Direct targeting of the WAVE-regulatory complex and the actin cytoskeleton by the Anaplasma phagocytophilum effector, AnkA
- 1Bristol Veterinary School, University of Bristol, Bristol, UK
Abstract
The obligate intracellular tick-borne pathogen Anaplasma phagocytophilum is unusual in its tropism for neutrophils, within which it survives and replicates. Central to the ability of this bacterium to colonize this hostile niche are secreted effector proteins. One such effector protein, AnkA, interacts with multiple host ligands in both the cytoplasm and the nucleus, yet how these interactions promote infection is largely unknown. We discovered that AnkA directly binds both the WAVE Regulatory Complex (WRC), a signal-integration hub that regulates the formation of branched actin networks underpinning diverse cell functions, and to monomeric and filamentous actin. We determined that AnkA uses two forms of molecular mimicry, first by binding to the Abi1 component of the WRC via a WRC-Recruiting Abi-binding Peptide (WRAP), and second by binding to actin via a WH2-like Actin Binding Motif (ABM). Via these interactions, AnkA can exert multi-factorial influence on the actin cytoskeleton and signaling pathways converging on this host structure. AnkA and the WRC co-localise during bacterial internalization and during the late stages of infection, suggesting a central role in both host-cell colonization and bacterial dissemination. Our work reveals AnkA as the first example of a bacterial effector that directly targets the WRC. The co-occurrence of WRAP- and ABM-like motifs in other bacterial effector proteins suggests that this mechanism of actin cytoskeleton subversion may represent a conserved strategy used by other obligate intracellular bacteria.
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BibTeX
@misc{burge2026direct,
title = {{Direct targeting of the WAVE-regulatory complex and the actin cytoskeleton by the Anaplasma phagocytophilum effector, AnkA}},
author = {H. L. Burge and S. P. Singh and J. Wang and S. Pradhan and K. M. Wood and J. W. Lee and R. Barringer and S. A. Synowsky and S. L. Shirran and P. J. Moynihan and A. L. Lovering and L. M. Machesky and M. A. Jepson and S. J. Dumler and I. T. Cadby},
howpublished = {bioRxiv},
year = {2026},
month = jul,
doi = {10.64898/2026.07.31.742066},
url = {https://www.biorxiv.org/content/10.64898/2026.07.31.742066v2},
note = {CC BY},
}
RIS
TY - UNPB
TI - Direct targeting of the WAVE-regulatory complex and the actin cytoskeleton by the Anaplasma phagocytophilum effector, AnkA
AU - H. L. Burge
AU - S. P. Singh
AU - J. Wang
AU - S. Pradhan
AU - K. M. Wood
AU - J. W. Lee
AU - R. Barringer
AU - S. A. Synowsky
AU - S. L. Shirran
AU - P. J. Moynihan
AU - A. L. Lovering
AU - L. M. Machesky
AU - M. A. Jepson
AU - S. J. Dumler
AU - I. T. Cadby
PY - 2026
DA - 2026/07/31
PB - bioRxiv
DO - 10.64898/2026.07.31.742066
UR - https://www.biorxiv.org/content/10.64898/2026.07.31.742066v2
AB - The obligate intracellular tick-borne pathogen Anaplasma phagocytophilum is unusual in its tropism for neutrophils, within which it survives and replicates. Central to the ability of this bacterium to colonize this hostile niche are secreted effector proteins. One such effector protein, AnkA, interacts with multiple host ligands in both the cytoplasm and the nucleus, yet how these interactions promote infection is largely unknown. We discovered that AnkA directly binds both the WAVE Regulatory Complex (WRC), a signal-integration hub that regulates the formation of branched actin networks underpinning diverse cell functions, and to monomeric and filamentous actin. We determined that AnkA uses two forms of molecular mimicry, first by binding to the Abi1 component of the WRC via a WRC-Recruiting Abi-binding Peptide (WRAP), and second by binding to actin via a WH2-like Actin Binding Motif (ABM). Via these interactions, AnkA can exert multi-factorial influence on the actin cytoskeleton and signaling pathways converging on this host structure. AnkA and the WRC co-localise during bacterial internalization and during the late stages of infection, suggesting a central role in both host-cell colonization and bacterial dissemination. Our work reveals AnkA as the first example of a bacterial effector that directly targets the WRC. The co-occurrence of WRAP- and ABM-like motifs in other bacterial effector proteins suggests that this mechanism of actin cytoskeleton subversion may represent a conserved strategy used by other obligate intracellular bacteria.
ER -