Cargando…

An Anaplasma phagocytophilum T4SS effector, AteA, is essential for tick infection

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Park, Jason M., Genera, Brittany M., Fahy, Deirdre, Swallow, Kyle T., Nelson, Curtis M., Oliver, Jonathan D., Shaw, Dana K., Munderloh, Ulrike G., Brayton, Kelly A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10653876/
https://www.ncbi.nlm.nih.gov/pubmed/37747883
http://dx.doi.org/10.1128/mbio.01711-23
_version_ 1785136507468644352
author Park, Jason M.
Genera, Brittany M.
Fahy, Deirdre
Swallow, Kyle T.
Nelson, Curtis M.
Oliver, Jonathan D.
Shaw, Dana K.
Munderloh, Ulrike G.
Brayton, Kelly A.
author_facet Park, Jason M.
Genera, Brittany M.
Fahy, Deirdre
Swallow, Kyle T.
Nelson, Curtis M.
Oliver, Jonathan D.
Shaw, Dana K.
Munderloh, Ulrike G.
Brayton, Kelly A.
author_sort Park, Jason M.
collection PubMed
description 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. 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 affect the course of disease spread. In this study, we examined the zoonotic tick-borne agent Anaplasma phagocytophilum and identified a secreted protein, AteA, which is expressed in a tick-specific manner. These secreted proteins, termed effectors, are the first proteins to interact with the host environment. AteA is essential for survival in ticks and appears to interact with cortical actin. Most effector proteins are studied in the context of the mammalian host; however, understanding how this unique set of proteins affects tick transmission is critical to developing interventions.
format Online
Article
Text
id pubmed-10653876
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher American Society for Microbiology
record_format MEDLINE/PubMed
spelling pubmed-106538762023-09-25 An Anaplasma phagocytophilum T4SS effector, AteA, is essential for tick infection Park, Jason M. Genera, Brittany M. Fahy, Deirdre Swallow, Kyle T. Nelson, Curtis M. Oliver, Jonathan D. Shaw, Dana K. Munderloh, Ulrike G. Brayton, Kelly A. mBio Research Article 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. 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 affect the course of disease spread. In this study, we examined the zoonotic tick-borne agent Anaplasma phagocytophilum and identified a secreted protein, AteA, which is expressed in a tick-specific manner. These secreted proteins, termed effectors, are the first proteins to interact with the host environment. AteA is essential for survival in ticks and appears to interact with cortical actin. Most effector proteins are studied in the context of the mammalian host; however, understanding how this unique set of proteins affects tick transmission is critical to developing interventions. American Society for Microbiology 2023-09-25 /pmc/articles/PMC10653876/ /pubmed/37747883 http://dx.doi.org/10.1128/mbio.01711-23 Text en Copyright © 2023 Park et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Park, Jason M.
Genera, Brittany M.
Fahy, Deirdre
Swallow, Kyle T.
Nelson, Curtis M.
Oliver, Jonathan D.
Shaw, Dana K.
Munderloh, Ulrike G.
Brayton, Kelly A.
An Anaplasma phagocytophilum T4SS effector, AteA, is essential for tick infection
title An Anaplasma phagocytophilum T4SS effector, AteA, is essential for tick infection
title_full An Anaplasma phagocytophilum T4SS effector, AteA, is essential for tick infection
title_fullStr An Anaplasma phagocytophilum T4SS effector, AteA, is essential for tick infection
title_full_unstemmed An Anaplasma phagocytophilum T4SS effector, AteA, is essential for tick infection
title_short An Anaplasma phagocytophilum T4SS effector, AteA, is essential for tick infection
title_sort anaplasma phagocytophilum t4ss effector, atea, is essential for tick infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10653876/
https://www.ncbi.nlm.nih.gov/pubmed/37747883
http://dx.doi.org/10.1128/mbio.01711-23
work_keys_str_mv AT parkjasonm ananaplasmaphagocytophilumt4sseffectorateaisessentialfortickinfection
AT generabrittanym ananaplasmaphagocytophilumt4sseffectorateaisessentialfortickinfection
AT fahydeirdre ananaplasmaphagocytophilumt4sseffectorateaisessentialfortickinfection
AT swallowkylet ananaplasmaphagocytophilumt4sseffectorateaisessentialfortickinfection
AT nelsoncurtism ananaplasmaphagocytophilumt4sseffectorateaisessentialfortickinfection
AT oliverjonathand ananaplasmaphagocytophilumt4sseffectorateaisessentialfortickinfection
AT shawdanak ananaplasmaphagocytophilumt4sseffectorateaisessentialfortickinfection
AT munderlohulrikeg ananaplasmaphagocytophilumt4sseffectorateaisessentialfortickinfection
AT braytonkellya ananaplasmaphagocytophilumt4sseffectorateaisessentialfortickinfection
AT parkjasonm anaplasmaphagocytophilumt4sseffectorateaisessentialfortickinfection
AT generabrittanym anaplasmaphagocytophilumt4sseffectorateaisessentialfortickinfection
AT fahydeirdre anaplasmaphagocytophilumt4sseffectorateaisessentialfortickinfection
AT swallowkylet anaplasmaphagocytophilumt4sseffectorateaisessentialfortickinfection
AT nelsoncurtism anaplasmaphagocytophilumt4sseffectorateaisessentialfortickinfection
AT oliverjonathand anaplasmaphagocytophilumt4sseffectorateaisessentialfortickinfection
AT shawdanak anaplasmaphagocytophilumt4sseffectorateaisessentialfortickinfection
AT munderlohulrikeg anaplasmaphagocytophilumt4sseffectorateaisessentialfortickinfection
AT braytonkellya anaplasmaphagocytophilumt4sseffectorateaisessentialfortickinfection