Title |
The putative polysaccharide synthase AfCps1 regulates Aspergillus fumigatus morphogenesis and conidia immune response in mouse bone marrow-derived macrophages |
Author |
Sha Wang1, Anjie Yuan2, Liping Zeng2, Sikai Hou2, Meng Wang2, Lei Li2, Zhendong Cai3*, and Guowei Zhong2* |
Address |
1Key Laboratory of Vector Biology and Pathogen Control of Zhejiang Province, Huzhou University, Huzhou Central Hospital, P. R. China, 2Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing 211166, P. R. China, 3Key Laboratory of Animal Protein Deep Processing Technology of Zhejiang Province, College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo 315800, P. R. China |
Bibliography |
Journal of Microbiology, 59(1),64–75, 2021,
|
DOI |
10.1007/s12275-021-0347-x
|
Key Words |
Aspergillus fumigatus, polysaccharide synthase,
cell wall integrity, bone marrow macrophages, immune activation |
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 paralog
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 downregulation
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. |