Elucidating the role of mycobacterial secreted phosphatases in host lipid dynamics and pathogen survival

阐明分枝杆菌分泌磷酸酶在宿主脂质动态和病原体存活中的作用

• 批准号: BB/T00083X/1
• 负责人: Lydia Tabernero
• 金额: $ 50.36万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FT00083X%2F1
• 关键词: Elucidating; role; mycobacterial; secreted; phosphatases

Tuberculosis (TB) is one of the oldest and most persistent bacterial infectious diseases that affects humans. Despite significant advances to control the spread of TB with the introduction of vaccines and antibiotics, one third of the human population is still infected, and 1.6 million die every year. The rise in drug resistance and the limited arsenal of effective antibiotics is threatening to further expand the disease burden. New therapeutic approaches are urgently needed to fight the disease. Mycobacterium tuberculosis (Mtb), the causing agent of TB, is able to challenge our immune system and to survive in the lungs by evading our natural defences. Generally, our white blood cells will engulf and digest microbes to stop infections, in a process known as phagocytosis. However, TB produces a number of substances, "survival factors", that stop this process allowing the bacteria to grow and multiply inside the white blood cells and then spread to nearby cells. The precise mechanisms that allow the bacteria to survive are still poorly understood. We now want to understand how these survival factors work and what happens when we block their action. A better understanding of these processes will help us to develop new strategies to treat TB and other infectious diseases, leading to the development of new types of medicines to eliminate bacteria. Blocking the action of these essential survival factors, in combination with current antibiotics, has the potential to shorten the time of treatment, increase efficacy against susceptible and drug resistant strains of Mtb, thereby increasing cure rates, and preventing relapse in patients with an impaired inmune system.

结核病（TB）是影响人类的最古老和最持久的细菌性传染病之一。尽管随着疫苗和抗生素的引入，在控制结核病传播方面取得了重大进展，但仍有三分之一的人口受到感染，每年有160万人死亡。耐药性的上升和有效抗生素的有限可能会进一步扩大疾病负担。迫切需要新的治疗方法来对抗这种疾病。结核病的病原体结核分枝杆菌（Mtb）能够挑战我们的免疫系统，并通过逃避我们的自然防御在肺部存活。一般来说，我们的白细胞会吞噬和消化微生物来阻止感染，这一过程被称为吞噬作用。然而，结核病会产生一些物质，即“生存因子”，阻止这一过程，使细菌在白细胞内生长和繁殖，然后扩散到附近的细胞。让细菌存活的确切机制仍然知之甚少。我们现在想了解这些生存因素是如何工作的，以及当我们阻止它们的作用时会发生什么。更好地了解这些过程将有助于我们制定治疗结核病和其他传染病的新战略，从而开发出消除细菌的新型药物。阻断这些基本生存因子的作用，与现有抗生素联合使用，有可能缩短治疗时间，提高对结核分枝杆菌易感和耐药菌株的疗效，从而提高治愈率，并防止免疫系统受损患者的复发。

项目成果

Discovery of uncompetitive inhibitors of SapM that compromise intracellular survival of Mycobacterium tuberculosis.

• DOI: 10.1038/s41598-021-87117-x
• 发表时间: 2021-04-07
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Fernández-Soto P;Casulli J;Solano-Castro D;Rodríguez-Fernández P;Jowitt TA;Travis MA;Cavet JS;Tabernero L
• 通讯作者: Tabernero L

Impact of diesel exhaust particles on infections with Mycobacterium bovis BCG in in vitro human macrophages and an in vivo Galleria mellonella model.

• DOI: 10.1016/j.envpol.2023.122597
• 发表时间: 2024-01-15
• 期刊: ENVIRONMENTAL POLLUTION
• 影响因子: 8.9
• 作者: Rodriguez-Fernandez, Pablo;Romero-Andrada, Iris;Molina-Moya, Barbara;Latorre, Irene;Lacoma, Alicia;Prat-Aymerich, Cristina;Tabernero, Lydia;Dominguez, Jose
• 通讯作者: Dominguez, Jose