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Carbonic Anhydrase from Porphyromonas Gingivalis as a Drug Target

机译:牙龈卟啉单胞菌的碳酸酐酶为药物靶标

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Periodontitis originates from a microbial synergy causing the development of a mouth microbial imbalance (dysbiosis), consisting of a microbial community composed of anaerobic bacteria. Most studies concerning the treatment of periodontitis have primarily take into account the Gram-negative bacterium Porphyromonas gingivalis , because it is a prominent component of the oral microbiome and a successful colonizer of the oral epithelium. Here, we focus our attention on the study of the carbonic anhydrases (CAs, EC 4.2.1.1) encoded in the genome of this pathogen as a possible drug target. Carbonic anhydrases are a superfamily of metalloenzymes, which catalyze the simple but physiologically crucial reaction of carbon dioxide hydration to bicarbonate and protons. Bacterial CAs have attracted significant attention for affecting the survival, invasion, and pathogenicity of many microorganisms. The P. gingivalis genome encodes for two CAs belonging to β-CA (PgiCAβ) and γ-CA (PgiCAγ) families. These two enzymes were cloned, heterologously expressed in Escherichia coli , and purified to homogeneity. Moreover, they were subject to extensive inhibition studies using the classical CA inhibitors (sulfonamides and anions) with the aim of identifying selective inhibitors of PgiCAβ and PgiCAγ to be used as pharmacological tools for P. gingivalis eradication.
机译:牙周炎起源于微生物协同作用,引起口腔微生物失衡(营养不良)的发展,该疾病由厌氧细菌组成的微生物群落组成。大多数有关牙周炎治疗的研究都主要考虑了革兰氏阴性细菌牙龈卟啉单胞菌,因为它是口腔微生物组的重要组成部分,是口腔上皮细胞的成功定居者。在这里,我们将注意力集中在研究这种病原体的基因组中编码的碳酸酐酶(CAs,EC 4.2.1.1)作为可能的药物靶标。碳酸酐酶是金属酶的超家族,其催化二氧化碳水合为碳酸氢根和质子的简单但对生理至关重要的反应。细菌CA对影响许多微生物的存活,侵袭和致病性引起了极大的关注。牙龈卟啉单胞菌基因组编码属于β-CA(PgiCAβ)和γ-CA(PgiCAγ)家族的两个CA。克隆这两种酶,在大肠杆菌中异源表达,并纯化至同质。此外,他们还使用经典的CA抑制剂(磺酰胺和阴离子)进行了广泛的抑制研究,目的是鉴定PgiCAβ和PgiCAγ的选择性抑制剂,以用作根除牙龈卟啉单胞菌的药理学工具。

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