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

Abstract

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 colonization are mostly unknown, and a human-relevant animal model is needed. Here, we screened 17 pig-tailed macaques () for 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, 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 colonization was established with 10 CFU/nostril, and both autologous and nonautologous strains survived over 40 days without any apparent adverse effects. A human nasal isolate (strain D579, sequence type 398) was carried in 4 of 6 animals for over 3 weeks. Nostrils that did eradicate experimentally applied 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 nasal carriage that may be utilized for testing natural colonization and decolonization mechanisms as well as novel classes of anti- therapeutics.

Antigen-Presenting Cells in the Airways: Moderating Asymptomatic Bacterial Carriage

“…Additionally, nasal S. aureus persistence correlated with high baseline levels of MIP-1β, IL-6, and IL-1β, combined with an absence of upregulation of pro-inflammatory cytokines upon inoculation. These findings were confirmed in a similar macaque model for asymptomatic S. aureus carriage [ 75 ]. The effect of pre-existing differences in host immune environment at the time of pathogen acquisition fits with the clinical observation that pre-existing inflammation can predispose the host for carriage or infection with a secondary pathogen.…”

Efficient infection of non-human primates with purified, cryopreserved Plasmodium knowlesi sporozoites

“…However, due to COVID-19 research, the US is currently facing a shortage of rhesus macaques, suggesting that identification of a suitable alternative macaque species for malaria vaccine studies may be useful. Pigtailed macaques are closely related to rhesus macaques, and are used as models to study numerous infectious diseases, including HIV [ 47 , 48 ], chlamydia [ 49 ], Zika [ 50 ] and Staphylococcus aureus [ 51 ]. Pig-tailed macaques are notably also the natural forest host of P. knowlesi malaria parasites [ 52 ].…”

Identification of Nasal Gammaproteobacteria with Potent Activity against Staphylococcus aureus: Novel Insights into the “Noncarrier” State

“…We demonstrated that nasal fluids of human S. aureus carriers have less intrinsic anti- S. aureus activity than nasal fluids collected from noncarriers ( 15 , 24 , 25 ) even though the basal components of nasal secretions (e.g., amino acids, salts, organic acids, trace elements, sugars) are not variable between donors ( 26 ). Host antimicrobial peptide polymorphisms fail to distinguish S. aureus carriers from noncarriers, and HNP1 to -3 and various cytokine levels are elevated in carriers, suggesting that these proteins are more the result of SANC than a reason for noncarrier status ( 13 , 15 , 21 , 27 ). Collectively, these insights led us to the current question of how the constantly fluctuating nasal microbiota affect SANC status.…”