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The putative polysaccharide synthase AfCps1 regulates Aspergillus fumigatus morphogenesis and conidia immune response in mouse bone marrow-derived macrophages

  • Microbial Physiology and Biochemistry
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Abstract

Aspergillus fumigatus is a well-known opportunistic pathogen that causes invasive aspergillosis (IA) infections with high mortality in immunosuppressed individuals. Morphogenesis, including hyphal growth, conidiation, and cell wall biosynthesis is crucial in A. fumigatus pathogenesis. Based on a previous random insertional mutagenesis library, we identified the putative polysaccharide synthase gene Afcps1 and its para-log Afcps2. Homologs of the cps gene are commonly found in the genomes of most fungal and some bacterial pathogens. Afcps1/cpsA is important in sporulation, cell wall composition, and virulence. However, the precise regulation patterns of cell wall integrity by Afcps1/cpsA and further effects on the immune response are poorly understood. Specifically, our in-depth study revealed that Afcps1 affects cell-wall stability, showing an increased resistance of ΔAfcps1 to the chitinmicrofibril destabilizing compound calcofluor white (CFW) and susceptibility of ΔAfcps1 to the β-(1,3)-glucan synthase inhibitor echinocandin caspofungin (CS). Additionally, deletion of Afcps2 had a normal sporulation phenotype but caused hypersensitivity to Na+ stress, CFW, and Congo red (CR). Specifically, quantitative analysis of cell wall composition using high-performance anion exchange chromatography-pulsed amperometric detector (HPAEC-PAD) analysis revealed that depletion of Afcps1 reduced cell wall glucan and chitin contents, which was consistent with the down-regulation of expression of the corresponding biosynthesis genes. Moreover, an elevated immune response stimulated by conidia of the ΔAfcps1 mutant in marrow-derived macrophages (BMMs) during phagocytosis was observed. Thus, our study provided new insights into the function of polysaccharide synthase Cps1, which is necessary for the maintenance of cell wall stability and the adaptation of conidia to the immune response of macrophages in A. fumigatus.

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Acknowledgments

This work was financially supported by the Natural Science Foundation of Zhejiang (LY19C010001), the National Natural Science Foundation of China (NSFC) (31500055 and 31901668), Scientific Research Fund of Zhejiang Provincial Education Department (Y201940932), the Natural Science Foundation of Ningbo (2019A610436), and School Research Project in Ningbo University (XYL19011). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, Huzhou University, Huzhou Central Hospital, Huzhou, P. R. China

    Sha Wang

  2. Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, P. R. China

    Anjie Yuan, Liping Zeng, Sikai Hou, Meng Wang, Lei Li & Guowei Zhong

  3. Key Laboratory of Animal Protein Deep Processing Technology of Zhejiang Province, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, 315800, P. R. China

    Zhendong Cai

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  1. Sha Wang
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Wang, S., Yuan, A., Zeng, L. et al. The putative polysaccharide synthase AfCps1 regulates Aspergillus fumigatus morphogenesis and conidia immune response in mouse bone marrow-derived macrophages. J Microbiol. 59, 64–75 (2021). https://doi.org/10.1007/s12275-021-0347-x

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