Ecology of co-infection in a tick-borne pathogen

许多病原体种群由遗传上不同的菌株组成。在这些系统中，宿主经常被多种毒株感染，这种现象被称为混合感染或共感染。在混合感染中，病原体菌株可以相互作用，这些相互作用可以是合作的，也可以是竞争的。在混合感染常见的病原体群体中，研究菌株之间的相互作用如何影响它们的传播、频率和共存是至关重要的。在我之前的研究中，我使用了多株蜱传细菌，阿泽利伯氏疏螺旋体，来研究病原体菌株的种群如何在自然界中持续存在。通过长期的野外研究，我发现菌株的群落在十多年里是稳定的，而且一些菌株总是比其他菌株更常见。通过实验感染，我证明了实验室中病原体菌株之间适应性的差异解释了田间菌株之间频率的差异。这就提出了一个问题：“为什么常见和合适的菌株不能消除罕见和弱的菌株？”为了回答这个问题，我们必须研究病原体生命周期中菌株之间的相互作用。我研究的长期目标是了解多菌株病原体的种群动态。该NSERC DG包含3个目标。非传递竞争相互作用（当基因型不能按等级排列时）对生物多样性很重要，但在多菌株病原体中却被忽视了（目标1）。如果病原体具有复杂的生命周期，菌株在多种宿主类型中相互作用，那么研究这种复杂性是必要的（目标2）。最后，已知宿主免疫会影响菌株之间的竞争，但很少有人认识到，一个有能力的免疫系统可以促进共感染，特别是当一个晚到的菌株必须入侵一个已经被驻留菌株感染的宿主时（目标3）。我们将使用多株蜱传伯氏疏螺旋体的实验感染来测试啮齿动物宿主（目标1）和蜱媒介（目标2）中菌株之间的非传递性竞争相互作用是否分别影响宿主到蜱和蜱到宿主的传播，以及一个有能力的宿主免疫系统是否允许迟到的菌株感染先前感染的宿主（目标3）。这项研究将促进我们对病原体菌株之间的相互作用如何促进它们在自然种群中共存的理解。这项研究的结果将对进化生态学、微生物学和传染病生态学等领域具有重要意义。从HQP培训的角度来看，蜱传疾病是加拿大人类和动物健康日益严重的问题。由NSERC总干事培训的HQP将发展有价值的技能和知识，使他们在政府、工业和学术界的工作中具有很强的竞争力。

Many pathogen populations consist of genetically distinct strains. In these systems, the hosts are often infected with multiple strains, a phenomenon referred to as mixed infections or co-infections. In mixed infections, the pathogen strains can interact with each other and these interactions could be cooperative or competitive. In pathogen populations where mixed infections are common, it is critical to study how interactions between strains influence their transmission, frequency, and co-existence. In my previous research, I used the multi-strain tick-borne bacterium, Borrelia afzelii, to study how populations of pathogen strains persist in nature. Using a long-term field study, I showed that the community of strains was stable over a decade, and that some strains were always more common than others. Using experimental infections, I showed that variation in fitness among pathogen strains in the lab explained differences in frequencies among strains in the field. This raises the question: "Why do the common and fit strains not eliminate the rare and weak ones?" To answer this question, we must study interactions between strains across the pathogen life cycle. The long-term goal of my research is to understand the population dynamics of multi-strain pathogens. This NSERC DG contains 3 objectives. Non-transitive competitive interactions (when genotypes cannot be ranked in a hierarchy) are important for biodiversity, but have been ignored in multi-strain pathogens (Objective 1). If pathogens have complex life cycles where strains interact in multiple host types, it is essential to study this complexity (Objective 2). Finally, host immunity is known to influence competition between strains, but less appreciated is that a competent immune system can facilitate co-infection, especially when a late-arriving strain has to invade a host that is already infected with a resident strain (Objective 3). We will use experimental infections with the multi-strain tick-borne bacterium B. burgdorferi to test whether non-transitive competitive interactions between strains in the rodent host (Objective 1) and the tick vector (Objective 2) influence host-to-tick and tick-to-host transmission, respectively, and whether a competent host immune system allows a late-arriving strain to infect a previously infected host (Objective 3). This research will advance our understanding of how interactions between pathogen strains can facilitate their co-existence in natural populations. The outcomes from this research will be important to the fields of evolutionary ecology, microbiology, and the ecology of infectious diseases. From an HQP training perspective, tick-borne diseases are a growing problem for human and animal health in Canada. The HQP trained by this NSERC DG will develop valuable skills and knowledge that will make them highly competitive for jobs in government, industry, and academia.