Evaluation of the Pig-Tailed Macaque (Macaca nemestrina) as a Model of Human Staphylococcus aureus Nasal Carriage

Abstract

<i>Staphylococcus aureus</i> nasal carriage is a common condition affecting both healthy and immunocompromised populations and provides a reservoir for dissemination of potentially infectious strains by casual contact. The factors regulating the onset and duration of nasal <i>S. aureus</i> colonization are mostly unknown, and a human-relevant animal model is needed. Here, we screened 17 pig-tailed macaques (<i>Macaca nemestrina</i>) for <i>S. aureus</i> carriage, and 14 of 17 animals tested positive in the nose at one or both screening sessions (8 weeks apart), while the other 3 animals were negative in the nose but positive in the pharynx at least once. As in humans, <i>S. aureus</i> colonization was densest in the nose, and treatment of the nostrils with mupirocin ointment effectively cleared the nostrils and 6 extranasal body sites. Experimental nasal <i>S. aureus</i> colonization was established with 10⁴ CFU/nostril, and both autologous and nonautologous strains survived over 40 days without any apparent adverse effects. A human nasal <i>S. aureus</i> isolate (strain D579, sequence type 398) was carried in 4 of 6 animals for over 3 weeks. Nostrils that did eradicate experimentally applied <i>S. aureus</i> exhibited neutrophilic innate immunity marked by elevated nasal interleukin-1β (IL-1β), IL-8, and monocyte chemotactic protein 1 levels and a 10-fold decreased IL-1 receptor antagonist/IL-1β ratio within 7 days postinoculation, analogous to the human condition. Taken together, pig-tailed macaques represent a physiological model of human <i>S. aureus</i> nasal carriage that may be utilized for testing natural colonization and decolonization mechanisms as well as novel classes of anti-<i>S. aureus</i> therapeutics.