Collaborative Research: Tradeoffs between specialist and generalist strategies for host immune evasion in a vector-borne bacterium

This research addresses a unique example of how the environment can impact human and animal health by shaping bacterial communities in nature. Microbes causing human or animal disease differ in the number of hosts they can infect; while some specialize on a single animal/plant, others are able to infect a wide range. Specialist organisms may be better able to escape the host immune system and thus survive, but they risk becoming extinct if the host becomes rare. Pathogens with wide host ranges are often better able to 'jump' to new hosts, driving epidemics. This award will investigate how Borrelia burgdorferi - the bacterium that causes Lyme disease - escapes killing by the immune system of its natural host and whether different genetic types of this bacterium are uniquely adapted to mammals versus birds in nature. This award will also investigate whether Borrelia diversity is explained by adaptation to different hosts or, alternatively, by the targeting of the most common strains by host antibodies, allowing coexistence of rarer strains. Borrelia diversity directly impacts human health because strains cause differential disease severity. This award will increase knowledge about how ecology and evolution of microbes impacts human health. It will develop educational materials and expand outreach into communities about the links between the environment and human health. In addition, it will provide extensive and interdisciplinary training, at all educational levels, in the fields of disease ecology, molecular ecology and eco-epidemiology.<br/><br/>This award will determine the extent of specialization and immune-mediated competition among strains of B. burgdorferi in different ecological contexts and test the hypothesis that these phenotypic traits are important drivers of B. burgdorferi diversity, community structure and host specialization evolution. While there is evidence of differential B. burgdorferi host association which could drive genetic polymorphisms ('multiple niche polymorphism'), other studies claim that immune-mediated balancing selection acting on one or more B. burgdorferi outer surface proteins can maintain the observed polymorphisms without invoking directional processes ('negative frequency-dependent selection'). This award will disentangle the contribution of multiple mechanisms to B. burgdorferi diversity by assessing strain prevalence in multiple host species by applying deep amplicon sequencing to data from a 6-year-long study in a simplified host community. The physiological basis of host specificity will be explored by evaluating in vitro survival of B. burgdorferi strains when exposed to immune components in serum of different local hosts. Host-specificity related fitness and immune-mediated competition between strains will be assessed with in vivo transmission experiments. The processes by which host specialization and immune-mediated competition determine strain diversity and evolution in different ecological contexts will be examined using novel mathematical models. This study will provide strong evidence of the nature of B. burgdorferi adaptations to avoid the immune system of its natural hosts. It will determine whether these adaptations are species-specific and identify the consequences of host specificity on the structure and diversity of B. burgdorferi strain community. The award will provide multi-disciplinary training to graduate students, including under-represented minorities, and postdoctoral fellows in disease ecology and modeling. To broaden the impact of the work, researchers will leverage contacts with local environmental groups to conduct outreach within the local community.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.