Borrelia burgdorferi is the bacterial species responsible for causing Lyme disease, the most common vector-borne illness in the Northern Hemisphere. This organism is a spirochete, characterized by its distinct, coil-shaped body. The unique mechanisms B. burgdorferi uses to navigate hosts, evade the immune system, and adapt its genetic makeup make it a complex and successful pathogen. Understanding its biology provides insight into the challenges of preventing and treating Lyme disease.
Distinct Morphology and Motility
Borrelia burgdorferi possesses an unusual physical structure integral to its ability to cause infection. The organism has a flexible, helical shape, but it is not a rigid spiral like some other bacteria. Instead, it exhibits a “flat-wave” morphology, allowing it to move in a distinct, undulating manner.
The mechanism for this unique movement is the periplasmic flagella, located between the inner cell membrane and the outer membrane sheath. A bundle of seven to eleven flagella are attached at each end of the cell cylinder, wrapping around the spirochete’s main body. The rotation of these internal flagella generates a propelling force that causes the entire cell to flex and twist.
This sheltered, corkscrew-like movement is highly effective for navigating the dense, gel-like environment of host tissues. While the motility of most bacteria is inhibited by viscous media, B. burgdorferi’s internal flagella allow it to bore through connective tissues, such as collagen. This ability is necessary for its dissemination from the initial tick bite site to distant organs like the joints and heart. The flagella also contribute to maintaining the cell’s unique flat-wave shape, giving them a skeletal function in addition to their role in motility.
The Complex Life Cycle and Transmission
The survival of B. burgdorferi depends on a complex life cycle involving an arthropod vector and a vertebrate host. The primary vector in North America is the blacklegged tick, Ixodes scapularis, which transmits the spirochete during a blood meal. The bacterium cycles between these ticks and various reservoir hosts, such as small mammals (mice) and birds.
Transmission to a human or other mammal occurs only after the infected tick has been attached and feeding for a necessary period. In the unfed tick, the spirochetes reside in the midgut and express Outer Surface Protein A (OspA). The initiation of the blood meal triggers a change in the bacterium’s gene expression as it senses the mammalian host environment.
The spirochetes downregulate OspA and upregulate Outer Surface Protein C (OspC), necessary for survival in the mammalian host. This change in surface proteins allows the spirochetes to exit the tick’s midgut, migrate to the salivary glands, and be transmitted into the host’s skin via the tick’s saliva. This environmental sensing and protein switching is a carefully timed event that determines the success of the infection.
Evasion and Persistence in the Host
Once B. burgdorferi enters the mammalian host, it must survive the immune response, a feat achieved through multiple evasion strategies. One primary defense mechanism is the subversion of the host’s complement system, a rapid, first-line innate immune defense. The spirochete produces surface proteins that bind to host complement-regulatory factors, such as Factor H.
By recruiting these host proteins, the bacterium effectively turns off the complement cascade on its surface, preventing complement-mediated destruction. Specific proteins, like BBK32, can also inhibit the classical complement pathway by binding to components like C1r, halting the entire cascade. The ability of different Borrelia strains to evade the complement of various host species correlates strongly with their ability to infect and persist, which helps define the pathogen’s host tropism.
Furthermore, the bacterium establishes tissue tropism, preferentially migrating to and colonizing immune-privileged sites. These sites include the joints, the nervous system, and the heart, where immune surveillance is naturally reduced. The resulting symptoms of Lyme disease, such as arthritis and neurological issues, are often the consequence of persistent bacterial presence and the host’s sustained inflammatory reaction.
Genetic Flexibility and Antigenic Variation
The long-term persistence of B. burgdorferi in the face of an adaptive immune response is made possible by its unique and flexible genome. Unlike most bacteria that have a single circular chromosome, B. burgdorferi possesses a linear chromosome and a large collection of linear and circular plasmids. These plasmids carry many of the genes responsible for host adaptation and survival, including those encoding Outer Surface Proteins (Osp).
The most significant mechanism of immune evasion is antigenic variation, which involves the continuous switching of surface protein expression to evade antibody recognition. The vls system, located on a linear plasmid, is a complex genetic locus that drives this process. This locus contains a single expressed gene, vlsE, and multiple silent vls cassettes.
During infection in the mammalian host, segments of the silent cassettes recombine into the active vlsE expression site through gene conversion. This recombination constantly changes the structure of the VlsE surface lipoprotein, generating antigenic variants. By continually changing its surface appearance, the bacterium stays one step ahead of the host’s adaptive immune system, enabling it to establish a persistent infection.