Comparative analysis of cation-proton antiporters of NhaP type in Vibrio cholerae and Yersinia pestis

霍乱弧菌和鼠疫耶尔森氏菌NhaP型阳离子-质子逆向转运蛋白的比较分析

• 批准号: 227414-2012
• 负责人: Dibrov, Pavel
• 金额: $ 2.48万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=570269
• 关键词: Comparative; analysis; cation; proton; antiporters

Vibrio cholerae and Yersinia pestis are bacteria that cause the often-fatal diseases cholera and plague, which have a long grim history and still affect many millions of people, mostly in the developing countries of Asia, Africa and Latin America. In these dangerous human pathogens, virulence is strictly dependent on alkali/alkaline earth cations, primarily sodium and calcium. Therefore, investigation of sodium and calcium circulation in these pathogens is very important from both scientific and medical points of view. The sodium and calcium circulation in bacteria relies on specific membrane proteins called cation-proton antiporters. Cation-proton antiporters, responsible for the transport of Na+ and Ca2+, are important for bacterial virulence and thus should provide excellent targets for the development of novel antimicrobial agents to treat V. cholerae and Y. pestis infections. The membranes of both V. cholerae and Y. pestis contain cation-proton antiporters of a specific type, NhaP. Members of NhaP family of antiporters are known to be able to exchange protons for Ca2+ and/or Na+. While Y. pestis has only one such protein, Yp-NhaP, V. cholerae contains three NhaP isoforms, Vc-NhaP1, 2 and 3. Proposed research is focused on side-by-side biochemical and genetic characterization of these antiporters. Proposed studies will advance our understanding of the mechanisms and physiological impact of Na+ and Ca2+ circulation in V. cholerae and Y. pestis in relation to their pathogenicity and help to develop anti-bacterial remedies with novel mechanisms of action.

霍乱弧菌和鼠疫耶尔森氏菌是导致霍乱和鼠疫这种往往致命的疾病的细菌，霍乱和鼠疫有着漫长而严峻的历史，目前仍影响着数百万人，主要是在亚洲、非洲和拉丁美洲的发展中国家。在这些危险的人类病原体中，毒力严格依赖于碱/碱土阳离子，主要是钠和钙。因此，从科学和医学的角度研究这些病原菌的钠、钙循环是非常重要的。 细菌中的钠和钙循环依赖于被称为阳离子-质子逆向转运蛋白的特定膜蛋白。阳离子-质子逆向转运体负责Na+和Ca~(2+)的转运，对细菌的毒力具有重要作用，因此可以为开发治疗霍乱弧菌和鼠疫杆菌感染的新型抗菌剂提供良好的靶点。 霍乱弧菌和鼠疫杆菌的膜都含有一种特殊类型的阳离子-质子逆向转运蛋白NhaP。众所周知，NhaP家族的逆向转运蛋白能够用质子交换钙离子和/或钠离子。鼠疫耶尔森氏菌只有一种NhaP蛋白，而霍乱弧菌只有三种NhaP亚型，即VC-NhaP1、2和3。 所提出的研究将促进我们对霍乱弧菌和鼠疫耶尔森氏菌中Na+和Ca~(2+)循环与其致病性相关的机制和生理影响的理解，并有助于开发具有新作用机制的抗菌药物。