A RHESUS MODEL FOR COLONIZATION AND DISEASE WITH BACTERIA OF THE GENUS MORAXELLA

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this proposal is to establish a nonhuman primate model of persistent infection and disease caused by bacteria of the genus Moraxella. The broad, long-term objective is to utilize such a model in the study of pathogenesis and immunoprophylaxis of disease caused by Moraxella catarrhalis. This bacterium is emerging as a major etiologic agent of diseases of the respiratory tract and middle ear but there are no animal models of Moraxella infection that are adequate to study disease pathogenesis or immunoprophylaxis. Our first goal was to determine whether a human isolate of M. catarrhalis could, at the very least, colonize the nasopharynx (NP) of rhesus macaques and, at best, elicit epistaxis and/or otitis media OM. Two animals were given a nasopharyngeal inoculation with human strain KSA, and 6 animals with the human strain 7169. Only one of the animals (given M. catarrhalis strain 7169) sustained detectable colonization for 2 weeks. This animal also exhibited epistaxis. It appears, therefore, that M. catarrhalis is largely human-host specific. We now plan to give 4 of the above animals an inoculation with rhesus Moraxella isolate CI24. We would monitor these animals serially for colonization, epistaxis, and OM. The expectation is that inoculation with these bacteria, which were originally isolated from a rhesus macaque with epistaxis, will fulfill Koch's postulates by colonizing the NP of, and causing epistaxis in the majority of the animals. We will also monitor the incidence of OM. If the rhesus Moraxella causes OM in addition to epistaxis, OM being an aspect of this infection hitherto not explored, then this bacterium, which is not M. catarrhalis, would emerge as a pathogen of significant veterinary importance in colony rhesus. The next step would be to evaluate rhesus Moraxella not only as model for the human pathogen but also as a target for a vaccine for veterinary use.