10.6084/M9.FIGSHARE.6886586
Hong Liu
Hong
Liu
Wenjie Xu
Wenjie
Xu
Norma V. Solis
Norma V.
Solis
Carol Woolford
Carol
Woolford
Aaron P. Mitchell
Aaron P.
Mitchell
Scott G. Filler
Scott G.
Filler
Functional convergence of <i>gliP</i> and <i>aspf1</i> in <i>Aspergillus fumigatus</i> pathogenicity
<p>Gliotoxin contributes to the virulence of the fungus <i>Aspergillus fumigatus</i> in non-neutropenic mice that are immunosuppressed with corticosteroids. To investigate how the absence of gliotoxin affects both the fungus and the host, we used a nanoString nCounter to analyze their transcriptional responses during pulmonary infection of a non-neutropenic host with a gliotoxin-deficient Δ<i>gliP</i> mutant. We found that the Δ<i>gliP</i> mutation led to increased expression of <i>aspf1</i>, which specifies a secreted ribotoxin. Prior studies have shown that <i>aspf1</i>, like <i>gliP</i>, is not required for virulence in a neutropenic infection model, but its role in a non-neutropenic infection model has not been fully investigated. To investigate the functional significance of this up-regulation of <i>aspf1</i>, a Δ<i>aspf1</i> single mutant and a Δ<i>aspf1</i> Δ<i>gliP</i> double mutant were constructed. Both Δ<i>aspf1</i> and Δ<i>gliP</i> single mutants had reduced lethality in non-neutropenic mice, and a Δ<i>aspf1</i> Δ<i>gliP</i> double mutant had a greater reduction in lethality than either single mutant. Analysis of mice infected with these mutants indicated that the presence of <i>gliP</i> is associated with massive apoptosis of leukocytes at the foci of infection and inhibition of chemokine production. Also, the combination of <i>gliP</i> and <i>aspf1</i> is associated with suppression of CXCL1 chemokine expression. Thus, <i>aspf1</i> contributes to <i>A. fumigatus</i> pathogenicity in non-neutropenic mice and its up-regulation in the Δ<i>gliP</i> mutant may partially compensate for the absence of gliotoxin.</p> <p><b>Abbreviations</b>:PAS: periodic acid-Schiff; PBS: phosphate buffered saline; ROS: reactive oxygen species; TUNEL: terminal deoxynucleotidyl transferase dUTP nick-end labeling</p>
Medicine
Microbiology
Genetics
Immunology
Infectious Diseases
Plant Biology
Virology
Computational Biology
Taylor & Francis
2022
2022-12-30
2024-03-22
Dataset
206464 Bytes
10.1080/21505594.2018.1482182
CC BY 4.0