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Here we demonstrate that targeting the RNase that degrades R-loops, which cause DNA breaks, exacerbates the cost of resistance. Consequently, lack of RNase HI function drives resistant clones to extinction in populations with high initial frequency of resistance, both in laboratory conditions and in a mouse model of gut colonization. Thus, RNase HI provides a target specific against resistant bacteria, which we validate using a repurposed drug. In summary, we revealed key mechanisms underlying the cost of antibiotic resistance that can be exploited to specifically eliminate resistant bacteria.<\/jats:p>","DOI":"10.1101\/756767","type":"posted-content","created":{"date-parts":[[2019,9,5]],"date-time":"2019-09-05T15:25:11Z","timestamp":1567697111000},"source":"Crossref","is-referenced-by-count":0,"title":["DNA breaks-mediated cost reveals RNase HI as a new target for selectively eliminating antibiotic resistance"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8042-6201","authenticated-orcid":false,"given":"Roberto","family":"Balbont\u00edn","sequence":"first","affiliation":[]},{"given":"Nelson","family":"Fraz\u00e3o","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1622-5143","authenticated-orcid":false,"given":"Isabel","family":"Gordo","sequence":"additional","affiliation":[]}],"member":"54368","reference":[{"key":"2020020508150822000_756767v4.1","unstructured":"Global antimicrobial resistance surveillance system (GLASS) report: early implementation 2017-2018. 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