title: The sho1 sensor regulates growth, morphology, and oxidant adaptation in Aspergillus fumigatus but is not essential for development of invasive pulmonary aspergillosis.
abstract: Aspergillus fumigatus is an important opportunistic fungal pathogen. This organism must be able to adapt to stress changes in the microenvironment during host invasion and systemic spread. The high-osmolarity-glycerol (HOG) mitogen-activated protein kinase (HOG-MAPK) signaling pathway plays an important role in regulating morphology, growth, and adaptation to stress and virulence in a number of fungal pathogens. The Sho1 adaptor protein is one important element of the two upstream branches of the HOG-MAPK pathway in Saccharomyces cerevisiae, a signal transduction cascade involved in adaptation to stress. We constructed a sho1 mutant of A. fumigatus, MA21. Both the growth and germination rates of the mutant were reduced, and the MA21 strain had an irregular hyphal morphology characterized by reduced production of phialides and conidia. This gene deletion mutant was sensitive to 2.5 mM hydrogen peroxide and 15 muM menadione, but it appeared to be minimally sensitive to diamide compared to the wild-type strain. In an immunosuppressed mouse model, the mutant was as virulent as the wild-type or complemented strains. These data support the idea that the loss of sho1, a highly conserved gene among fungi, regulates radial hyphal growth and delays germination of A. fumigatus conidia. In addition, the sho1 gene has a visible effect in the adaptation to oxidative stress in A. fumigatus similar to that in S. cerevisiae.
authors.affiliation: Department of Dermatology, Peking University First Hospital, and Research Center for Medical Mycology, Peking University, No. 8 Xishiku St., West District, Beijing 100034, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.forename: Jianjun
authors.initials: J
authors.lastname: Qiao
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wan
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wang
authors.forename: Richard
authors.initials: R
authors.lastname: Calderone
authors.forename: Ruoyu
authors.initials: R
authors.lastname: Li
mesh_terms: D000818:Animals; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000382:microbiology*; D001232:Aspergillus fumigatus / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress; D013172:Spores, Fungal
chemical_list: D005656:Fungal Proteins