In:
PLOS Biology, Public Library of Science (PLoS), Vol. 19, No. 6 ( 2021-6-1), p. e3001247-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1545-7885
DOI:
10.1371/journal.pbio.3001247
DOI:
10.1371/journal.pbio.3001247.g001
DOI:
10.1371/journal.pbio.3001247.g002
DOI:
10.1371/journal.pbio.3001247.g003
DOI:
10.1371/journal.pbio.3001247.g004
DOI:
10.1371/journal.pbio.3001247.t001
DOI:
10.1371/journal.pbio.3001247.t002
DOI:
10.1371/journal.pbio.3001247.s001
DOI:
10.1371/journal.pbio.3001247.s002
DOI:
10.1371/journal.pbio.3001247.s003
DOI:
10.1371/journal.pbio.3001247.s004
DOI:
10.1371/journal.pbio.3001247.s005
DOI:
10.1371/journal.pbio.3001247.s006
DOI:
10.1371/journal.pbio.3001247.s007
DOI:
10.1371/journal.pbio.3001247.s008
DOI:
10.1371/journal.pbio.3001247.s009
DOI:
10.1371/journal.pbio.3001247.s010
DOI:
10.1371/journal.pbio.3001247.s011
DOI:
10.1371/journal.pbio.3001247.s012
DOI:
10.1371/journal.pbio.3001247.s013
DOI:
10.1371/journal.pbio.3001247.s014
DOI:
10.1371/journal.pbio.3001247.s015
DOI:
10.1371/journal.pbio.3001247.s016
DOI:
10.1371/journal.pbio.3001247.s017
DOI:
10.1371/journal.pbio.3001247.s018
DOI:
10.1371/journal.pbio.3001247.r001
DOI:
10.1371/journal.pbio.3001247.r002
DOI:
10.1371/journal.pbio.3001247.r003
DOI:
10.1371/journal.pbio.3001247.r004
DOI:
10.1371/journal.pbio.3001247.r005
DOI:
10.1371/journal.pbio.3001247.r006
DOI:
10.1371/journal.pbio.3001247.r007
DOI:
10.1371/journal.pbio.3001247.r008
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2126773-X
Permalink