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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本研究的目的是建立一种非人灵长类动物的莫拉氏菌属细菌引起的持续性感染和疾病模型。广泛的，长期的目标是利用这样的模型在研究的发病机制和免疫预防疾病引起的卡他莫拉菌。这种细菌正在成为呼吸道和中耳疾病的主要病原体，但没有足够的动物模型来研究疾病的发病机制或免疫预防。我们的第一个目标是确定人类分离的M。卡他炎至少可以在恒河猴的鼻咽（NP）定植，最好的情况是引起鼻出血和/或中耳炎OM。2只动物鼻咽接种人菌株KSA，6只动物接种人菌株7169。只有一只动物（给予M。卡他菌菌株7169）持续可检测的定殖2周。该动物还出现鼻衄。看来，M。卡他病主要是人类宿主特异性的。我们现在计划对上述4只动物接种恒河猴莫拉氏菌分离株CI 24。我们将连续监测这些动物的定植、鼻衄和OM。预期接种这些最初从患有鼻出血的恒河猴分离的细菌将通过定殖NP并在大多数动物中引起鼻出血来实现Koch假设。我们还将监测OM的发生率。如果恒河猴莫拉氏菌除了引起鼻出血外还引起OM，OM是这种感染的一个方面，迄今尚未研究，那么这种细菌，不是M。粘膜炎，将成为一种在群体恒河猴中具有重要兽医意义的病原体。下一步将是评估恒河猴莫拉氏菌不仅作为人类病原体的模型，而且作为兽医用疫苗的靶点。

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.