Determinants for the spread of Panton-Valentine leukocidin positive Staphylococcus aureus in Africa

金黄色葡萄球菌是一种世界范围内的细菌病原体，可引起各种感染（例如皮肤感染、肺炎、心脏瓣膜感染）。S.金黄色葡萄球菌形成多种毒素（毒力因子），其影响金黄色葡萄球菌的病程。金黄色葡萄球菌感染一种毒素是Panton-Valentine杀白细胞素（PVL），它可能与严重的皮肤和软组织感染有关。这种毒素在欧洲分离株中非常罕见（1-2%）。然而，在非洲分离株中，它更为常见（约50%）。由于该毒素很可能具有很大的临床意义，我们将在本提案中研究PVL阳性S.金黄色葡萄球菌在非洲初步研究表明，这种传播的可能因素很可能与人类宿主有关，而与病原体本身或环境无关。目的：寻找宿主中有利于PVL阳性S. aureus，我们想比较非洲和德国的参与者。为此，我们将从非洲和德国志愿者中采集血液样本，以研究宿主与PVL在三个水平上的相互作用。我们希望研究（i）PVL与血清蛋白的相互作用，（ii）PVL与白细胞上的结合受体的相互作用，以及（iii）PVL在细胞表面结合后在细胞内的反应。拟议研究的关键点是在非洲创造资源并不断培训我们的非洲合作伙伴。该项目涉及德国的两个研究中心（明斯特、耶拿）和非洲的三个研究实验室（刚果共和国的布拉柴维尔、尼日利亚的Ile-Ife、加蓬的Lambaréné）。通过比较非洲人和德国人，我们希望找到解释PVL阳性S.金黄色葡萄球菌在非洲分离。只有了解非洲PVL阳性分离株传播的因素，才能制定适当的感染控制措施。

Staphylococcus aureus is a worldwide bacterial pathogen, which can cause various infections (e.g. skin infections, pneumonia, heart valves infections). S. aureus forms a variety of toxins (virulence factors) which influence the course of S. aureus infections. One toxin is the Panton-Valentine leukocidin (PVL), which can be associated with severe skin and soft tissue infections. This toxin is very rare in European isolates (1-2%). In African isolates, however, it is much more common (about 50%). Since the toxin very likely has a great clinical significance, we will examine in this proposal possible reasons for the spread of PVL-positive S. aureus in Africa. Preliminary work has shown that possible factors for this dissemination are most likely associated with the human host and not with the pathogen itself or the environment. To find possible factors of the host that favor the spread of PVL-positive S. aureus, we want to compare African and German participants. For this purpose, we will take blood samples from African and German volunteers in order to investigate the interaction of the host with PVL at three levels. We want to examine (i) the interaction of PVL with serum proteins, (ii) the interaction of PVL with its binding receptor on leukocytes, and (iii) the reaction inside the cell after binding of PVL at the cell surface.A key point of the proposed research is the creation of resources in Africa and the continuous training of our African partners. This is the basis for a sustainable development perspective for future collaborations.The project involves two research sites in Germany (Münster, Jena) and three research laboratories in Africa (Brazzaville in the Republic of Congo, Ile-Ife in Nigeria, Lambaréné in Gabon).By comparing Africans and Germans, we hope to find the factors that explain the high prevalence of PVL-positive S. aureus isolates in Africa. Only when the factors for the spread of PVL-positive isolates in Africa are known, one could develop appropriate infection control measures.