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When treated early, the disease usually resolves, but when left untreated, it can result in symptoms such as arthritis and encephalopathy. Treatment of the late-stage disease may require multiple courses of antibiotic therapy. Given that antibiotic resistance has not been observed for\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. burgdorferi<\/jats:named-content>\n            , the reason for the recalcitrance of late-stage disease to antibiotics is unclear. In other chronic infections, the presence of drug-tolerant persisters has been linked to recalcitrance of the disease. In this study, we examined the ability of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. burgdorferi<\/jats:named-content>\n            to form persisters. Killing growing cultures of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. burgdorferi<\/jats:named-content>\n            with antibiotics used to treat the disease was distinctly biphasic, with a small subpopulation of surviving cells. Upon regrowth, these cells formed a new subpopulation of antibiotic-tolerant cells, indicating that these are persisters rather than resistant mutants. The level of persisters increased sharply as the culture transitioned from the exponential to stationary phase. Combinations of antibiotics did not improve killing. Daptomycin, a membrane-active bactericidal antibiotic, killed stationary-phase cells but not persisters. Mitomycin C, an anticancer agent that forms adducts with DNA, killed persisters and eradicated growing and stationary cultures of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. burgdorferi<\/jats:named-content>\n            . Finally, we examined the ability of pulse dosing an antibiotic to eliminate persisters. After addition of ceftriaxone, the antibiotic was washed away, surviving persisters were allowed to resuscitate, and the antibiotic was added again. Four pulse doses of ceftriaxone killed persisters, eradicating all live bacteria in the culture.\n          <\/jats:p>","DOI":"10.1128\/aac.00864-15","type":"journal-article","created":{"date-parts":[[2015,5,27]],"date-time":"2015-05-27T15:24:53Z","timestamp":1432740293000},"page":"4616-4624","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":157,"title":["Borrelia burgdorferi, the Causative Agent of Lyme Disease, Forms Drug-Tolerant Persister Cells"],"prefix":"10.1128","volume":"59","author":[{"given":"Bijaya","family":"Sharma","sequence":"first","affiliation":[{"name":"Antimicrobial Discovery Center and Department of Biology, Northeastern University, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Autumn V.","family":"Brown","sequence":"additional","affiliation":[{"name":"Antimicrobial Discovery Center and Department of Biology, Northeastern University, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole E.","family":"Matluck","sequence":"additional","affiliation":[{"name":"Antimicrobial Discovery Center and Department of Biology, Northeastern University, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linden T.","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Lewis","sequence":"additional","affiliation":[{"name":"Antimicrobial Discovery Center and Department of Biology, Northeastern University, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/314727"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.112408.134306"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.8.4329"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.11.6339-6345.2002"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1462-5822.2004.00367.x"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01651-09"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00860-09"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1244705"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2236"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciu397"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200107123450207"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-157-3-201208070-01002"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2007.12.014"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-107-5-725"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22131"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1086\/508667"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.10.5759-5767.2004"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000293"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2714"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1000317"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2013.08.045"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1100186108"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2651"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.3390\/toxins6031002"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki201"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.25.13865"},{"key":"e_1_3_2_28_2","first-page":"253","article-title":"Electrotransformation of the spirochete Borrelia burgdorferi","volume":"47","author":"Samuels DS","year":"1995","unstructured":"Samuels DS. 1995. 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