title: Invasion of erythrocytes by Francisella tularensis.
abstract: Francisella tularensis is the causative agent of tularemia and is classified as a category A biodefense agent by the Centers for Disease Control and Prevention because of its highly infectious nature. F. tularensis infects leukocytes and exhibits an extracellular phase in the blood of the host. It is unknown, however, whether F. tularensis can infect erythrocytes; thus, we examined this possibility in vivo and in vitro. In the murine model of pulmonary type A tularemia, we showed the presence of intraerythrocytic bacteria by double-immunofluorescence microscopy and ex vivo gentamicin protection of the purified erythrocyte fraction. In vitro, F. tularensis invaded human erythrocytes, as shown in the gentamicin protection assays, double-immunofluorescence microscopy, flow cytometry, scanning electron microscopy, and transmission electron microscopy with immunogold labeling of the bacteria. Additional in vitro tests indicated that serum complement-dependent and complement-independent mechanisms contribute to erythrocyte invasion. Our results reveal a novel intraerythrocytic phase during F. tularensis infection.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, PA, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Horzempa
authors.forename: Dawn M
authors.initials: DM
authors.lastname: O'Dee
authors.forename: Donna Beer
authors.initials: DB
authors.lastname: Stolz
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Franks
authors.forename: Doris
authors.initials: D
authors.lastname: Clay
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Nau
mesh_terms: D000818:Animals; D003165:Complement System Proteins / Q000276:immunology; D004195:Disease Models, Animal; D004912:Erythrocytes / Q000382:microbiology*; D005260:Female; D005434:Flow Cytometry; D005604:Francisella tularensis / Q000254:growth & development / Q000472:pathogenicity*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D014406:Tularemia / Q000453:epidemiology / Q000382:microbiology* / Q000473:pathology*
chemical_list: D003165:Complement System Proteins