The Emerging Role of Microbial Biofilm in Lyme Neuroborreliosis

Abstract

Lyme borreliosis (LB) is the most common tick-borne disease caused by the spirochete Borrelia burgdorferi in North America and Borrelia afzelii or Borrelia garinii in Europe and Asia, respectively. The infection affects multiple organ systems, including the skin, joints, and the nervous system. Lyme neuroborreliosis (LNB) is the most dangerous manifestation of Lyme disease, occurring in 10-15% of infected individuals. During the course of the infection, bacteria migrate through the host tissues altering the coagulation and fibrinolysis pathways and the immune response, reaching the central nervous system (CNS) within 2 weeks after the bite of an infected tick. The early treatment with oral antimicrobials is effective in the majority of patients with LNB. Nevertheless, persistent forms of LNB are relatively common, despite targeted antibiotic therapy. It has been observed that the antibiotic resistance and the reoccurrence of Lyme disease are associated with biofilm-like aggregates in B. burgdorferi, B. afzelii, and B. garinii, both in vitro and in vivo, allowing Borrelia spp. to resist to adverse environmental conditions. Indeed, the increased tolerance to antibiotics described in the persisting forms of Borrelia spp., is strongly reminiscent of biofilm growing bacteria, suggesting a possible role of biofilm aggregates in the development of the different manifestations of Lyme disease including LNB.

Keywords: Borrelia; biofilm; erythema migrans; lyme; neuroborreliosis; skin.

Figure 1

(A) Confocal microscopy images of B. burgdorferi B31 strain (American Type Tissue Collection 35210) biofilms. Upper panel show the X-Y planes (top view), while the lower panel show the Z section (side view). The sample was stained with BacLight Live/Dead (Invitrogen Life Technologies, Carlsbad, CA, USA) (188). Representative images of biofilms developed on polystyrene pegs following 72 h incubation at 37°C. Spirochetes were grown in a μ-Slide 8-well system (ibidi, Germany) and cultured in BSK-H medium containing 6% rabbit serum (Sigma-Aldrich). (B) Schematic representation of a B. burgdorferi biofilm. The biofilm matrix produced by spirochetes (green) provides shelter from host defenses, and reduces the diffusion of antibiotics. Persister forms of B. burgdorferi (in blue), exhibit multidrug tolerance and are likely responsible for the recalcitrance of chronic LB. The illustration is adapted from Mind the Graph (https://mindthegraph.com) under the Creative Commons License.