title: Ixodes scapularis salivary gland protein P11 facilitates migration of Anaplasma phagocytophilum from the tick gut to salivary glands.
abstract: Ixodes ticks harbour several human pathogens belonging to the order Rickettsiales, including Anaplasma phagocytophilum, the agent of human anaplasmosis. When ticks feed on A. phagocytophilum-infected mice, the pathogen enters the ticks' gut. The bacteria then migrate from the gut to infect the salivary glands of the ticks and are transmitted to the next host via the saliva. The molecular mechanisms that enable the migration of A. phagocytophilum from the gut to the salivary glands are poorly understood. Here we show that a secreted tick protein, P11, is important in this process. We show that P11 enables A. phagocytophilum to infect tick haemocytes, which are required for the migration of A. phagocytophilum from the gut to the salivary glands. Silencing of p11 impaired the A. phagocytophilum infection of tick haemocytes in vivo and consequently decreased pathogen infection of the salivary glands. In vitro experiments showed that P11 could bind to A. phagocytophilum and thus facilitate its infection of tick cells. This report provides new insights into A. phagocytophilum infection of ticks and reveals new avenues to interrupt the life cycle of Anaplasma and related Rickettsial pathogens.
authors.affiliation: Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, 300 Cedar Street, PO Box 208022, New Haven, Connecticut 06520-8022, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Sukanya
authors.initials: S
authors.lastname: Narasimhan
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Dai
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
authors.forename: Gong
authors.initials: G
authors.lastname: Cheng
authors.forename: Erol
authors.initials: E
authors.lastname: Fikrig
mesh_terms: D041081:Anaplasma phagocytophilum / Q000502:physiology*; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D016873:Ehrlichiosis / Q000382:microbiology; D005247:Feeding Behavior / Q000502:physiology; D041981:Gastrointestinal Tract / Q000382:microbiology*; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006434:Hemocytes / Q000382:microbiology; D006458:Hemolymph / Q000382:microbiology; D006801:Humans; D018884:Ixodes / Q000276:immunology*; D051379:Mice; D009068:Movement; D010587:Phagocytosis; D011485:Protein Binding; D015800:Protozoan Proteins / Q000276:immunology / Q000378:metabolism*; D012469:Salivary Glands / Q000382:microbiology*; D012471:Salivary Proteins and Peptides / Q000235:genetics / Q000378:metabolism*
chemical_list: D000913:Antibodies, Protozoan; D015800:Protozoan Proteins; D012471:Salivary Proteins and Peptides