Variation in fitness and infection phenotype among strains of Borrelia burgdorferi emerging in Canada
Date
2023-08-17
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
ORCID
0000-0002-9418-3009
Type
Thesis
Degree Level
Doctoral
Abstract
Evolutionary virulence theory is life history theory for pathogens that explains why pathogen-induced damage (virulence) to the host is adaptive. Virulence theory examines the relationships between three pathogen life history traits: within-host replication and pathogen abundance in host tissues, pathogen transmission, and the damage caused to the host by the pathogen (virulence). Pathogen abundance in host tissues is positively correlated with pathogen transmission to new hosts. Higher pathogen abundance in host tissues also leads to higher levels of host exploitation, which should increase the pathogen-induced mortality rate or virulence. Thus, there is a positive relationship between virulence and transmission, which represents a life history trade-off for the pathogen. By increasing its exploitation of the host, the pathogen obtains the benefit of more current transmission at the cost of a shorter duration of infection. If the relationship between virulence and transmission is one of diminishing returns, natural selection should favour the evolution of an an optimal value of virulence to maximize lifetime transmission. In summary, virulence theory allows us to understand the selective pressures influencing the evolution of pathogen life history traits.
Borrelia burgdorferi is a tick-borne spirochete bacterium that causes Lyme borreliosis, the most common tick-borne disease in the Northern Hemisphere. In North America, B. burgdorferi is commonly vectored by the black-legged tick Ixodes scapularis, which acquires the infection from competent reservoir hosts. Borrelia burgdorferi is comprised of genetically distinct strains. These strains coexist in the same tick and vertebrate host populations at different frequencies and are variable in their life history traits.
For this study, we investigated the relationships between the three canonical pathogen life history traits of pathogen abundance in host tissues, transmission, and virulence among 11 strains of B. burgdorferi. Mice (male and female Mus musculus C3H/HeJ) were experimentally infected by tick bite with 1 of the 11 strains. To measure lifetime host-to-tick transmission, mice were infested with I. scapularis larval ticks at days 30, 60, and 90 post-infection (PI). To track the spirochete population in the host over time, the spirochete load was estimated in ear biopsies at days 29, 59, and 89 PI using qPCR. The mouse serum IgG antibody response against B. burgdorferi was measured at days 28 and 97 PI. Mice were euthanized at day 97 PI and necropsy tissues (left ear, right ear, ventral skin, tibiotarsal joint, heart, bladder, and kidney) were tested for their spirochete loads by qPCR. Over the course of the infection, weight gain and ankle swelling were measured as possible virulence phenotypes. Mouse necropsy tissues (kidney, ventral skin, tibiotarsal joint, and heart) were also prepared for histopathology.
As expected, we found significant variation among the 11 B. burgdorferi strains in each of the three life history traits. As predicted by evolutionary virulence theory, we found a significant positive relationship between spirochete load in the mouse tissues and lifetime host-to-tick transmission. Our lab-based estimates of mouse tissue spirochete load and lifetime host-to-tick transmission were also significantly positively related to the frequencies of these strains in natural populations of I. scapularis ticks. Our study suggests a simple mechanism where strains that reach a greater abundance in the tissues of their host have greater transmission to feeding ticks and are therefore more common in nature. We did not find a relationship between virulence and the other pathogen life history traits. Instead, we found that the host immune response was positively related to our ankle swelling measure of virulence.
Finally, this experimental infection study used both male and female C3H/HeJ mice. To the best of our knowledge, we report here the first finding of a sex-specific difference in the abundance of B. burgdorferi in the tissues of a rodent host. This sex-specific difference was also found for transmission, where ticks that fed on male mice were more likely to be infected than ticks that fed on female mice. Females had a significantly stronger antibody response to B. burgdorferi, which is consistent with known sex-specific differences in immune responses. Interestingly, female mice had higher levels of carditis compared to male mice suggesting that the immune response rather than heart spirochete loads were responsible for this sex-specific difference in pathology.
Description
Keywords
Borrelia burgdorferi, Borrelia, pathogen evolution, virulence, vector-borne, Lyme
Citation
Degree
Doctor of Philosophy (Ph.D.)
Department
Veterinary Microbiology
Program
Veterinary Microbiology