Sho1 and Msb2 Play Complementary but Distinct Roles in Stress Responses, Sexual Differentiation, and Pathogenicity of Cryptococcus neoformans.

Yee-Seul So,Yong-Sun Bahn,Jintao Xu,Michal A Olszewski,Goun Park,Juyeong Jang

doi:10.3389/fmicb.2018.02958

Yee-Seul So, Yong-Sun Bahn + Show 4 more

Open Access

https://doi.org/10.3389/fmicb.2018.02958

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Abstract

The high-osmolarity glycerol response (HOG) pathway is pivotal in environmental stress response, differentiation, and virulence of Cryptococcus neoformans, which causes fatal meningoencephalitis. A putative membrane sensor protein, Sho1, has been postulated to regulate HOG pathway, but its regulatory mechanism remains elusive. In this study, we characterized the function of Sho1 with relation to the HOG pathway in C. neoformans. Sho1 played minor roles in osmoresistance, thermotolerance, and maintenance of membrane integrity mainly in a HOG-independent manner. However, it was dispensable for cryostress resistance, primarily mediated through the HOG pathway. A mucinlike transmembrane (TM) protein, Msb2, which interacts with Sho1 in Saccharomyces cerevisiae, was identified in C. neoformans, but found not to interact with Sho1. MSB2 codeletion with SHO1 further decreased osmoresistance and membrane integrity, but not thermotolerance, of sho1Δ mutant, indicating that both factors play to some level redundant but also discrete roles in C. neoformans. Sho1 and Msb2 played redundant roles in promoting the filamentous growth in sexual differentiation in a Cpk1-independent manner, in contrast to the inhibitory effect of the HOG pathway in the process. Both factors also played redundant roles in maintaining cell wall integrity in the absence of Mpk1. Finally, Sho1 and Msb2 play distinct but complementary roles in the pulmonary virulence of C. neoformans. Overall, Sho1 and Msb2 play complementary but distinct roles in stress response, differentiation, and pathogenicity of C. neoformans.

Highlights

Sho1 Plays a Ssk1/Hog1-Independent Role in Osmosensing and Response in C. neoformans In S. cerevisiae, the well-established function of Sho1 is to mediate osmosensing signals generated by two mucin-like TM proteins, Msb2 and Hkr1 (Tatebayashi et al, 2007; Figures 1A,B)
The sho1 mutant was as resistant to 1.5-M NaCl or KCl as the WT strain, whereas ssk2, pbs2, and hog1 mutants were hypersensitive to the osmotic stresses (Figure 1C)
In the ssk1 mutant, Hog1 was unphosphorylated but started to be phosphorylated in response to osmotic shock, which was consistent with our previous finding (Bahn et al, 2006), and these Hog1 phosphorylation patterns were identical in the sho1 ssk1 mutant (Figure 1D)

Summary

Introduction

The high-osmolarity glycerol response (HOG) pathway is a multifunctional signal transduction pathway in pathogenic yeast, Cryptococcus neoformans, involved in sensing, responding, and adapting to a plethora of environmental cues, production of virulence factors (e.g., capsule and melanin), and ergosterol biosynthesis (Bahn et al, 2005; Bahn, 2008; Jung and Bahn, 2009; Ko et al, 2009; Bahn and Jung, 2013). Sho1 Plays a Ssk1/Hog1-Independent Role in Osmosensing and Response in C. neoformans In S. cerevisiae, the well-established function of Sho1 is to mediate osmosensing signals generated by two mucin-like TM proteins, Msb2 and Hkr1 (Tatebayashi et al, 2007; Figures 1A,B).

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