The Gβ-like Protein AfCpcB Affects Sexual Development, Response to Oxidative Stress and Phagocytosis by Alveolar Macrophages in Aspergillus fumigatus.

Joo-Yeon Lim,Yeon-Ju Kim,Hee-Moon Park

doi:10.3390/jof8010056

Joo-Yeon Lim, Yeon-Ju Kim + Show 1 more

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https://doi.org/10.3390/jof8010056

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Abstract

G-protein signaling is important for signal transduction, allowing various stimuli that are external to a cell to affect its internal molecules. In Aspergillus fumigatus, the roles of Gβ-like protein CpcB on growth, asexual development, drug sensitivity, and virulence in a mouse model have been previously reported. To gain a deeper insight into Aspergillus fumigatus sexual development, the ΔAfcpcB strain was generated using the supermater AFB62 strain and crossed with AFIR928. This cross yields a decreased number of cleistothecia, including few ascospores. The sexual reproductive organ-specific transcriptional analysis using RNAs from the cleistothecia (sexual fruiting bodies) indicated that the CpcB is essential for the completion of sexual development by regulating the transcription of sexual genes, such as veA, steA, and vosA. The ΔAfcpcB strain revealed increased resistance to oxidative stress by regulating genes for catalase, peroxiredoxin, and ergosterol biosynthesis. The ΔAfcpcB strain showed decreased uptake by alveolar macrophages in vitro, decreased sensitivity to Congo red, decreased expression of cell wall genes, and increased expression of the hydrophobin genes. Taken together, these findings indicate that AfCpcB plays important roles in sexual development, phagocytosis by alveolar macrophages, biosynthesis of the cell wall, and oxidative stress response.

Highlights

Aspergillus fumigatus is found in indoor air, household dust, and outdoor environments, including soil and plant matter [1]
These results suggested that the AfcpcB strain causes a possible change in both inner and outer cell wall layers, affecting the capacity of pattern recognition receptors (PRR) in host immune cells to react with the A. fumigatus conidia surface
CpcB was found to be required for vegetative growth, germination, asexAlthough CpcB was found to be required for vegetative growth, germination, asexual ual development, and gliotoxin production in A. fumigatus [8] and growth and developdevelopment, and gliotoxin production in A. fumigatus [8] and growth and development ment of A. nidulans [11], the cpcB deletion in the A. fumigatus supermater strain showed of A. nidulans [11], the cpcB deletion in the A. fumigatus supermater strain showed no signo significant change in vegetative growth and asexual development

Summary

Introduction

Aspergillus fumigatus is found in indoor air, household dust, and outdoor environments, including soil and plant matter [1]. Fungal spores of A. fumigatus account for large proportions of air and can be inhaled deep into the lungs, resulting in health problems. Conidia are small enough (2–3 μm in diameter) to reach the human pulmonary alveoli [2,3]. The opportunistic fungal pathogen, A. fumigatus, is a leading agent of aspergillosis [4]. The inhaled A. fumigatus conidia can cause invasive aspergillosis in immunocompromised hosts [5]. The incidence of fungal infections has steadily increased and has become an emerging focus in recent decades [6]

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