<p>Nucleotide biosynthesis pathways in organisms are widely&#xa0;utilized in the development of antineoplastic and antifungal drugs in medical field. However, little was known about the catalytic enzymes in the pyrimidine salvage pathway of <i>Phytophthora capsici</i>, a major oomycete pathogen responsible for horticultural crop blight disease around the world. In current study, the functional characteristics of uridine kinase PcUK in the pyrimidine salvage pathway of <i>P. capsici</i>, as well as the effect of nucleoside drugs 5-Fluorouridine (5-FD), 5-Fluorouracil (5-FU), and 5-Flucytosine (5-FC) on <i>Phytophthora</i> pathogens were investigated. We demonstrate that 5-FD, 5-FU, and 5-FC could strongly inhibit the growth of <i>P. capsici</i> and <i>P. sojae</i>, in which&#xa0;the inhibition effect of 5-FD and 5-FU was dependent on the presence of PcUK. Moreover, PcUK is mainly localized at endoplasmic reticulum, and it could form homomeric complex and interact with Kelch⁃like protein Pc028643. Although uridine kinases across various <i>Phytophthora</i> species are highly conserved, neither deleting nor overexpressing <i>PcUK</i> could affect the growth and pathogenicity of <i>P. capsici</i>. Taken together, these results identified and characterized the uridine kinase PcUK in <i>P. capsici</i>, highlighting that PcUK is mainly localized at endoplasmic reticulum and its essential role in the inhibition of <i>P. capsici</i> by 5-FD and 5-FU.</p>

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The uridine kinase PcUK is essential for the inhibition of Phytophthora capsici by 5-Fluorouridine and 5-Fluorouracil

  • Jing-Hao Jin,
  • Xin-Xin Chen,
  • Chang-Shuai Wang,
  • Shi-Chao Sun,
  • Chao Su,
  • Xiao-Ren Chen

摘要

Nucleotide biosynthesis pathways in organisms are widely utilized in the development of antineoplastic and antifungal drugs in medical field. However, little was known about the catalytic enzymes in the pyrimidine salvage pathway of Phytophthora capsici, a major oomycete pathogen responsible for horticultural crop blight disease around the world. In current study, the functional characteristics of uridine kinase PcUK in the pyrimidine salvage pathway of P. capsici, as well as the effect of nucleoside drugs 5-Fluorouridine (5-FD), 5-Fluorouracil (5-FU), and 5-Flucytosine (5-FC) on Phytophthora pathogens were investigated. We demonstrate that 5-FD, 5-FU, and 5-FC could strongly inhibit the growth of P. capsici and P. sojae, in which the inhibition effect of 5-FD and 5-FU was dependent on the presence of PcUK. Moreover, PcUK is mainly localized at endoplasmic reticulum, and it could form homomeric complex and interact with Kelch⁃like protein Pc028643. Although uridine kinases across various Phytophthora species are highly conserved, neither deleting nor overexpressing PcUK could affect the growth and pathogenicity of P. capsici. Taken together, these results identified and characterized the uridine kinase PcUK in P. capsici, highlighting that PcUK is mainly localized at endoplasmic reticulum and its essential role in the inhibition of P. capsici by 5-FD and 5-FU.