Department of Microbiology & Molecular Genetics, Michigan State University, East Lansing, Michigan, USA.
Infect Immun. 2023 Apr 18;91(4):e0044122. doi: 10.1128/iai.00441-22. Epub 2023 Mar 13.
To replicate within host cells, bacterial pathogens must acquire host-derived nutrients while avoiding degradative antimicrobial pathways. Fundamental insights into bacterial pathogenicity have been revealed by bacteria of the genus , which naturally parasitize free-living protozoa by establishing a membrane-bound replicative niche termed the -containing vacuole (LCV). Biogenesis of the LCV and intracellular replication rely on rapid evasion of the endocytic pathway and acquisition of host-derived nutrients, much of which is mediated by bacterial effector proteins translocated into host cells by a Dot/Icm type IV secretion system. Billions of years of co-evolution with eukaryotic hosts and broad host tropism have resulted in expansion of the genome to accommodate a massive repertoire of effector proteins that promote LCV biogenesis, safeguard the LCV from endolysosomal maturation, and mediate the acquisition of host nutrients. This minireview is focused on the mechanisms by which an ancient intracellular pathogen leverages effector proteins and hijacks host cell biology to obtain essential host-derived nutrients and prevent lysosomal degradation.
为了在宿主细胞内复制,细菌病原体必须获取宿主来源的营养物质,同时避免被宿主防御系统降解。通过自然寄生在自由生活的原生动物中的属的细菌,人们对细菌的致病性有了基本的了解,它们通过建立一个被膜包围的复制龛,称为含有 vacuole(LCV),来实现这一目标。LCV 的生物发生和细胞内复制依赖于快速逃避内吞途径和获取宿主来源的营养物质,其中大部分是由通过 Dot/Icm 型 IV 型分泌系统易位到宿主细胞的细菌效应蛋白介导的。与真核宿主数十亿年的共同进化和广泛的宿主嗜性导致了基因组的扩张,以容纳大量促进 LCV 生物发生、保护 LCV 免受内溶酶体成熟和介导宿主营养物质获取的效应蛋白。这篇小综述重点介绍了一种古老的细胞内病原体如何利用效应蛋白和劫持宿主细胞生物学来获取必需的宿主来源营养物质并防止溶酶体降解的机制。