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 highosmolarity-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 M 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.

Disruption of the Phospholipase D Gene Attenuates the Virulence of Aspergillus fumigatus

“…In the present study, disruption of the pld gene in A. fumigatus had no influence on conidial morphology, hyphal growth rate, and biofilm formation, but it obviously attenuated virulence in hydrocortisone-treated mice. These findings are similar to those from the functional analysis of other genes of A. fumigatus, such as laeA (63), sho1 (43), mpkA (67), and hdaA (40). In mammalian cells, PLD interacts closely with the actin cytoskeleton to regulate cell shape changes.…”

“…Subsequently, a 2.9-kb PCR product of the hygromycin resistance gene (hph) was amplified from pDHt-hph-hindIII-sacI (62) using primers P3 and P4 (Table S2) to add the BglII and AsuII restriction sites. The hph fragment, which was digested with BglII and AsuII, was ligated into plasmid A to create plasmid B (43,62). Plasmid B was transformed into competent A. tumefaciens EHA105 using the freezethaw method (52,62).…”

Comparative genomics of MAP kinase and calcium–calcineurin signalling components in plant and human pathogenic fungi

“…Orthologues of Sho1 displaying conserved structural features were detected in all species studied, except S. pombe and R. oryzae. Sho1 orthologues were found to link oxidative stress to morphogenesis and cell wall biosynthesis in C. albicans (Bermejo et al, 2008;Roman et al, 2005) and to regulate hyphal growth, morphology and oxidant adaptation in A. fumigatus (Ma et al, 2008), but were dispensable for virulence in both human pathogens. The role of Sho1 in fungal pathogenicity on plants has not been determined yet.…”

Regulatory Circuitry Governing Fungal Development, Drug Resistance, and Disease

“…The deletion of the HOG pathway MAPK sakA results in abnormal germination and hyphal growth under different environmental conditions, including increased germination rates on reduced-nitrogen medium (638). Similarly, the Sho1 adaptor protein, which is an important component of upstream sensing in the HOG-MAPK pathway, is important for conidial germination (349). A ⌬sho1 mutant strain has reduced germination rates and produces irregular hyphae (349).…”

“…Similarly, the Sho1 adaptor protein, which is an important component of upstream sensing in the HOG-MAPK pathway, is important for conidial germination (349). A ⌬sho1 mutant strain has reduced germination rates and produces irregular hyphae (349).…”