{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T23:15:21Z","timestamp":1777590921443,"version":"3.51.4"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T00:00:00Z","timestamp":1564617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["RD16\/0016\/0011"],"award-info":[{"award-number":["RD16\/0016\/0011"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Development Regional Fund","award":["S2017\/BMD-3691"],"award-info":[{"award-number":["S2017\/BMD-3691"]}]},{"name":"Comunidad de Madrid (Spain) and European Structural and Investment Funds"},{"name":"Spanish Ministry of Economy and Competitivity","award":["BIO2017-83128-R"],"award-info":[{"award-number":["BIO2017-83128-R"]}]},{"name":"FPI fellowship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To elucidate the potential mutation-driven mechanisms involved in the acquisition of tigecycline resistance by the opportunistic pathogen Stenotrophomonas maltophilia. The mutational trajectories and their effects on bacterial fitness, as well as cross-resistance and\/or collateral susceptibility to other antibiotics, were also addressed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>S. maltophilia populations were submitted to experimental evolution in the presence of increasing concentrations of tigecycline for 30\u2009days. The genetic mechanisms involved in the acquisition of tigecycline resistance were determined by WGS. Resistance was evaluated by performing MIC assays. Fitness of the evolved populations and individual clones was assessed by measurement of the maximum growth rates.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>All the tigecycline-evolved populations attained high-level resistance to tigecycline following different mutational trajectories, yet with some common elements. Among the mechanisms involved in low susceptibility to tigecycline, mutations in the SmeDEF efflux pump negative regulator smeT, changes in proteins involved in the biogenesis of the ribosome and modifications in the LPS biosynthesis pathway seem to play a major role. Besides tigecycline resistance, the evolved populations presented cross-resistance to other antibiotics, such as aztreonam and quinolones, and they were hypersusceptible to fosfomycin, suggesting a possible combination treatment. Further, we found that the selected resistance mechanisms impose a relevant fitness cost when bacteria grow in the absence of antibiotic.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Mutational resistance to tigecycline was easily selected during exposure to this antibiotic. However, the fitness cost may compromise the maintenance of S. maltophilia tigecycline-resistant populations in the absence of antibiotic.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkz326","type":"journal-article","created":{"date-parts":[[2019,7,8]],"date-time":"2019-07-08T07:10:03Z","timestamp":1562569803000},"page":"3221-3230","source":"Crossref","is-referenced-by-count":19,"title":["Mechanisms and phenotypic consequences of acquisition of tigecycline resistance by Stenotrophomonas maltophilia"],"prefix":"10.1093","volume":"74","author":[{"given":"Paula","family":"Blanco","sequence":"first","affiliation":[{"name":"Centro Nacional de Biotecnolog\u00eda, CSIC, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando","family":"Corona","sequence":"additional","affiliation":[{"name":"Centro Nacional de Biotecnolog\u00eda, CSIC, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8813-7607","authenticated-orcid":false,"given":"Jos\u00e9 Luis","family":"Martinez","sequence":"additional","affiliation":[{"name":"Centro Nacional de Biotecnolog\u00eda, CSIC, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,8,1]]},"reference":[{"key":"2019101809591852000_dkz326-B1","doi-asserted-by":"crossref","first-page":"2276","DOI":"10.3389\/fmicb.2017.02276","article-title":"Stenotrophomonas maltophilia as an emerging ubiquitous pathogen: looking beyond contemporary antibiotic therapy","volume":"8","author":"Adegoke","year":"2017","journal-title":"Front Microbiol"},{"key":"2019101809591852000_dkz326-B2","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1007\/s10096-009-0709-5","article-title":"Community-acquired Stenotrophomonas maltophilia infections: a systematic 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