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源自 - 的头孢菌素酶基因的分子进化分析。

Molecular Evolutionary Analyses of the -Derived Cephalosporinase Gene.

作者信息

Shirai Tatsuya, Akagawa Mao, Makino Miho, Ishii Manami, Arai Ayaka, Nagasawa Norika, Sada Mitsuru, Kimura Ryusuke, Okayama Kaori, Ishioka Taisei, Ishii Haruyuki, Hirai Shinichiro, Ryo Akihide, Tomita Haruyoshi, Kimura Hirokazu

机构信息

Advanced Medical Science Research Center, Gunma Paz University Research Institute, Shibukawa 377-0008, Gunma, Japan.

Department of Respiratory Medicine, Kyorin University School of Medicine, Mitaka 181-8611, Tokyo, Japan.

出版信息

Microorganisms. 2023 Mar 1;11(3):635. doi: 10.3390/microorganisms11030635.

Abstract

Despite the increasing evidence of the clinical impact of -derived cephalosporinase (PDC) sequence polymorphisms, the molecular evolution of its encoding gene, , remains elusive. To elucidate this, we performed a comprehensive evolutionary analysis of . A Bayesian Markov Chain Monte Carlo phylogenetic tree revealed that a common ancestor of diverged approximately 4660 years ago, leading to the formation of eight clonal variants (clusters A-H). The phylogenetic distances within clusters A to G were short, whereas those within cluster H were relatively long. Two positive selection sites and many negative selection sites were estimated. Two PDC active sites overlapped with negative selection sites. In docking simulation models based on samples selected from clusters A and H, piperacillin was bound to the serine and the threonine residues of the PDC active sites, with the same binding mode for both models. These results suggest that, in , is highly conserved, and PDC exhibits similar antibiotic resistance functionality regardless of its genotype.

摘要

尽管越来越多的证据表明源自头孢菌素酶(PDC)序列多态性的临床影响,但其编码基因的分子进化仍不清楚。为了阐明这一点,我们对进行了全面的进化分析。贝叶斯马尔可夫链蒙特卡罗系统发育树显示,的一个共同祖先大约在4660年前分化,导致形成八个克隆变体(A-H簇)。A到G簇内的系统发育距离较短,而H簇内的距离相对较长。估计有两个正选择位点和许多负选择位点。两个PDC活性位点与负选择位点重叠。在基于从A和H簇中选择的样本的对接模拟模型中,哌拉西林与PDC活性位点的丝氨酸和苏氨酸残基结合,两个模型的结合模式相同。这些结果表明,在中,高度保守,并且无论其基因型如何,PDC都表现出相似的抗生素抗性功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f3e/10057138/fd5f5715de65/microorganisms-11-00635-g001.jpg

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