Epidemiology and ecology of Bacillus cereus biovar anthracis: A project to build capacities for the detection and investigation of novel pathogens

蜡状芽孢杆菌生物群炭疽杆菌(Bcbva)结合了环境细菌蜡样芽孢杆菌的染色体背景和炭疽杆菌的毒力质粒。这些质粒使Bcbva能够产生炭疽毒素和炭疽胶囊，导致致命感染。虽然在动物模型中的研究表明，Bcbva的毒力与BA相当，但Bcbva的形态存在差异。我们发现Bcbva广泛分布在热带非洲(从科特迪瓦(CI)到刚果民主共和国)，菌株聚集在一个独特的遗传支系中，显示出该支系内的变异性。在我们的主要研究区域塔伊国家公园(TNP)，我们证明了Bcbva至少自1989年以来已经造成了野生动物的重大死亡。在TNP中，我们发现每十分之一的腐肉苍蝇携带Bcbva。这表明，这些苍蝇可能在Bcbva的传播中发挥了作用，特别是对于树栖猴子物种。对来自TNP的&GT；150个Bcbva全基因组的分析表明，Bcbva持续爆发，几个Bcbva谱系平行存在，在哺乳动物密度较高的地区Bcbva患病率很高。通过开发一种新的Bcbva特异性试验，我们在CI中进行了血清阳性率研究，揭示了Bcbva的广泛分布，主要是在人们与野生动物接触的地区。我们还确定了CI的其他区域，人类和牲畜表现出对巴的抗体，这是由巴C分支引起的，这是美国描述的一种谱系。第二个资助期的研究将集中在决定Bcbva分布的因素(1)、Bcbva流行病学(2)和迄今未知的病原菌出现的风险(3)等关键问题上。(1)决定分布的因素将通过实地研究沿着CI的两个气候区域之间的环境梯度进行调查。这些数据将通过检测不同环境条件下Bcbva的生长和产孢量的体外研究来补充。这两种方法的综合结果将使我们能够生成Bcbva的风险图。(2)我们还将调查Bcbva的流行病学，特别是人和动物的感染途径，通过比较两个已知Bcbva发生和不同环境条件的地点的流行病学。这些数据将与实验室数据相辅相成，在实验室数据中，我们将测试Bcbva在不同介质(土壤和水果)中的生长情况，以及Bcbva与可能的媒介(腐殖蝇)的相互作用。为了确定影响人类感染风险的因素，我们将分析从已知暴露的人那里收集的调查数据。(3)最后，我们将进行实验，通过水平转移已知的毒力质粒来检测进一步出现非典型致病杆菌的可能性，以及新的潜在毒力因子的影响。这三部分将使我们能够确定Bcbva和其他非典型致病杆菌出现的风险因素，并制定当地对策。

Bacillus cereus biovar anthracis (Bcbva) combines the chromosomal background of B. cereus, an environmental bacterium, with the virulence plasmids of B. anthracis (Ba). These plasmids enable Bcbva to produce anthrax toxins and the anthrax capsule, causing lethal infection. While studies in animal models suggest that the virulence of Bcbva is comparable to that of Ba, morphological differences of Bcbva were detected. We showed that Bcbva is widespread in tropical Africa (from Cote d Ivoire (CI) to the Democratic Republic of Congo), with strains clustering in one unique genetic clade, displaying variability within the clade. In our main study area Taï National Park (TNP), CI, we demonstrated that Bcbva has caused major die-offs in wildlife since at least 1989. In TNP we found that every tenth carrion fly carries Bcbva. This suggests that these flies may play a role in Bcbva transmission, particularly for arboreal monkey species. An analysis of > 150 full Bcbva genomes from TNP points towards a continuous outbreak with several Bcbva lineages present in parallel and high Bcbva prevalence in areas with high mammal density. By developing a novel Bcbva specific assay we conducted seroprevalence studies in CI, revealing a wide distribution of Bcbva, mainly in areas where people live in contact to wildlife. We also identified other regions of CI where humans and livestock exhibit antibodies against Ba, caused by the Ba C branch, a lineage described in the United States. Research in the second funding period will focus on key questions regarding factors determining Bcbva distribution (1), Bcbva epidemiology (2) and the risk of emergence of so far unknown pathogenic bacilli (3). (1) Factors determining distribution will be investigated in field studies along an environmental gradient between two climatic regions in CI. These data will be complemented by in vitro studies examining growth and sporulation of Bcbva under varying environmental conditions. Combined results from both approaches will allow us to generate a risk map for Bcbva. (2) We will also investigate Bcbva epidemiology; specifically routes for infection in humans and animals, by comparing the epidemiology at two sites with known Bcbva occurrence and different environmental conditions. These data will be complemented with laboratory data, where we will test for Bcbva growth in different media (soil and fruits) and the interaction of Bcbva with possible vectors (carrion flies). To determine factors influencing human infection risk, we will analyze survey data collected from people with known exposition. (3) Lastly, we will perform experiments to examine the potential emergence of further atypical pathogenic bacilli by horizontal gene transfer of known virulence plasmids and the influence of new potential virulence factors. These three parts will allow us to determine risk factors for the emergence of Bcbva and other atypical pathogenic bacilli and to develop local countermeasures.