How Genetic Variants Shape a Tick-Borne Disease
Imagine a pathogen so adaptable that it can circulate between ticks, rodents, and humans, constantly reshaping its identity to survive in these completely different environments.
This isn't science fiction—it's the reality of Borrelia afzelii, one of the primary bacteria behind Lyme borreliosis in Europe and Asia. While many people have heard of Lyme disease, few realize that the bacterium responsible is actually a master of genetic transformation, with different genetic variants exhibiting unique properties that influence everything from which animals they infect to how they respond to our treatments.
Core genome divergence between B. afzelii and B. garinii 6
Recent scientific breakthroughs have begun to unravel the genetic secrets of this elusive pathogen. Through advanced genomic sequencing and ecological studies, researchers are discovering how Borrelia afzelii's genetic diversity enables it to persist in nature, evade our immune systems, and in some cases, resist antibiotic treatment.
When researchers talk about Borrelia afzelii, they're not referring to a single identical bacterium but to a collection of genetic variants that share a common family lineage yet differ in important ways. These variants arise through genetic mutations and reorganizations that occur as the bacteria adapt to different host species and environmental conditions.
Borrelia afzelii belongs to what scientists call the Borrelia burgdorferi sensu lato complex—a group of genetically related bacteria that cause Lyme disease worldwide 7 . Within this complex, different genospecies have evolved to specialize in infecting particular types of hosts.
Borrelia afzelii shows a strong preference for rodents and small mammals, while its close relative Borrelia garinii specializes in bird hosts 5 . This specialization isn't arbitrary—it's driven by genetic differences that enable each variant to better survive in specific host environments.
The genetic variation among Borrelia afzelii strains isn't just academic trivia—it has real-world consequences for human health. Different genetic variants may:
A recent study in Germany's Swabian Alb region demonstrated how ecological factors shape this genetic diversity. Researchers found that areas with higher large mammal diversity supported greater diversity of Borrelia genospecies 1 5 . This happens because each host species exerts unique evolutionary pressures on the bacteria, essentially guiding the development of new genetic variants specialized for that particular host.
Ecological diversity drives genetic diversity in Borrelia populations, with implications for disease transmission and severity 1 .
| Genospecies | Primary Reservoir Hosts | Geographic Distribution | Clinical Associations |
|---|---|---|---|
| B. afzelii | Rodents, small mammals | Europe, Asia | Skin manifestations (e.g., acrodermatitis chronica atrophicans) |
| B. garinii | Birds | Europe, Asia | Neuroborreliosis |
| B. burgdorferi sensu stricto | Various mammals | North America, Europe | Lyme arthritis |
| B. valaisiana | Birds | Europe, Asia | Considered potentially pathogenic |
| B. lusitaniae | Lizards | Europe, Mediterranean | Rare human cases reported |
One of the biggest mysteries in Lyme disease research is why some patients continue to experience symptoms even after completing antibiotic treatment. While some medical authorities attribute this to "post-treatment Lyme disease syndrome," others wonder if certain Borrelia variants might have special abilities to survive antibiotic therapy.
In 2025, a team of Italian and Slovenian researchers designed an elegant experiment to investigate whether biofilm formation might explain these persistent infections 4 6 .
Biofilms are structured communities of bacteria encased in a protective matrix—essentially, fortified microbial cities that make bacteria remarkably resistant to antibiotics and immune attacks.
The research team hypothesized that genetic differences between Borrelia afzelii strains might influence their ability to form these protective structures.
7 Borrelia afzelii and 5 Borrelia garinii clinical isolates from patients with erythema migrans 4
Complete genetic blueprint of each strain using advanced sequencing technology 6
Measured extracellular DNA content and total biomass of biofilms 4
Compared MIC (Minimum Inhibitory Concentration) and MBIC (Minimum Biofilm Inhibitory Concentration)
The findings revealed fascinating differences between Borrelia afzelii and its close relatives:
Biofilm formation creates a protective fortress that shields bacteria from antibiotics that would normally kill them. This doesn't represent traditional antibiotic resistance but rather a physical barrier that prevents antibiotics from reaching their targets.
| Antibiotic | MIC (μg/mL) | MBIC (μg/mL) | Increase Required for Biofilms |
|---|---|---|---|
| Amoxicillin | 0.25 | 2 | 8-fold |
| Azithromycin | 0.125 | 2 | 16-fold |
| Ceftriaxone | 0.25 | 16 | 64-fold |
| Doxycycline | 0.5 | 32 | 64-fold |
Data source: 6
| Genomic Feature | B. afzelii vs. B. garinii | With B. burgdorferi Added |
|---|---|---|
| Core Genome | 38.9% shared | 26.1% shared |
| Cloud Genome | 34.4% | 53.4% |
| Unique Genes | 26.7% | 20.5% |
Data source: 6
Modern research into Borrelia afzelii variants relies on sophisticated laboratory tools that allow scientists to examine the genetic makeup of these elusive bacteria. The Italian and Slovenian research team used several cutting-edge techniques and reagents to conduct their experiment 4 6 :
This technology enables researchers to read the complete DNA sequence of each bacterial strain, identifying even minute genetic differences between variants.
Specialized computer programs that help analyze and compare the massive amounts of genetic data generated by sequencing.
Comprehensive databases that help researchers determine whether genetic differences might confer antibiotic resistance.
A specially formulated growth medium that mimics the natural environment Borrelia bacteria need to survive and multiply in the laboratory.
A clever method that uses color changes to indicate bacterial growth, allowing researchers to test antibiotic effectiveness visually.
These tools have revolutionized our ability to study bacterial genetics, moving from observing general characteristics to examining the precise molecular differences that make each variant unique.
The discovery that different genetic variants of Borrelia afzelii possess distinct biofilm-forming capabilities has profound implications for Lyme disease treatment. Rather than applying a one-size-fits-all approach to treatment, doctors may eventually be able to test which specific variant a patient has and prescribe antibiotics known to be more effective against that particular strain's characteristics.
Similarly, diagnostic tests are evolving to better detect these genetic variants. Traditional Lyme tests often miss early infections because they look for a limited set of bacterial markers. New approaches using multiple recombinant antigens or synthetic peptides can detect a wider range of variants, potentially leading to earlier and more accurate diagnosis 2 3 7 .
Accuracy of novel peptide panel in distinguishing between B. afzelii, B. garinii, and B. burgdorferi sensu stricto 3
As research progresses, we're moving toward a more nuanced understanding of Lyme disease that considers the genetic diversity of its causative agent. Future treatments might include:
That break down the protective matrix before antibiotic treatment
Tailored to a patient's particular infection
That quickly identify not just the presence of Borrelia, but its specific genetic variant
That reduce transmission of the most problematic variants
The story of Borrelia afzelii's genetic variants teaches us an important lesson about infectious diseases: the pathogens that challenge us are not static enemies but dynamic, evolving entities. Their genetic diversity, forged through countless generations of adaptation to different hosts and environments, represents both a challenge for medicine and a fascinating window into evolution in action.
As research continues to unravel the secrets of these genetic variants, we gain not just scientific knowledge but practical tools to combat Lyme disease more effectively. The same genetic diversity that makes Borrelia afzelii such a formidable opponent may eventually reveal its vulnerabilities—opening new avenues for treatment and prevention that respect the complex, ever-changing nature of this remarkable bacterium.