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The putative polysaccharide synthase AfCps1 regulates Aspergillus fumigatus morphogenesis and conidia immune response in mouse bone marrow-derived macrophages
Sha Wang , Anjie Yuan , Liping Zeng , Sikai Hou , Meng Wang , Lei Li , Zhendong Cai , Guowei Zhong
J. Microbiol. 2021;59(1):64-75.   Published online November 17, 2020
DOI: https://doi.org/10.1007/s12275-021-0347-x
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  • 4 Web of Science
  • 3 Crossref
AbstractAbstract
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.

Citations

Citations to this article as recorded by  
  • Study on the metabolic changes and regulatory mechanism of Aspergillus flavus conidia germination
    Sifan Jia, Chong Li, Yu An, Desheng Qi, Erik F. Y. Hom
    Microbiology Spectrum.2024;[Epub]     CrossRef
  • Chitin Biosynthesis in Aspergillus Species
    Veronica S. Brauer, André M. Pessoni, Mateus S. Freitas, Marinaldo P. Cavalcanti-Neto, Laure N. A. Ries, Fausto Almeida
    Journal of Fungi.2023; 9(1): 89.     CrossRef
  • Evidencing New Roles for the Glycosyl-Transferase Cps1 in the Phytopathogenic Fungus Botrytis cinerea
    Matthieu Blandenet, Isabelle R. Gonçalves, Christine Rascle, Jean-William Dupuy, François-Xavier Gillet, Nathalie Poussereau, Mathias Choquer, Christophe Bruel
    Journal of Fungi.2022; 8(9): 899.     CrossRef
Research Support, Non-U.S. Gov't
Functional analysis of Vibrio vulnificus RND efflux pumps homologous to Vibrio cholerae VexAB and VexCD, and to Escherichia coli AcrAB
Seunghwa Lee , Ji-Hyun Yeom , Sojin Seo , Minho Lee , Sarang Kim , Jeehyeon Bae , Kangseok Lee , Jihwan Hwang
J. Microbiol. 2015;53(4):256-261.   Published online March 4, 2015
DOI: https://doi.org/10.1007/s12275-015-5037-0
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  • 9 Crossref
AbstractAbstract
Resistance-nodulation-division (RND) efflux pumps are associated with multidrug resistance in many gram-negative pathogens. The genome of Vibrio vulnificus encodes 11 putative RND pumps homologous to those of Vibrio cholerae and Escherichia coli. In this study, we analyzed three putative RND efflux pumps, showing homology to V. cholerae VexAB and VexCD and to E. coli AcrAB, for their functional roles in multidrug resistance of V. vulnificus. Deletion of the vexAB homolog resulted in increased susceptibility of V. vulnificus to bile acid, acriflavine, ethidium bromide, and erythromycin, whereas deletion of acrAB homologs rendered V. vulnificus more susceptible to acriflavine only. Deletion of vexCD had no effect on susceptibility of V. vulnificus to these chemicals. Upon exposure to these antibacterial chemicals, expression of tolCV1 and tolCV2, which are putative outer membrane factors of RND efflux pumps, was induced, whereas expression levels of vexAB, vexCD, and acrAB homologs were not significantly changed. Our results show that the V. vulnificus homologs of VexAB largely contributed to in vitro antimicrobial resistance with a broad substrate specificity that was partially redundant with the AcrAB pump homologs.

Citations

Citations to this article as recorded by  
  • Dynamics of efflux pumps in antimicrobial resistance, persistence, and community living of Vibrionaceae
    Sanath Kumar, Manjusha Lekshmi, Jerusha Stephen, Anely Ortiz-Alegria, Matthew Ayitah, Manuel F. Varela
    Archives of Microbiology.2024;[Epub]     CrossRef
  • Membrane Efflux Pumps of Pathogenic Vibrio Species: Role in Antimicrobial Resistance and Virulence
    Jerusha Stephen, Manjusha Lekshmi, Parvathi Ammini, Sanath H. Kumar, Manuel F. Varela
    Microorganisms.2022; 10(2): 382.     CrossRef
  • TolCV1 Has Multifaceted Roles During Vibrio vulnificus Infection
    Yue Gong, Rui Hong Guo, Joon Haeng Rhee, Young Ran Kim
    Frontiers in Cellular and Infection Microbiology.2021;[Epub]     CrossRef
  • The mechanisms that regulate Vibrio parahaemolyticus virulence gene expression differ between pathotypes
    Nicholas Petronella, Jennifer Ronholm
    Microbial Genomics .2018;[Epub]     CrossRef
  • ATP-Binding Cassette Transporter VcaM from Vibrio cholerae is Dependent on the Outer Membrane Factor Family for Its Function
    Wen-Jung Lu, Hsuan-Ju Lin, Thamarai Janganan, Cheng-Yi Li, Wei-Chiang Chin, Vassiliy Bavro, Hong-Ting Lin
    International Journal of Molecular Sciences.2018; 19(4): 1000.     CrossRef
  • Contribution of efflux systems to the detergent resistance, cytotoxicity, and biofilm formation of Vibrio vulnificus
    Chung-Cheng Lo, Pei-Ting Lin, Chuan Chiang-Ni, Kuan-Hua Lin, Shin-Luen Lee, Tzu-Fang Kuo, Horng-Ren Lo
    Gene Reports.2017; 9: 115.     CrossRef
  • Survival of the Fittest: How Bacterial Pathogens Utilize Bile To Enhance Infection
    Jeticia R. Sistrunk, Kourtney P. Nickerson, Rachael B. Chanin, David A. Rasko, Christina S. Faherty
    Clinical Microbiology Reviews.2016; 29(4): 819.     CrossRef
  • MdsABC-Mediated Pathway for Pathogenicity in Salmonella enterica Serovar Typhimurium
    Saemee Song, Boeun Lee, Ji-Hyun Yeom, Soonhye Hwang, Ilnam Kang, Jang-Cheon Cho, Nam-Chul Ha, Jeehyeon Bae, Kangseok Lee, Yong-Hak Kim, S. M. Payne
    Infection and Immunity.2015; 83(11): 4266.     CrossRef
  • Molecular architecture of the bacterial tripartite multidrug efflux pump focusing on the adaptor bridging model
    Saemee Song, Jin-Sik Kim, Kangseok Lee, Nam-Chul Ha
    Journal of Microbiology.2015; 53(6): 355.     CrossRef

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