Authors

"Monica Sueiro-Olivares1
, Jennifer Scott1
, Sara GagoID1
, Dunja Petrovic2,3,
Emilia Kouroussis2,3, Jasmina Zivanovic2,3, Yidong Yu4
, Marlene Strobel4
,
Cristina CunhaID5,6, Darren ThomsonID1
, Rachael Fortune-Grant1
, Sina Thusek4
,
Paul Bowyer1
, Andreas Beilhack4
, Agostinho CarvalhoID5,6, Elaine Bignell1¤a
, Milos
R. Filipovic7
, Jorge AmichID1
*"

Affiliations

"1 Manchester Fungal Infection Group (MFIG), School of Biological Sciences, Faculty of Biology, Medicine
and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, United
Kingdom, 2 Centre National de la Recherche Scientifique (CNRS), Institut de Biochimie et Genetique
Cellulaires (IBGC), Bordeaux, France, 3 Universite´ de Bordeaux, Institut de Biochimie et Genetique
Cellulaires (IBGC), Bordeaux, France, 4 Interdisciplinary Center for Clinical Research (IZKF) Laboratory for
Experimental Stem Cell Transplantation, Department of Internal Medicine II, University Hospital, Wu¨rzburg,
Germany, 5 Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho,
Braga, Portugal, 6 Life and Health Sciences Research Institute (ICVS)/Biomaterials, Biodegradables and
Biomimetics (3B’s)—PT Government Associate Laboratory, Guimarães, Braga, Portugal, 7 Leibniz Institute
for Analytical Sciences (ISAS), Dortmund, Germany"

Topic

Microbiology

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.

DOI: https://dx.doi.org/10.1371%2Fjournal.pbio.3001247

Extract

Fluorescence was captured using a CoolLED pE-2 excitation system

Product Associated Features

The pE-2 was one of the first highly controllable LED Illumination Systems available to offer wavelength flexibility, including 635 nm and 475 nm for Cy5 and Alexa488 excitation in this application.

Product Type

-

Journal

PLoS. Biol.

Year of Publication

2021

Country of Publication

France, Germany, Portugal, UK, USA