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

Research output: Contribution to journalArticlepeer-review


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 effectorsinto the host cell. To date, few rickettsial T4SS translocated effectorshave been identifiedand have only been examined in the context of mammalian infection. We identifiedan effectorfrom 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 firstarthropod-vector specificT4SS translocated effectoridentifiedfrom 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 effectorA. Altogether, we show that A. phagocytophilum uses distinct strategies to cycle between mammals and arthropods. IMPORTANCE Ticks are the number one vector of pathogens for livestock worldwide and for humans in the United States. The biology of tick transmission is an understudied area. Understanding this critical interaction could provide opportunities to affectthe course of disease spread. In this study, we examined the zoonotic tick-borne agent Anaplasma phagocytophilum and identifieda secreted protein, AteA, which is expressed in a tick-specificmanner. These secreted proteins, termed effectors,are the firstproteins to interact with the host environment. AteA is essential for survival in ticks and appears to interact with cortical actin. Most effectorproteins are studied in the context of the mammalian host; however, understanding how this unique set of proteins affectstick transmission is critical to developing interventions.

Original languageEnglish (US)
Issue number5
StatePublished - 2023

Bibliographical note

Publisher Copyright:
© 2023 American Society for Microbiology. All rights reserved.


  • actin
  • Anaplasma
  • effectorfunctions
  • host-pathogen interactions
  • obligate intracellular
  • rickettsia
  • vector-borne diseases

PubMed: MeSH publication types

  • Journal Article


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