{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T23:51:40Z","timestamp":1789689100704,"version":"4.0.1"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T00:00:00Z","timestamp":1654214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Tigecycline is one of important antimicrobial agents for the treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria. However, the emergence and prevalence of plasmid-mediated tigecycline resistance gene <jats:italic>tet<\/jats:italic>(X4) are threatening human and animal health. Fitness cost elicited by resistance plasmids is a key factor affecting the maintenance and transmission of antibiotic resistance genes (ARGs) in the host. A comparative analysis of the fitness cost of different types of <jats:italic>tet<\/jats:italic>(X4)-positive plasmids is helpful to understand and predict the prevalence of dominant plasmids. In this study, we performed a large-scale analysis of fitness cost of <jats:italic>tet<\/jats:italic>(X4)-positive plasmids origin from clinical isolates. These plasmids were successfully electroporated into a reference strain <jats:italic>Escherichia coli<\/jats:italic> TOP10, and a series of transformants carrying the <jats:italic>tet<\/jats:italic>(X) gene were obtained. The effects of <jats:italic>tet<\/jats:italic>(X4)-positive plasmids on the growth rate, plasmid stability, relative fitness, biofilm formation, and virulence in a <jats:italic>Galleria mellonella<\/jats:italic> model were evaluated. Consequently, we found that these plasmids resulted in varying degrees of fitness cost on TOP10, including delayed bacterial growth and attenuated virulence. Out of these plasmids, <jats:italic>tet<\/jats:italic>(X4)-harboring IncFII plasmids showed the lowest fitness cost on the host. Furthermore, by means of experimental evolution in the presence of commonly used drugs in clinic, the fitness cost of <jats:italic>tet<\/jats:italic>(X4)-positive plasmids was substantially alleviated, accompanied by increased plasmid stability. Collectively, our data reveal the differential fitness cost caused by different types of <jats:italic>tet<\/jats:italic>(X4)-positive plasmids and suggest that the wide use of tetracycline antibiotics may promote the evolution of plasmids.<\/jats:p>","DOI":"10.3389\/fcimb.2022.798802","type":"journal-article","created":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T05:50:06Z","timestamp":1654235406000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Large-Scale Analysis of Fitness Cost of tet(X4)-Positive Plasmids in Escherichia coli"],"prefix":"10.3389","volume":"12","author":[{"given":"Feifei","family":"Tang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijie","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1186\/s12879-021-06338-7","article-title":"Evaluating the Performance Characteristics of Different Antimicrobial Susceptibility Testing Methodologies for Testing Susceptibility of Gram-Negative Bacteria to Tigecycline","volume":"21","author":"Babaei","year":"2021","journal-title":"BMC Infect. 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