Jesse Helen E, Roberts Ian S, Cavet Jennifer S
Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
Adv Microb Physiol. 2014;65:83-123. doi: 10.1016/bs.ampbs.2014.08.003. Epub 2014 Nov 4.
Listeria monocytogenes is responsible for one of the most life-threatening food-borne infections and the leading cause of food-poisoning associated deaths in the UK. Infection may be of the unborn/newly born infant where disease may manifest as listeric abortion, stillbirth or late-onset neonatal listeriosis, while in adults, infection usually affects the central nervous system causing meningitis. Crucial to the survival of L. monocytogenes, both inside and outside the host, is its ability to acquire metals which act as cofactors for a broad range of its cellular proteins. However, L. monocytogenes must also protect itself against the innate toxicity of metals. The importance of metals in host-pathogen interactions is illustrated by the restriction of metals (including zinc and iron) in vertebrates in response to infection and the use of high levels of metals (copper and zinc) as part of the antimicrobial defences within host phagocytes. As such, L. monocytogenes is equipped with various mechanisms to tightly control its cellular metal pools and avoid metal poisoning. These include multiple DNA-binding metal-responsive transcription factors, metal-acquisition, metal-detoxification and metal-storage systems, some of which represent key L. monocytogenes virulence determinants. This review discusses current knowledge of the role of metals in L. monocytogenes infections, with a focus on the mechanisms that contribute to zinc and copper homeostasis in this organism. The requirement to precisely control cellular metal levels may impose a vulnerability to L. monocytogenes which can be exploited in antimicrobials and therapeutics.
单核细胞增生李斯特菌是导致最具生命威胁的食源性感染之一的病原体，也是英国食物中毒相关死亡的主要原因。感染可能发生在未出生或新生儿身上，疾病表现为李斯特菌性流产、死产或迟发性新生儿李斯特菌病，而在成年人中，感染通常会影响中枢神经系统，导致脑膜炎。单核细胞增生李斯特菌在宿主内外生存的关键在于其获取金属的能力，这些金属作为其多种细胞蛋白的辅因子。然而，单核细胞增生李斯特菌还必须保护自身免受金属的内在毒性影响。金属在宿主 - 病原体相互作用中的重要性体现在脊椎动物在感染时对金属（包括锌和铁）的限制，以及宿主吞噬细胞内使用高水平金属（铜和锌）作为抗菌防御的一部分。因此，单核细胞增生李斯特菌具备各种机制来严格控制其细胞内金属池并避免金属中毒。这些机制包括多种DNA结合金属响应转录因子、金属获取、金属解毒和金属储存系统，其中一些代表了单核细胞增生李斯特菌的关键毒力决定因素。本综述讨论了目前关于金属在单核细胞增生李斯特菌感染中的作用的知识，重点关注该生物体中有助于锌和铜稳态的机制。精确控制细胞内金属水平的需求可能使单核细胞增生李斯特菌存在易损性，这可在抗菌药物和治疗中加以利用。
