la Recherche Médicale Appliquée; funder-id: http://dx.doi.org/10.13039/100007380
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