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Understanding these compensatory mechanisms allows for informed treatment strategies, and could lead to the development of improved therapeutics. To this end, studies were performed to determine whether <jats:italic>Borrelia burgdorferi<\/jats:italic>, the spirochetal agent of Lyme disease, also exhibits genetically-encoded responses to the commonly prescribed antibiotics doxycycline and amoxicillin. After culturing for 24 h in a sublethal concentration of doxycycline, there were significant increases in a substantial number of transcripts for proteins that are involved with translation. In contrast, incubation with a sublethal concentration of amoxicillin did not lead to significant changes in levels of any bacterial transcript. We conclude that <jats:italic>B<\/jats:italic>. <jats:italic>burgdorferi<\/jats:italic> has a mechanism(s) that detects translational inhibition by doxycycline, and increases production of mRNAs for proteins involved with translation machinery in an attempt to compensate for that stress.<\/jats:p>","DOI":"10.1371\/journal.pone.0274125","type":"journal-article","created":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T17:36:07Z","timestamp":1664559367000},"page":"e0274125","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Borrelia burgdorferi, the Lyme disease spirochete, possesses genetically-encoded responses to doxycycline, but not to amoxicillin"],"prefix":"10.1371","volume":"17","author":[{"given":"Timothy C.","family":"Saylor","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1954-2443","authenticated-orcid":true,"given":"Timothy","family":"Casselli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn G.","family":"Lethbridge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessamyn P.","family":"Moore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie M.","family":"Owens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine A.","family":"Brissette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfram R.","family":"Z\u00fcckert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2406-4776","authenticated-orcid":true,"given":"Brian","family":"Stevenson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,9,30]]},"reference":[{"key":"pone.0274125.ref001","doi-asserted-by":"crossref","first-page":"16090","DOI":"10.1038\/nrdp.2016.90","article-title":"Lyme borreliosis","volume":"2","author":"AC Steere","year":"2016","journal-title":"Nat Rev Dis Primers"},{"key":"pone.0274125.ref002","doi-asserted-by":"crossref","first-page":"m1041","DOI":"10.1136\/bmj.m1041","article-title":"Lyme borreliosis: diagnosis and management","volume":"369","author":"BJ Kullberg","year":"2020","journal-title":"Brit Med J"},{"key":"pone.0274125.ref003","first-page":"993","article-title":"Three sudden cardiac deaths associated with Lyme carditis\u2014United States, November 2012-July 2013","volume":"62","author":"Centers for Disease Control and Prevention","year":"2013","journal-title":"Morb Mortal Wkly Rep"},{"key":"pone.0274125.ref004","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1086\/508667","article-title":"The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: Clinical practice guidelines by the Infectious Diseases Society of America","volume":"43","author":"GP Wormser","year":"2006","journal-title":"Clin Infect Dis"},{"key":"pone.0274125.ref005","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1001\/jama.2016.2884","article-title":"Diagnosis, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: a review","volume":"315","author":"E Sanchez","year":"2016","journal-title":"JAMA"},{"key":"pone.0274125.ref006","unstructured":"Centers for Disease Control and Prevention. 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