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Publication : Fungal and host protein persulfidation are functionally correlated and modulate both virulence and antifungal response.

First Author  Sueiro-Olivares M Year  2021
Journal  PLoS Biol Volume  19
Issue  6 Pages  e3001247
PubMed ID  34061822 Mgi Jnum  J:312328
Mgi Id  MGI:6715408 Doi  10.1371/journal.pbio.3001247
Citation  Sueiro-Olivares M, et al. (2021) Fungal and host protein persulfidation are functionally correlated and modulate both virulence and antifungal response. PLoS Biol 19(6):e3001247
abstractText  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 gamma-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.
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