Type IV secretion system of Anaplasma phagocytophilum and Ehrlichia chaffeensis.

The intracellular bacterial pathogens Ehrlichia chaffeensis and Anaplasma phagocytophilum have evolved to infect leukocytes and hijack biological compounds and processes of these host defensive cells. Bacterial type IV secretion (T4S) system transports macromolecules across the membrane in an ATP-dependent manner and is increasingly recognized as a virulence factor delivery mechanism that allows pathogens to modulate eukaryotic cell functions for their own benefit. Genes encoding T4S system homologous to those of a plant pathogen Agrobacterium tumefaciens have been identified in E. chaffeensis and A. phagocytophilum. Upon interaction with new host cells, E. chaffeensis and A. phagocytophilum genes encoding the T4S apparatus are upregulated. The delivered macromolecules are referred to as T4S substrates, or effectors, because they affect and alter basic host cellular processes, resulting in disease development. Recently, A. phagocytophilum 160-kDa AnkA protein was to be delivered by T4S system into the host cytoplasm. Thus, dynamic signal transduction events are likely induced by T4S substrates in the host cells for successful establishment of intracellular infection. Further studies on Ehrlichia and Anaplasma T4S effectors cognate host cell molecules will undoubtedly advance our understanding of the complex interplay between obligatory intracellular pathogens and their hosts. Such data can be applied toward treatment, diagnosis, and control of ehrlichiosis and anaplasmosis.