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

结核病(TB)是影响人类的最古老和最持久的细菌传染病之一。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武器库正在威胁着进一步扩大疾病负担。迫切需要新的治疗方法来抗击这种疾病。结核分枝杆菌(Mtb)是结核病的病原体，它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生存。一般来说，我们的白血球会吞噬并消化微生物以阻止感染，这一过程被称为吞噬作用。然而，结核病会产生许多物质，即“生存因子”，阻止这一过程，使细菌在白细胞内生长和繁殖，然后传播到附近的细胞。让细菌存活的确切机制仍然知之甚少。我们现在想知道这些生存因素是如何起作用的，以及当我们阻止他们的行动时会发生什么。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素的作用，与目前的抗生素相结合，有可能缩短治疗时间，提高对结核分枝杆菌敏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。

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.