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As rapid adaptation to stress is crucial for the outcome of the host\u2013pathogen 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<jats:italic>A<\/jats:italic>.<jats:italic>fumigatus<\/jats:italic>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 \u03b3-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\u2019 lung resident host cells. Importantly, the levels of host persulfidation determine the levels of fungal persulfidation, ultimately reflecting a host\u2013pathogen functional correlation and highlighting a potential new therapeutic target for the treatment of aspergillosis.<\/jats:p>","DOI":"10.1371\/journal.pbio.3001247","type":"journal-article","created":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T17:46:40Z","timestamp":1622569600000},"page":"e3001247","update-policy":"https:\/\/doi.org\/10.1371\/journal.pbio.corrections_policy","source":"Crossref","is-referenced-by-count":19,"title":["Fungal and host protein persulfidation are functionally correlated and modulate both virulence and antifungal 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