マダニが媒介する病気を防ぐ鍵となるタンパク質を発見(Protein found that may hold key to preventing a tick-borne disease)

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2023-09-27 ワシントン州立大学(WSU)

◆ワシントン州立大学の研究者は、アナプラズモーシスと呼ばれる病気を引き起こす有害な細菌が、ノミマダニに定着し、ヒトホストに伝播するプロセスにおいて重要な役割を果たすタンパク質を特定しました。
◆この研究により、ノミマダニ内での細菌の生存と拡散のメカニズムが理解され、他のノミマダニ媒介疾患の予防戦略の可能性が開かれました。
◆研究者は、このタンパク質をブロックする方法を開発し、ノミマダニからの細菌伝播を防ぐ方法を探ることができるかもしれないと述べています。アナプラズモーシスはノミマダニによって伝えられ、アメリカ合衆国での症例は増加しています。

<関連情報>

Anaplasma phagocytophilum T4SSエフェクターAteAがマダニ感染に必須であることを発見 An Anaplasma phagocytophilum T4SS effector, AteA, is essential for tick infection

Jason M. Park, Brittany M. Genera, Deirdre Fahy, Kyle T. Swallow, Curtis M. Nelson, Jonathan D. Oliver, Dana K. Shaw, Ulrike G. Munderloh, Kelly A. Brayton
mBio  Published:25 September 2023
DOI:https://doi.org/10.1128/mbio.01711-23

ABSTRACT

Pathogens must adapt to disparate environments in permissive host species, a feat that is especially pronounced for vector-borne microbes, which transition between vertebrate hosts and arthropod vectors to complete their lifecycles. Most knowledge about arthropod-vectored bacterial pathogens centers on their life in the mammalian host, where disease occurs. However, disease outbreaks are driven by the arthropod vectors. Adapting to the arthropod is critical for obligate intracellular rickettsial pathogens, as they depend on eukaryotic cells for survival. To manipulate the intracellular environment, these bacteria use type IV secretion systems (T4SS) to deliver effectors into the host cell. To date, few rickettsial T4SS translocated effectors have been identified and have only been examined in the context of mammalian infection. We identified an effector from the tick-borne rickettsial pathogen Anaplasma phagocytophilum, HGE1_02492, as critical for survival in tick cells and acquisition by ticks in vivo. Conversely, HGE1_02492 was dispensable during mammalian cell culture and murine infection. We show that HGE1_02492 is translocatable in a T4SS-dependent manner to the host cell cytosol. In eukaryotic cells, the HGE1_02492 localized with cortical actin filaments, which is dependent on multiple sub-domains of the protein. HGE1_02492 is the first arthropod-vector specific T4SS translocated effector identified from a rickettsial pathogen. Moreover, the subcellular target of HGE1_02492 suggests that A. phagocytophilum is manipulating actin to enable arthropod colonization. Based on these findings, we propose the name AteA for Anaplasma (phagocytophilum) tick effector A. Altogether, we show that A. phagocytophilum uses distinct strategies to cycle between mammals and arthropods.

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