Lower respiratory tract infection in cynomolgus macaques (Macaca fascicularis) infected with group A streptococcus

Randall J. Olsen, Madiha Ashraf, Vedia E. Gonulal, Ara A. Ayeras, Concepcion Cantu, Patrick R. Shea, Ronan K. Carroll, Tammy Humbird, Jamieson L. Greaver, Jody L. Swain, Ellen Chang, Willie Ragasa, Leslie Jenkins, Kevin P. Lally, Terry Blasdel, Philip T. Cagle, James M. Musser

Research output: Contribution to journalArticle

10 Scopus citations

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 (105 or 107 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.

Original languageEnglish (US)
Pages (from-to)336-347
Number of pages12
JournalMicrobial Pathogenesis
Volume49
Issue number6
DOIs
StatePublished - Dec 1 2010

Keywords

  • Group A Streptococcus
  • Invasive infection
  • Lower respiratory tract
  • Non-human primate model
  • Pneumonia

ASJC Scopus subject areas

  • Microbiology
  • Infectious Diseases

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