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Chitin deacetylases Cod4 and Cod7 are involved in polar growth of Aspergillus fumigatus

Chitin is one of the key components of fungal cell wall, and chitin deacetylases (CDAs) have been found in fungi; however, their functions remain unknown. Aspergillus fumigatus is known to cause fatal invasive aspergillosis (IA) among immunocompromised patients with a high mortality rate. Although t...

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Autores principales: Xie, Mingming, Zhao, Xiaobing, Lü, Yang, Jin, Cheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957412/
https://www.ncbi.nlm.nih.gov/pubmed/31602821
http://dx.doi.org/10.1002/mbo3.943
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author Xie, Mingming
Zhao, Xiaobing
Lü, Yang
Jin, Cheng
author_facet Xie, Mingming
Zhao, Xiaobing
Lü, Yang
Jin, Cheng
author_sort Xie, Mingming
collection PubMed
description Chitin is one of the key components of fungal cell wall, and chitin deacetylases (CDAs) have been found in fungi; however, their functions remain unknown. Aspergillus fumigatus is known to cause fatal invasive aspergillosis (IA) among immunocompromised patients with a high mortality rate. Although the A. fumigatus cell wall has long been taken as a unique target for drug development, its dynamic remodeling is complicated and not well understood. Seven putative CDAs are annotated in the A. fumigatus genome. In this study, we analyzed the function of the putative CDAs, Cod4 and Cod7, in A. fumigatus. Biochemical analysis of recombinant proteins showed that Cod4 preferentially deacetylated (GlcNAc)(4) and was less active on chitooligosaccharides with DP > 5, whereas Cod7 was unable to catalyze deacetylation. Simulation of three‐dimensional structure revealed that both Cod4 and Cod7 shared a similar folding pattern with HyPgdA from Helicobacter pylori and, similar to HyPgdA, a substitution of Thr8 by Ala8 in Cod7 abolished its CDA activity. Deletion of the cod4, cod7, or both in A. fumigatus led to polarity abnormality and increased conidiation. Furthermore, the expression level of the genes related to polarity was upregulated in the mutants. Our results demonstrated that Cod4 and Cod7 were involved in polarity, though Cod4 was inactive.
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spelling pubmed-69574122020-01-17 Chitin deacetylases Cod4 and Cod7 are involved in polar growth of Aspergillus fumigatus Xie, Mingming Zhao, Xiaobing Lü, Yang Jin, Cheng Microbiologyopen Original Articles Chitin is one of the key components of fungal cell wall, and chitin deacetylases (CDAs) have been found in fungi; however, their functions remain unknown. Aspergillus fumigatus is known to cause fatal invasive aspergillosis (IA) among immunocompromised patients with a high mortality rate. Although the A. fumigatus cell wall has long been taken as a unique target for drug development, its dynamic remodeling is complicated and not well understood. Seven putative CDAs are annotated in the A. fumigatus genome. In this study, we analyzed the function of the putative CDAs, Cod4 and Cod7, in A. fumigatus. Biochemical analysis of recombinant proteins showed that Cod4 preferentially deacetylated (GlcNAc)(4) and was less active on chitooligosaccharides with DP > 5, whereas Cod7 was unable to catalyze deacetylation. Simulation of three‐dimensional structure revealed that both Cod4 and Cod7 shared a similar folding pattern with HyPgdA from Helicobacter pylori and, similar to HyPgdA, a substitution of Thr8 by Ala8 in Cod7 abolished its CDA activity. Deletion of the cod4, cod7, or both in A. fumigatus led to polarity abnormality and increased conidiation. Furthermore, the expression level of the genes related to polarity was upregulated in the mutants. Our results demonstrated that Cod4 and Cod7 were involved in polarity, though Cod4 was inactive. John Wiley and Sons Inc. 2019-10-11 /pmc/articles/PMC6957412/ /pubmed/31602821 http://dx.doi.org/10.1002/mbo3.943 Text en © 2019 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Xie, Mingming
Zhao, Xiaobing
Lü, Yang
Jin, Cheng
Chitin deacetylases Cod4 and Cod7 are involved in polar growth of Aspergillus fumigatus
title Chitin deacetylases Cod4 and Cod7 are involved in polar growth of Aspergillus fumigatus
title_full Chitin deacetylases Cod4 and Cod7 are involved in polar growth of Aspergillus fumigatus
title_fullStr Chitin deacetylases Cod4 and Cod7 are involved in polar growth of Aspergillus fumigatus
title_full_unstemmed Chitin deacetylases Cod4 and Cod7 are involved in polar growth of Aspergillus fumigatus
title_short Chitin deacetylases Cod4 and Cod7 are involved in polar growth of Aspergillus fumigatus
title_sort chitin deacetylases cod4 and cod7 are involved in polar growth of aspergillus fumigatus
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957412/
https://www.ncbi.nlm.nih.gov/pubmed/31602821
http://dx.doi.org/10.1002/mbo3.943
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