The generality of post-antimicrobial treatment persistence of replicatively-attenuatedBorrelia burgdorferiin a mouse model

Abstract

ABSTRACTA basic feature of infection caused byBorrelia burgdorferi, the etiological agent of Lyme borreliosis, is that persistent infection is the rule, not the norm, in its many hosts. The ability to persist and evade host immune clearance poses a challenge to effective antimicrobial treatment. A link between therapy failure and the presence of persister cells has started to emerge. There is growing experimental evidence that viable, but non-cultivable spirochetes persist following treatment with several different antimicrobial agents, then resurge after 12 months. The current study utilized the mouse model to evaluate if persistence and resurgence occur following antimicrobial treatment in a disease-susceptible (C3H/HeN) and disease-resistant (C57BL/6) mouse strain infected withB. burgdorferistrains N40 and B31, to confirm the generality of these phenomena. The status of infection was evaluated at 12 and 18-months after treatment. The results demonstrated that persistent spirochetes remain viable for up to 18 months following treatment, but divide slowly, thereby being tolerant to the effects of antimicrobial agents, as well as being non-cultivable. The phenomenon of persistence and resurgence in disease-susceptible C3H mice is equally evident in disease-resistant B6 mice, and not unique to any particularB. burgdorferistrain. The results also demonstrate that following antimicrobial treatment, both strains ofB. burgdorferi, N40 and B31, lose one or more small plasmids, resulting in attenuation. The biological relevance of attenuatedB. burgdorferispirochetes is probably inconsequential. The study demonstrated that non-cultivable spirochetes can persist in a host following antimicrobial treatment for a long time but did not demonstrate their clinical relevance in a mouse model of chronic infection.