The bacteria behind Lyme disease belong to a group called Borrelia burgdorferi sensu lato, which contains more than 20 recognized genospecies, at least six or seven of which are confirmed to cause human illness. Within each of those species, researchers have cataloged dozens of genetically distinct strains using molecular typing methods. The number keeps growing as genomic tools improve and surveillance expands into new regions, so there is no single tidy count. But the diversity is real, and it shapes everything from the symptoms a patient develops to the chances of getting Lyme disease a second time.
Species Versus Strains
A common source of confusion is the difference between a Borrelia species and a Borrelia strain. Think of species as broad categories of the bacterium, each genetically distinct enough to be given its own scientific name. Within each species, individual isolates can differ in their surface proteins, plasmid content, and virulence genes, and those variants are what researchers call strains or genotypes. The entire group of Lyme-causing bacteria, Borrelia burgdorferi sensu lato, functions as an umbrella over all these species and their internal diversity.
The species confirmed to infect humans include B. burgdorferi sensu stricto (the dominant cause of Lyme in North America), B. afzelii and B. garinii (the two most common causes in Europe), B. bavariensis, B. spielmanii, B. lusitaniae, and the recently described B. mayonii. Several other genospecies have been found in ticks or animal reservoirs but are not yet clearly linked to human disease. The total species count in the sensu lato complex now exceeds 20, and new ones continue to be proposed as genetic sequencing becomes cheaper and more widely applied.
Why the Number Keeps Climbing
B. mayonii is a good example of how the list grows. It was formally described in 2016 after being detected in patients and Ixodes scapularis ticks in the upper midwestern United States. Genetic analysis placed it within the sensu lato complex but clearly separated it from B. burgdorferi sensu stricto, to which it is most closely related at roughly 95 percent sequence similarity across multiple housekeeping genes.1PubMed Central. Borrelia mayonii sp. nov., a member of the Borrelia burgdorferi sensu lato complex, detected in patients and ticks in the upper midwestern United States Whole-genome comparison later confirmed those taxonomic findings, showing less than 94 percent average nucleotide identity between B. mayonii and other sensu lato species.2PLOS ONE. Whole Genome Sequence and Comparative Genomics of the Novel Lyme Borreliosis Causing Pathogen, Borrelia mayonii B. mayonii causes unusually high levels of spirochetes in the blood and can produce a distinctive spreading rash that differs from the classic bull’s-eye pattern. Its discovery underscores that even in a well-studied region like the upper Midwest, new Lyme-causing species can go unnoticed for years.
The Geography of Lyme Diversity
If you live in North America, virtually all Lyme disease you hear about is caused by a single species, B. burgdorferi sensu stricto, with B. mayonii as a rare addition in Minnesota and Wisconsin. Europe is a different story. The two species responsible for most European infections, B. afzelii and B. garinii, are not found in the United States at all.3PubMed Central. Comparison of Lyme Disease in the United States and Europe This means the diversity of species causing human Lyme disease is substantially greater in Europe than in North America.
That geographic split has practical consequences. Because different species tend to favor different organs, the clinical profile of Lyme disease looks different on opposite sides of the Atlantic. European clinicians see conditions like acrodermatitis chronica atrophicans, a chronic skin disorder strongly linked to B. afzelii, that barely exists in the American medical literature. Meanwhile, Lyme arthritis, which is closely associated with B. burgdorferi sensu stricto, is far more common in the United States than in Europe.4Research in Microbiology. Association between different clinical manifestations of Lyme disease and different species of Borrelia burgdorferi sensu lato A traveler bitten by a tick in Germany could develop a disease that looks quite different from what a hiker contracts in Connecticut, even though both are broadly called Lyme disease.
Strain Diversity Within a Single Species
Even within B. burgdorferi sensu stricto, genetic variety is impressive. Researchers classify strains using several molecular typing systems. One approach sorts isolates into ribosomal spacer types (RST1, RST2, RST3). Another looks at the outer surface protein C gene, or ospC, which comes in at least 15 to 20 recognized major groups in North America alone.5PLOS ONE. Evidence for Host-Genotype Associations of Borrelia burgdorferi Sensu Stricto A third system, multilocus sequence typing, assigns each isolate a sequence type and groups related types into clonal complexes. Studies in the northeastern and upper midwestern United States have identified eleven or more major clonal complexes, and the number grows with each new survey.6PLOS ONE. Multilocus Sequence Typing of Borrelia burgdorferi Suggests Existence of Lineages with Differential Pathogenic Properties in Humans
These are not just academic categories. The typing systems overlap and reinforce each other, painting a picture of a pathogen population structured into distinct genetic lineages, each circulating among wildlife and ticks in the same forests at the same time. A single tick can carry more than one strain, and a single mouse can harbor several strains simultaneously.
Why Strain Type Matters for Symptoms
One of the most clinically relevant findings in recent Lyme research is that not all strains are equally aggressive. Within B. burgdorferi sensu stricto, RST1 strains carrying the ospC type A genotype trigger stronger inflammatory responses than RST2 or RST3 strains. When macrophages in laboratory experiments were exposed to RST1 isolates, they produced significantly higher levels of several inflammatory signaling molecules compared to cells exposed to RST3 isolates.7PubMed Central. Borrelia burgdorferi RST1 (OspC type A) genotype is associated with greater inflammation and more severe Lyme disease Patient data backed this up: RST1 infections were associated with more severe erythema migrans and a greater likelihood of Lyme arthritis.
In Europe, the picture is even more varied because the species themselves differ in tissue tropism. B. afzelii tends to stay in the skin, which is why it is linked to chronic skin manifestations. B. garinii has a stronger tendency to invade the nervous system, making it the species most frequently recovered from patients with Lyme neuroborreliosis. B. burgdorferi sensu stricto is the species most associated with joint involvement.4Research in Microbiology. Association between different clinical manifestations of Lyme disease and different species of Borrelia burgdorferi sensu lato So when someone asks “how many strains of Lyme disease are there,” the follow-up that really matters is: the strain you catch can shape which organs are affected and how sick you get.
Strain-Specific Immunity and Reinfection
People who have had Lyme disease and were treated with antibiotics can get it again, sometimes multiple times. This might suggest the immune system learns nothing from the first round, but the data tell a more nuanced story. When researchers analyzed patients who were reinfected, they found that the same strain was almost never responsible twice. Modeling based on real patient data from the northeastern United States suggested that treated patients develop protective immunity that is specific to the infecting strain and lasts for at least six years.8PubMed Central. Evidence for strain-specific immunity in patients treated for early lyme disease
The practical implication is straightforward: the large number of strains circulating in any given area means that even if your immune system effectively blocks the strain that made you sick, there are plenty of others it has never seen. A follow-up analysis estimated roughly a 25 percent reduction in the likelihood of detectable spirochetes in the blood during a second Lyme episode if the first infection was caused by one of the most common genotypes, consistent with partial, strain-targeted immunity.9PubMed Central. Public health impact of strain specific immunity to Borrelia burgdorferi You gain some protection, but not against the full roster of strains in your environment.
Multiple Strains in a Single Tick
A tick does not neatly carry one strain at a time. Studies of Ixodes ticks in nature routinely find multiple Borrelia strains coexisting in the same individual tick. In one analysis using high-resolution sequencing, coinfection with more than one ospC genotype was found in over half of the samples examined, with individual samples harboring anywhere from one to sixteen genotypes.10PubMed Central. Host adaptation drives genetic diversity in a vector-borne disease system Birds tended to carry more genotypes on average than mice, likely because birds feed a broader range of ticks across wider geographic areas.
This coinfection dynamic has implications beyond academic interest. When multiple strains compete for space inside a tick or a vertebrate host, the abundance of any one strain tends to drop as more strains pile in.11PubMed Central. Multistrain Infections with Lyme Borreliosis Pathogens in the Tick Vector Meanwhile, different transmission routes, including co-feeding (where ticks pass the bacterium among themselves on the same host without the host’s blood ever becoming systemically infected), help maintain strain diversity by giving rarer genotypes additional ways to persist.12PubMed Central. Co-feeding transmission facilitates strain coexistence in Borrelia burgdorferi, the Lyme disease agent The upshot is that the ecology actively promotes genetic variety rather than letting one dominant strain take over.
What Keeps So Many Strains in Circulation
One of the puzzles in Borrelia biology is why so many strains coexist in the same forests year after year. The leading explanation centers on a process called negative frequency-dependent selection acting on the ospC gene. In plain terms, the more common a particular ospC variant becomes, the more likely the local wildlife hosts are to have immune defenses against it, which drives its frequency back down and gives rarer variants an advantage. This cycle prevents any single strain from sweeping through the population and keeps the whole collection of genotypes in a rough equilibrium.13Genetics. Pervasive Recombination and Sympatric Genome Diversification Driven by Frequency-Dependent Selection in Borrelia burgdorferi, the Lyme Disease Bacterium
Recombination plays a supporting role. Borrelia does not swap DNA between cells as aggressively as many other bacteria, but the recombination that does occur is enough to reshuffle genetic material across strain lineages and prevent harmful mutations from accumulating. A prophage, essentially a virus embedded in the bacterial genome, exists in several forms within each cell and can transfer DNA between spirochetes, providing an additional if modest route for genetic mixing.14PubMed Central. Genetics of Borrelia burgdorferi The combined effect of balancing selection on surface proteins and limited but meaningful recombination produces the high sympatric diversity researchers observe in wild tick populations.
The Plasmid Factor
Borrelia burgdorferi has one of the most unusual genomes in the bacterial world. Its linear chromosome is accompanied by a large collection of linear and circular plasmids, small DNA elements that carry many of the genes most important for infecting hosts and evading the immune system. Different strains carry different complements of these plasmids, and plasmids can be lost when the bacterium is grown in the laboratory, which complicates research.15PubMed Central. Detection of established virulence genes and plasmids to differentiate Borrelia burgdorferi strains Because so many virulence factors are encoded on plasmids rather than the main chromosome, two strains that look similar by standard gene typing can behave quite differently in a host if they differ in their plasmid profiles.
One plasmid-borne gene that gets special attention is vlsE, which undergoes rapid antigenic variation during mammalian infection. Through a gene-conversion process, the bacterium shuffles segments from silent cassettes into the expressed vlsE gene, continuously altering the surface protein the immune system is trying to target.16PLoS Pathogens. Detailed Analysis of Sequence Changes Occurring during vlsE Antigenic Variation in the Mouse Model of Borrelia burgdorferi Infection This mechanism is one reason the spirochete can persist in a mammalian host for extended periods despite an active immune response, and it adds yet another layer of variation on top of the strain diversity that already exists in the wild population.
How Strain Diversity Complicates Vaccines
The only Lyme vaccine ever marketed for humans, LYMErix, targeted a single outer surface protein (OspA) from a single serotype. It was withdrawn from the market in 2002 for a mix of commercial and public-perception reasons, but its narrow coverage was also a scientific limitation: OspA comes in multiple serotypes, and different Borrelia species carry different ones. A vaccine protecting against just one serotype could not cover the full range of Lyme-causing bacteria, especially in Europe where species diversity is greater.
Current vaccine development efforts tackle this problem head-on. One approach constructs chimeric OspA proteins by swapping exposed amino acid residues from one serotype to another, creating single recombinant antigens that present epitopes from multiple serotypes at once. Proof-of-concept work with such chimeras demonstrated significant protection in mice against ticks carrying several OspA serotypes.17PubMed Central. Broadly Protective Multivalent OspA Vaccine against Lyme Borreliosis, Developed Based on Surface Shaping of the C-Terminal Fragment Another strategy uses OspA-ferritin nanoparticles, self-assembling protein structures that display OspA from six different serotypes simultaneously. In animal studies, this hexavalent formulation induced strong antibody responses against all six serotypes with no evidence of the components competing with each other.18npj Vaccines. Design of a broadly reactive Lyme disease vaccine Both strategies are explicitly designed around the reality that a single-serotype approach cannot address the pathogen’s diversity.
Borrelia miyamotoi and the Confusion Factor
To make things even more complicated, the same Ixodes ticks that carry Lyme Borrelia also transmit a related but biologically distinct spirochete called Borrelia miyamotoi. Despite being carried by the same ticks, B. miyamotoi is not a Lyme disease agent. It belongs to the relapsing fever group of Borrelia, a separate evolutionary lineage that typically spreads through soft-bodied ticks or lice.19PubMed Central. Borrelia miyamotoi infection in nature and in humans It causes a febrile illness that can mimic early Lyme disease, with fever, headache, and fatigue, but without the characteristic erythema migrans rash.
Standard two-tier Lyme testing does not reliably detect B. miyamotoi infection, since the antigens used are tailored to the Lyme group. Research into species-specific diagnostic markers has identified a protein called BipM that reacts with serum from B. miyamotoi-infected animals but not with serum from B. burgdorferi-infected mice or most human Lyme patients.20PubMed. Borrelia miyamotoi BipA-like protein, BipM, is a candidate serodiagnostic antigen distinguishing between Lyme disease and relapsing fever Borrelia infections If you are bitten by a deer tick and develop flu-like symptoms without a rash, B. miyamotoi is worth considering alongside Lyme, anaplasmosis, and babesiosis as possible culprits. It is not a “strain” of Lyme disease, but it rides the same vector and occupies the same geographic range, so patients and clinicians encounter it in the same situations.
Uncertainties and Ongoing Questions
Despite decades of research, several key questions remain open. Scientists still debate exactly how differences in genotype translate into differences in disease severity in real-world patients, as opposed to laboratory cell cultures. Experts have identified the pathogenicity of different B. burgdorferi genotypes for humans as one of the critical gaps in the field.21PubMed Central. Lyme disease ecology in a changing world: consensus, uncertainty and critical gaps for improving control The evidence linking RST1 strains to worse outcomes is among the strongest available, but a comprehensive map of genotype-to-clinical-outcome relationships across all species and all strain types does not yet exist.
Range expansion adds another layer of unpredictability. As tick habitat shifts with warming temperatures and changes in deer and rodent populations, Borrelia strains that were previously confined to small pockets may encounter new host communities and new tick populations. Whether this will increase or decrease the genetic diversity patients are exposed to in any given area is genuinely uncertain, and the ecological models needed to predict it rely on factors like deer density and host community composition that are themselves poorly quantified. For a person trying to protect themselves, the practical message remains the same regardless of how many strains are out there: tick avoidance, prompt removal, and awareness that Lyme can look different depending on where in the world you were bitten.