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Treating Lyme disease during its initial stages with traditional tetracycline antibiotics is effective. However, 10\u201320% of patients treated with antibiotic therapy still shows prolonged symptoms of fatigue, musculoskeletal pain, and perceived cognitive impairment. When these symptoms persists for more than 6 months to years after completing conventional antibiotics treatment are called post-treatment Lyme disease syndrome (PTLDS). Though the exact reason for the prolongation of post treatment symptoms are not known, the growing evidence from recent studies suggests it might be due to the existence of drug-tolerant persisters. In order to identify effective drug molecules that kill drug-tolerant <jats:italic>borrelia<\/jats:italic> we have tested two antibiotics, azlocillin and cefotaxime that were identified by us earlier. The <jats:italic>in vitro<\/jats:italic> efficacy studies of azlocillin and cefotaxime on drug-tolerant persisters were done by semisolid plating method. The results obtained were compared with one of the currently prescribed antibiotic doxycycline. We found that azlocillin completely kills late log phase and 7\u201310 days old stationary phase <jats:italic>B. burgdorferi<\/jats:italic>. Our results also demonstrate that azlocillin and cefotaxime can effectively kill <jats:italic>in vitro<\/jats:italic> doxycycline-tolerant <jats:italic>B. burgdorferi<\/jats:italic>. Moreover, the combination drug treatment of azlocillin and cefotaxime effectively killed doxycycline-tolerant <jats:italic>B. burgdorferi<\/jats:italic>. Furthermore, when tested <jats:italic>in vivo<\/jats:italic>, azlocillin has shown good efficacy against <jats:italic>B. burgdorferi<\/jats:italic> in mice model. These seminal findings strongly suggests that azlocillin can be effective in treating <jats:italic>B. burgdorferi sensu stricto JLB31<\/jats:italic> infection and furthermore in depth research is necessary to evaluate its potential use for Lyme disease therapy.<\/jats:p>","DOI":"10.1038\/s41598-020-59600-4","type":"journal-article","created":{"date-parts":[[2020,3,2]],"date-time":"2020-03-02T11:03:15Z","timestamp":1583146995000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Azlocillin can be the potential drug candidate against drug-tolerant Borrelia burgdorferi sensu stricto JLB31"],"prefix":"10.1038","volume":"10","author":[{"given":"Venkata Raveendra","family":"Pothineni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hari-Hara S. 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