Iron reduction in Dermacentor andersoni tick cells inhibits Anaplasma marginale replication

Authors: SOLYMAN, MUNA SALEM - Washington State University; UJCZO, JESSICA - US Department Of Agriculture (USDA); BRAYTON, KELLY - Washington State University; SHAW, DANA - Washington State University; Schneider, David; Noh, Susan

Submitted to: International Journal of Molecular Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/29/2022
Publication Date: 4/1/2022
Citation: Solyman, M.M., Ujczo, J., Brayton, K.A., Shaw, D.K., Schneider, D.A., Noh, S.M. 2022. Iron reduction in Dermacentor andersoni tick cells inhibits Anaplasma marginale replication. International Journal of Molecular Sciences. 23(7). Article 3941. https://doi.org/10.3390/ijms23073941.
DOI: https://doi.org/10.3390/ijms23073941

Interpretive Summary: The family Anaplasmataceae include bacterial pathogens that cause a number of diseases in humans and animals. These pathogens include Anaplasma marginale and A. phagocytophilum, which cause bovine and granulocytic anaplasmosis, respectively. Overall, effective measures to prevent these diseases are lacking. The fact they are transmitted by ticks presents opportunities for the development of broadly applicable interventions to prevent tick transmission. However, there are major, basic knowledge gaps in our understanding of the tick-pathogen interface limiting our ability to develop such interventions. With few exceptions, iron is an essential and limiting nutrient for bacterial pathogens and their hosts. It is a critical component of eukaryotic and prokaryotic cellular functions and is indispensable for nucleic acid synthesis, protein production, and energy generation. Thus, iron transporters are potential targets for interventions. In this study we determined that iron is required for A. marginale replication in tick cells and identify three genes that are likely involved in iron transport.

Technical Abstract: The Anaplasma spp. are obligate intracellular, tick-borne,bacterial pathogens that cause bovine and human anaplasmosis. We lack tools to prevent these diseases in part due to major knowledge gaps in our basic understanding of the tick-pathogen interface, including the requirement for and molecules involved in iron transport during tick colonization. Using Anaplasma marginale, which causes bovine anaplasmosis, and Dermacentor andersoni tick cells, we determine that iron is required for pathogen replication in tick cells. Using bioinformatics and protein modeling we identified orthologs of the Gram-Negative siderophone-independent iron uptake system, FbpABC. Am069, the A. marginale ortholog of FbpA lacks predicted iron binding residues based on the NCBI conserved domain database. However, based on protein modeling, the best structural orthologs of Am069 are iron transport proteins from Cyanobacteria and Campylobacter jejuni. We then determined that all three A. marginale genes are modestly differentially expressed in response to altered host cell iron levels, despite the lack of a fur regulator or operon structure. This work is foundational for building a mechanistic understanding of iron uptake which could lead to the development of interventions to prevent bovine and human anaplasmosis.