Porphyromonas pigment in bovine footrot: implications in pathophysiology and treatment

厌氧细菌在缺氧条件下生长。虽然人们发现厌氧菌在许多情况下越来越多地导致疾病，但对厌氧菌的研究严重不足，部分原因是处理这些生物很困难。我的实验室一直在研究这些感染，我们采用由卟啉单胞菌引起的牛足病（BFR）作为模型系统，卟啉单胞菌是一种黑色厌氧菌，协同作用导致了这种疾病。BFR作为厌氧感染的完美模型系统，被加拿大农民认为是值得注意的，是传统动物生产中的重大刺激，也是动物不适和跛行的主要原因。随着动物福利问题的加剧，以及目前抗生素的使用受到更严格的审查，像BFR这样的传染病将产生更大的影响。随着社会上限制大规模抗生素使用（目前的控制方法）的压力增加，更充分地了解BFR至关重要。由于其复杂的多微生物性质，在世界各地的牛中普遍存在，急性化脓性特征(即。脓液形成是受感染动物的BFR反应的典型特征，它作为细菌协同作用模型的适用性，从而为其他此类感染提供了见解。关键是白细胞的性质和功能，如中性粒细胞（PMN）和巨噬细胞，在解决或缺乏解决，BFR(即。死亡/垂死的PMN是脓液的主要成分)。毫无疑问，BFR的严重程度取决于细菌的复杂相互作用，包括它们的毒力特性（如黑色色素）和牛宿主，包括动物的免疫细胞反应（PMN和巨噬细胞）。我的实验室专门研究这些现象。一段时间以来，我们一直在单独评价李氏弧菌的毒力。多年来，我们一直在研究牛PMN和巨噬细胞，并结合我们在抗菌素耐药性研究方面的兴趣和能力。本研究计划通过细菌色素在感染、病理生理和治疗抗性中发挥的独特作用，将这些兴趣结合起来。

Anaerobic bacteria grow in the absence of oxygen. While they are being found to increasingly contribute to disease in many settings the study of anaerobes is grossly under-represented due in part to the difficulty in working with these organisms. My lab has been involved in studying these infections and we employ as a model sytem bovine footrot (BFR) caused by Porphyromonas levii, a black-pigmented anaerobe that synergistically contributes to the disease. BFR serves as a perfect model system for anaerobic infection and is perceived by Canadian farmers as noteworthy, a significant irritation in conventional animal production, as well as a major cause of animal discomfort and lameness. As animal welfare concerns intensify, and as current uses of antibiotics are scrutinized more closely, infectious diseases such as BFR will have much larger impact. Understanding BFR more fully is critical as the pressures to restrict large-scale antibiotic use (current control method) increase in society. BFR infection is intellectually intriguing because of its complex polymicrobial nature, its ubiquity in the world's cattle, the acute pyogenic character (ie. pus formation typifies BFR) of the response in affected animals, and its suitability as a model of bacterial synergism, hence providing insight in other such infections. Critical are the nature and function of white blood cells such as neutrophilic leukocytes (PMN) and macrophages in resolution, or lack of resolution, of BFR (ie. dead/dying PMN are the primary constituent of pus). The severity of BFR unquestionably hinges on a complex interplay of the bacteria including their repertoire of virulence attributes (such as the black pigment) and the cattle host, including the animals' immune cell responses (PMN and macrophages). My lab specializes in examining these phenomena. For some time now we have been alone in evaluation of the virulence of P.levii. We have studied bovine PMN and macrophages, in conjunction with our interests and capability in the antimicrobial resistance research, for years. This research proposal coalesces these interests through the unique role bacterial pigment plays in infection, pathophysiology, and resistance to treatment.