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Ynt is the primary nickel import system used by Proteus mirabilis and specifically contributes to fitness by supplying nickel for urease activity.
Molecular Microbiology ( IF 2.6 ) Pub Date : 2020-04-07 , DOI: 10.1111/mmi.14505
Aimee L Brauer 1 , Brian S Learman 1 , Chelsie E Armbruster 1
Affiliation  

Proteus mirabilis is a Gram‐negative uropathogen and frequent cause of catheter‐associated urinary tract infection (CAUTI). One important virulence factor is its urease enzyme, which requires nickel to be catalytically active. It is, therefore, hypothesized that nickel import is critical for P. mirabilis urease activity and pathogenesis during infection. P. mirabilis strain HI4320 encodes two putative nickel import systems, designated Nik and Ynt. By disrupting the substrate‐binding proteins from each import system (nikA and yntA), we show that Ynt is the primary nickel importer, while Nik only compensates for loss of Ynt at high nickel concentrations. We further demonstrate that these are the only binding proteins capable of importing nickel for incorporation into the urease enzyme. Loss of either nickel‐binding protein results in a significant fitness defect in a murine model of CAUTI, but YntA is more crucial as the yntA mutant was significantly outcompeted by the nikA mutant. Furthermore, despite the importance of nickel transport for hydrogenase activity, the sole contribution of yntA and nikA to virulence is due to their role in urease activity, as neither mutant exhibited a fitness defect when disrupted in a urease‐negative background.

中文翻译:

Ynt 是奇异变形杆菌使用的主要镍进口系统,通过为尿素酶活性提供镍来特别有助于健康。

奇异变形杆菌是一种革兰氏阴性尿路病原体,是导尿管相关尿路感染 (CAUTI) 的常见原因。一种重要的毒力因子是其脲酶,它需要镍具有催化活性。因此,假设镍的输入对于奇异假单胞菌脲酶活性和感染过程中的发病机制至关重要。P. mirabilis菌株 HI4320 编码两个假定的镍输入系统,指定为 Nik 和 Ynt。通过破坏来自每个输入系统(nikAyntA)的底物结合蛋白),我们表明 Ynt 是主要的镍进口国,而 Nik 仅补偿高镍浓度下 Ynt 的损失。我们进一步证明,这些是唯一能够导入镍以掺入脲酶的结合蛋白。在 CAUTI 小鼠模型中,任一镍结合蛋白的缺失都会导致显着的适应性缺陷,但 YntA 更为重要,因为yntA突变体明显被nikA突变体击败。此外,尽管镍转运对氢化酶活性很重要,但yntAnikA对毒力的唯一贡献是由于它们在脲酶活性中的作用,因为当在脲酶阴性背景下被破坏时,这两个突变体都没有表现出适应性缺陷。
更新日期:2020-04-07
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