Infection Biology and Epidemiology of Staphylococci and Staphylococcal Diseases in sub-Saharan Africa

金黄色葡萄球菌在健康和身体虚弱的人群中引起严重感染。在发达国家，金黄色葡萄球菌是一种社区或医院获得性病原体，具有广泛抗菌素耐药性的克隆现在很普遍，限制了治疗选择。然而，对病原体分布及其遗传和生物学特征的调查相对限于发达地区，而在资源稀少的热带地区，如撒哈拉以南非洲，关于病原体及其相关疾病的数据有限。从非洲分离的毒素设备上的初步迹象表明，在这些地区，不同的系统发育谱系似乎是突出的。因此，作为其目标，非洲-德国StaphNet打算通过对临床和共生起源的非洲和德国分离株进行比较分析，以及通过确定宿主反应，有助于加强对疾病机制和病程的了解。为此，在第一个资助期内，三个非洲和五个德国研究机构及其附属医院从西部、东部和南部非洲以及德国收集了临床定义明确的金黄色葡萄球菌分离株，并使用扩展的分子方法分析了这些分离株。潘通-瓦伦丁-白细胞介素在遥远的非洲土著人群中也普遍存在，除此之外，在保护区的非人类灵长类动物中也存在具有典型人类殖民者抗性特征的分离株，这是一个意想不到的新结果，具有潜在的广泛影响。在申请的新资助期内，计划对现有的1000株葡萄球菌进行更详细的调查，并提供更多的临床材料。通过结合基因表达和功能分析的现代基因组分析的应用，并在现代生物信息学分析的支持下，这些调查现在将揭示葡萄球菌基因产物的重要性以及可能与非洲葡萄球菌疾病的发病和病程有关的体液和先天免疫防御机制。该项目在很大程度上依赖于双向技术交流和能力建设的概念，使非洲和德国合作伙伴能够在具体考虑到资源有限的热带国家进行这种研究的情况下，处理葡萄球菌生物学和相关传染病的（基础）研究课题。

Staphylococcus aureus causes severe infections in healthy and compromised persons. In developed countries, S. aureus is a community or hospital acquired pathogen, and clones with broad antimicrobial resistance are nowadays widespread and limiting therapeutic options. Investigations on the distribution of the pathogen as well as on its genetic and biologic characteristics, however, are relatively limited to developed regions while in tropical areas with sparse resources such as in sub-Sahara Africa only limited data on the pathogen and its associated disease are available.First indications on the toxin equipment of isolates from Africa demonstrate that in these regions phylogenetic different lineages appear to be prominent. Accordingly, as its goal the African-German StaphNet intents by application of comparative analyses of African and German isolates both of clinical and commensal origin as well as by determination of host response to contribute to an enhanced understanding of mechanisms and course of disease. To this end, during the first funding period three African and five German research institutes and their affiliated hospitals have collected clinically well-defined S. aureus isolates from Western, Eastern, and Southern Africa as well as from Germany, and have analyzed these isolates with extended molecular methods. Apart from the demonstrated prevalence of the Panton-Valentine-Leukocidin also in isolates from remote indigenous African populations, the presence of isolates with resistance profiles typically for human colonizers even in non-human primates from sanctuaries has been a novel, unexpected result with potential wide-ranging implications. For the applied new funding period, additional detailed investigations of the now available >1000 staphylcoccal isolates and additional clinical material is planned. By application of modern genomic analyses in conjunction with gene expression and function assays, and supported by modern bioinformatic analysis, these investigations shall now reveal the importance of staphylococcal gene products and the mechanisms of humoral and innate immune defence which may be associated with onset and course of staphylococcal disease in Africa.The project heavily relies on a concept of bidirectional technology exchange and capacity building enabling both African and German partners to address (basic) research topics in staphylococcal biology and associated infectious disease under specific consideration of the conditions of such research in tropical countries with limited resources.