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

Abstract

24A basic feature of infection caused by Borrelia burgdorferi, the etiological agent 25 of Lyme borreliosis, is that persistent infection is the rule, not the norm, in its many hosts. 26 The ability to persist and evade host immune clearance poses a challenge to effective 27 antimicrobial treatment. A link between therapy failure and the presence of persister cells 28 has started to emerge. There is growing experimental evidence that viable, but non-29 cultivable spirochetes persist following treatment with several different antimicrobial 30 agents, then resurge after 12 months. The current study utilized the mouse model to 31 evaluate if persistence and resurgence occur following antimicrobial treatment in a 32 disease-susceptible (C3H/HeN) and disease-resistant (C57BL/6) mouse strain infected 33 with B. burgdorferi strains N40 and B31, to confirm the generality of these phenomena. 34 The status of infection was evaluated at 12 and 18-months after treatment. The results 35 demonstrated that persistent spirochetes remain viable for up to 18 months following 36 treatment, but divide slowly, thereby being tolerant to the effects of antimicrobial agents, 37 as well as being non-cultivable. The phenomenon of persistence and resurgence in 38 disease-susceptible C3H mice is equally evident in disease-resistant B6 mice, and not 39 unique to any particular B. burgdorferi strain. The results also demonstrate that following 40 antimicrobial treatment, both strains of B. burgdorferi, N40 and B31, lose one or more 41 small plasmids, resulting in attenuation. The biological relevance of attenuated B. 42 burgdorferi spirochetes is probably inconsequential. The study demonstrated that non-43 cultivable spirochetes can persist in a host following antimicrobial treatment for a long 44 time but did not demonstrate their clinical relevance in a mouse model of chronic 45 infection.