The novel Dbl homology/BAR domain protein, MsgA, of Talaromyces marneffei regulates yeast morphogenesis during growth inside host cells

Harshini Weerasinghe,Alex Andrianopoulos,Hayley E Bugeja

doi:10.1038/s41598-020-79593-4

Abstract

Microbial pathogens have evolved many strategies to evade recognition by the host immune system, including the use of phagocytic cells as a niche within which to proliferate. Dimorphic pathogenic fungi employ an induced morphogenetic transition, switching from multicellular hyphae to unicellular yeast that are more compatible with intracellular growth. A switch to mammalian host body temperature (37 °C) is a key trigger for the dimorphic switch. This study describes a novel gene, msgA, from the dimorphic fungal pathogen Talaromyces marneffei that controls cell morphology in response to host cues rather than temperature. The msgA gene is upregulated during murine macrophage infection, and deletion results in aberrant yeast morphology solely during growth inside macrophages. MsgA contains a Dbl homology domain, and a Bin, Amphiphysin, Rvs (BAR) domain instead of a Plekstrin homology domain typically associated with guanine nucleotide exchange factors (GEFs). The BAR domain is crucial in maintaining yeast morphology and cellular localisation during infection. The data suggests that MsgA does not act as a canonical GEF during macrophage infection and identifies a temperature independent pathway in T. marneffei that controls intracellular yeast morphogenesis.

Highlights

BAR domain protein, MsgA, of Talaromyces marneffei regulates yeast morphogenesis during growth inside host cells Harshini Weerasinghe[1,2], Hayley E
RhoGEF proteins from a number of dimorphic and/or pathogenic fungi were examined and while orthologues of MsgA exist in many phyla they are absent from the Saccharomycotina sub-phylum and Basidiomycete phylum
In intracellular dimorphic pathogenic fungi, the ability to switch from a multicellular hyphal growth form into a unicellular yeast form that is more spatially suited to residing within host cells, is crucial for p athogenicity[1,3,4]

Summary

Introduction

BAR domain protein, MsgA, of Talaromyces marneffei regulates yeast morphogenesis during growth inside host cells Harshini Weerasinghe[1,2], Hayley E. This study describes a novel gene, msgA, from the dimorphic fungal pathogen Talaromyces marneffei that controls cell morphology in response to host cues rather than temperature. For many fungal pathogens that utilise the intracellular environment of macrophages as a means of immune system avoidance, morphological plasticity is an important virulence a ttribute[1,2,3,4,5,6]. This is exemplified by the dimorphic fungi, which display saprophytic, multicellular, filamentous hyphal growth in the external environment and are able to adopt a unicellular yeast growth form during infection. Once within the human host, T. marneffei conidia are engulfed by host primary alveolar macrophages where they bypass the process of arthroconidiation and germinate directly into yeast cells, which are the pathogenic

Methods

Results

Conclusion