title: Lower respiratory tract infection in cynomolgus macaques (Macaca fascicularis) infected with group A Streptococcus.
abstract: Group A Streptococcus (GAS), a human-specific pathogen, is best known for causing pharyngitis ("strep-throat") and necrotizing fasciitis ("flesh-eating disease"). However, the organism is also an uncommon but important cause of community-acquired bronchopneumonia, an infection with an exceptionally high mortality rate. Inasmuch as little is known about the molecular pathogenesis of GAS lower respiratory tract infection, we sought to develop a relevant human infection model. Nine cynomolgus macaques were infected by intra-bronchial instillation of either sterile saline or GAS (10(5) or 10(7) CFU). Animals were continuously monitored and sacrificed at five days post-inoculation. Serial bronchial alveolar lavage specimens and tissues collected at necropsy were used for histologic and immunohistochemical examination, quantitative microbial culture, lung and blood biomarker analysis, and in vivo GAS gene expression studies. The lower respiratory tract disease observed in cynomolgus macaques mimicked the clinical and pathological features of severe GAS bronchopneumonia in humans. This new monkey model will be useful for testing hypotheses bearing on the molecular pathogenesis of GAS in the lower respiratory tract.
authors.affiliation: Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital Research Institute, Houston, TX 77030, USA.
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Olsen
authors.forename: Madiha
authors.initials: M
authors.lastname: Ashraf
authors.forename: Vedia E
authors.initials: VE
authors.lastname: Gonulal
authors.forename: Ara A
authors.initials: AA
authors.lastname: Ayeras
authors.forename: Concepcion
authors.initials: C
authors.lastname: Cantu
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Shea
authors.forename: Ronan K
authors.initials: RK
authors.lastname: Carroll
authors.forename: Tammy
authors.initials: T
authors.lastname: Humbird
authors.forename: Jamieson L
authors.initials: JL
authors.lastname: Greaver
authors.forename: Jody L
authors.initials: JL
authors.lastname: Swain
authors.forename: Ellen
authors.initials: E
authors.lastname: Chang
authors.forename: Willie
authors.initials: W
authors.lastname: Ragasa
authors.forename: Leslie
authors.initials: L
authors.lastname: Jenkins
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Lally
authors.forename: Terry
authors.initials: T
authors.lastname: Blasdel
authors.forename: Philip
authors.initials: P
authors.lastname: Cagle
authors.forename: James M
authors.initials: JM
authors.lastname: Musser
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D001996:Bronchopneumonia / Q000382:microbiology / Q000473:pathology / Q000662:veterinary*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D008168:Lung / Q000473:pathology; D008252:Macaca fascicularis; D008297:Male; D008992:Monkey Diseases / Q000382:microbiology* / Q000473:pathology*; D013290:Streptococcal Infections / Q000382:microbiology / Q000473:pathology / Q000662:veterinary*; D013297:Streptococcus pyogenes / Q000235:genetics / Q000302:isolation & purification*
chemical_list: D015415:Biomarkers