Anaplasma phagocytophilum surface protein AipA mediates invasion of mammalian host cells. (3rd April 2014)

• Record Type: Journal Article
• Authors: Seidman, David; Ojogun, Nore; Walker, Naomi J.; Mastronunzio, Juliana; Kahlon, Amandeep; Hebert, Kathryn S.; Karandashova, Sophia; Miller, Daniel P.; Tegels, Brittney K.; Marconi, Richard T.; Fikrig, Erol; Borjesson, Dori L.; Carlyon, Jason A.
• Is Part Of: Cellular microbiology. Volume 16:Number 8(2014:Aug.)
• Page Start: 1133
• Page End: 1145
• Publication Date: 2014-04-03
• Subjects: Microbiology -- Periodicals; Cytology -- Periodicals; Host-parasite relationships -- Periodicals; Microbiology -- Periodicals; Cells -- Periodicals; Microbiologie -- Périodiques; Microbiologie; Relation hôte-parasite; Cytologie; Cellule; Réponse cellulaire; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); 579.05
• DOI: 10.1111/cmi.12286
• Languages: English
• ISSNs: 1462-5814

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p> <italic>A</italic> <italic>naplasma phagocytophilum</italic>, which causes granulocytic anaplasmosis in humans and animals, is a tick‐transmitted obligate intracellular bacterium that mediates its own uptake into neutrophils and non‐phagocytic cells. Invasins of obligate intracellular pathogens are attractive targets for protecting against or curing infection because blocking the internalization step prevents survival of these organisms. The complement of <italic>A</italic><italic>. phagocytophilum</italic> invasins is incompletely defined. Here, we report the significance of a novel <italic>A</italic><italic>. phagocytophilum</italic> invasion protein, AipA. <italic>A</italic><italic>. phagocytophilum</italic> induced <italic>aipA</italic> expression during transmission feeding of infected ticks on mice. The bacterium upregulated <italic>aipA</italic> transcription when it transitioned from its non‐infectious reticulate cell morphotype to its infectious dense‐cored morphotype during infection of HL‐60 cells. AipA localized to the bacterial surface and was expressed during <italic>in vivo</italic> infection. Of the AipA regions predicted to be surface‐exposed, only residues 1 to 87 (AipA<sub>1–87</sub>) were found to be essential for host cell invasion. Recombinant AipA<sub>1–87</sub> protein bound to and competitively inhibited <italic>A</italic><italic>. phagocytophilum</italic> infection of mammalian cells. Antiserum specific for AipA<sub>1–87</sub>, but not other AipA regions, antagonized infection. Additional blocking experiments using peptide‐specific antisera narrowed down the AipA invasion domain to residues 9 to 21. An antisera combination targeting AipA<sub>1–87</sub> together with two other <italic>A</italic><italic>. phagocytophilum</italic> invasins, OmpA and Asp14, nearly abolished infection of host cells. This study identifies AipA as an <italic>A</italic><italic>. phagocytophilum</italic> surface protein that is critical for infection, demarcates its invasion domain, and establishes a rationale for targeting multiple invasins to protect against granulocytic anaplasmosis.</p> </abstract>