Anaplasma phagocytophilum outer membrane protein A interacts with sialylated glycoproteins to promote infection of mammalian host cells.

Abstract

Anaplasma phagocytophilum is the tick-transmitted obligate intracellular bacterium that causes human granulocytic anaplasmosis (HGA). A. phagocytophilum binding to sialyl Lewis x (sLe(x)) and other sialylated glycans that decorate P selectin glycoprotein 1 (PSGL-1) and other glycoproteins is critical for infection of mammalian host cells. Here, we demonstrate the importance of A. phagocytophilum outer membrane protein A (OmpA) APH_0338 in infection of mammalian host cells. OmpA is transcriptionally induced during transmission feeding of A. phagocytophilum-infected ticks on mice and is upregulated during invasion of HL-60 cells. OmpA is presented on the pathogen's surface. Sera from HGA patients and experimentally infected mice recognize recombinant OmpA. Pretreatment of A. phagocytophilum organisms with OmpA antiserum reduces their abilities to infect HL-60 cells. The OmpA N-terminal region is predicted to contain the protein's extracellular domain. Glutathione S-transferase (GST)-tagged versions of OmpA and OmpA amino acids 19 to 74 (OmpA(19-74)) but not OmpA(75-205) bind to, and competitively inhibit A. phagocytophilum infection of, host cells. Pretreatment of host cells with sialidase or trypsin reduces or nearly eliminates, respectively, GST-OmpA adhesion. Therefore, OmpA interacts with sialylated glycoproteins. This study identifies the first A. phagocytophilum adhesin-receptor pair and delineates the region of OmpA that is critical for infection.

• Authors: Nore Ojogun, Amandeep Kahlon, Stephanie A Ragland, Matthew J Troese, Juliana E Mastronunzio, Naomi J Walker, Lauren Viebrock, Rachael J Thomas, Dori L Borjesson, Erol Fikrig, Jason A Carlyon
• Journal: Infection and immunity (Infect Immun) Vol. 80 Issue 11 Pg. 3748-60 (Nov 2012) ISSN: 1098-5522 [Electronic] United States
• PMID: 22907813 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Adhesins, Bacterial
• Bacterial Outer Membrane Proteins
• Membrane Glycoproteins
• Peptidoglycan
• OMPA outer membrane proteins
• N-Acetylneuraminic Acid

Topics

• Adhesins, Bacterial
• Anaplasma phagocytophilum (genetics, metabolism)
• Animals
• Bacterial Outer Membrane Proteins (metabolism)
• CHO Cells
• Cricetinae
• Ehrlichiosis (etiology)
• HL-60 Cells
• Humans
• Membrane Glycoproteins (chemistry, metabolism)
• Mice
• Mice, Inbred C3H
• N-Acetylneuraminic Acid
• Peptidoglycan (metabolism)
• Ticks (microbiology)