The Sho1 sensor regulates growth, morphology, and oxidant adaptation in Aspergillus fumigatus but is not essential for development of invasive pulmonary aspergillosis

Department of Dermatology, Peking University First Hospital, and Research Center for Medical Mycology, Peking University, Beijing, China; Department of Microbiology & Immunology, Georgetown University Medical Center, Washington, DC 20057, USA

^* To whom correspondence should be addressed. Email: lrymm{at}medmail.com.cn.

	Abstract

Aspergillus fumigatus is an important opportunistic fungal pathogen. It 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 (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 an important element of one of the two upstream branches of the HOG-MAPK pathway in Saccharomyces cerevisiae, a signal transduction cascade involved in adaptation to stress. We have constructed a sho1 mutant of A. fumigatus, MA21. Both 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. The gene deletion mutant is sensitive to 2.5 mM hydrogen peroxide and 15 µM menadione, but it appears to be minimally sensitive to diamide compared to the wild type strain. In an immunosuppressed mouse model, the mutant is as virulent as the wild type or the 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 S. cerevisiae.