Biofilm/Persister/Stationary Phase Bacteria Cause More Severe Disease Than Log Phase Bacteria – I Biofilm Borrelia burgdorferi Not Only Display More Tolerance to Lyme Antibiotics But Also Cause More Severe Pathology In a Mouse Arthritis Model: Implications for Understanding Persistence, PTLDS and Treatment Failure

摘要: Abstract Lyme disease, caused by Borrelia burgdorferi, is the most common tick-borne illness in US and Europe. While patients can be cured with a 2-4 week antibiotic therapy, about 10%-20% continue to suffer persistent symptoms of fatigue, pain or joint muscle aches, neurocognitive despite treatment, condition called post-treatment disease syndrome (PTLDS). The cause for PTLDS unclear but one possibility infection B. burgdorferi. burgdorferi known develop morphological variant forms such as round bodies aggregated biofilm-like microcolonies log phase culture consisting spirochete form grows into stationary phase. Here we isolated microcolony planktonic (spirochetal body) from found that (SP) (MC) were much more tolerant current antibiotics doxycycline, ceftriaxone cefuroxime than (LOG). In addition, also compared ability mouse arthritis model. Surprisingly, MC particular SP severe an earlier onset inflammation swelling LOG. MC-infected mice showed significant early 9 days post-infection, while LOG did not swelling. At 21 days, group dramatically increased peaked, at this time less group. infected just beginning 21-day only slight 30-day post infection, developed similar severity group, still show However, 35-day all three groups degree Thereafter, waxed waned during 90-day observation. Thus, established new biofilm-inocula mediated visual model could facilitate efficient evaluation treatment regimens infections. Our findings provide insight pathogenesis may have implications understanding failure, due possible biofilm inoculation tick-bite. This biofilm/persister seeding valid different microbial infections developing effective treatments general.