{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:46:50Z","timestamp":1785415610096,"version":"3.56.0"},"reference-count":48,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Macrolide resistance in\n                      <jats:italic toggle=\"yes\">Mycoplasma pneumoniae<\/jats:italic>\n                      is becoming prevalent. Tetracyclines are an important alternative for patients with macrolide-resistant\n                      <jats:italic toggle=\"yes\">M. pneumoniae<\/jats:italic>\n                      infections. Tetracycline-resistant\n                      <jats:italic toggle=\"yes\">M. pneumoniae<\/jats:italic>\n                      has never been reported in clinical isolates or\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      -induced strains. Here, we aimed to explore tetracycline-resistant\n                      <jats:italic toggle=\"yes\">M. pneumoniae in vitro<\/jats:italic>\n                      and the underlying resistance mechanisms. Clinically isolated parental\n                      <jats:italic toggle=\"yes\">M. pneumoniae<\/jats:italic>\n                      strains were selected for tetracycline resistance by inducing them\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      with increasing concentrations of tetracycline, minocycline, and tigecycline. The whole genomes of the induced resistant and parent strains were both sequenced to identify tetracycline-resistance genes, and their 16S rRNA gene sequences were compared. Ribosome-binding assays were conducted by incubating the 30S ribosomes of the resistant and sensitive strains with various concentrations of\n                      <jats:sup>3<\/jats:sup>\n                      H-labeled tetracycline. The effect of efflux pump inhibitor reserpine on the susceptibility of tetracyclines to the resistant mutants was evaluated. Eight resistant mutants were obtained from 12 tetracycline-susceptible\n                      <jats:italic toggle=\"yes\">M. pneumoniae<\/jats:italic>\n                      strains. Whole-genome sequencing identified point mutations in the 16S rRNA gene of all the resistant mutants. The ribosomes of two induced resistant strains showed lower tetracycline-binding capacities than their parental strains. Reserpine increased the susceptibility of two resistant mutants to tetracyclines by more than fourfold. None of the resistant mutants carried the known tetracycline-resistance genes.\n                      <jats:italic toggle=\"yes\">M. pneumoniae<\/jats:italic>\n                      strains can develop tetracycline resistance. Mutations in the 16S rRNA gene leading to decreased ribosomal-binding capacity and the presence of efflux pumps may be the mechanisms associated with tetracycline resistance in\n                      <jats:italic toggle=\"yes\">M. pneumoniae<\/jats:italic>\n                      . This study identifies markers to track the emergence of tetracycline resistance in\n                      <jats:italic toggle=\"yes\">M. pneumoniae<\/jats:italic>\n                      .\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Resistance to anti-\n                        <jats:italic toggle=\"yes\">Mycoplasma pneumoniae<\/jats:italic>\n                        antibiotics is a global public health problem. Effective antibiotic treatment strategies are urgently needed. Tetracyclines are among the most commonly used antibiotics for the treatment of drug-resistant\n                        <jats:italic toggle=\"yes\">M. pneumoniae<\/jats:italic>\n                        infections. Tetracycline-resistant\n                        <jats:italic toggle=\"yes\">M. pneumoniae<\/jats:italic>\n                        has not been reported; however, treatment with increased concentrations of tetracycline selects hyposensitive mutants. In this study, we successfully induced tetracycline-resistant\n                        <jats:italic toggle=\"yes\">M. pneumoniae<\/jats:italic>\n                        mutants by 10-month\n                        <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                        serial passage experiments and found that a 16S rRNA mutation resulting in reduced ribosomal drug binding was the mechanism that led to tetracycline resistance in\n                        <jats:italic toggle=\"yes\">M. pneumoniae<\/jats:italic>\n                        . In addition, the efflux pump might also be related to decreased tetracycline susceptibility. This study presented the first data on the induction of tetracycline resistance in\n                        <jats:italic toggle=\"yes\">M. pneumoniae in vitro<\/jats:italic>\n                        , providing insights into the development of effective treatment strategies for drug-resistant\n                        <jats:italic toggle=\"yes\">M. pneumoniae<\/jats:italic>\n                        infections in the future.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.03398-24","type":"journal-article","created":{"date-parts":[[2025,5,23]],"date-time":"2025-05-23T09:00:32Z","timestamp":1747990832000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["Evolution and characteristics of tetracycline resistance in\n                    <i>Mycoplasma pneumoniae<\/i>"],"prefix":"10.1128","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-3020-9083","authenticated-orcid":true,"given":"Panpan","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Respiratory and Critical Care Medicine, Senior Department of Infectious Diseases, The Fifth Medical Center of PLA General Hospital","place":["Beijing, China"]},{"name":"Senior Department of Infectious Diseases, The Fifth Medical Center of PLA General Hospital, National Clinical Research Center for Infectious Diseases","place":["Beijing, China"]},{"id":[{"id":"https:\/\/ror.org\/03xb04968","id-type":"ROR","asserted-by":"publisher"}],"name":"Anhui Medical University","place":["Hefei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Unit, Hainan Hospital of PLA General Hospital","place":["Sanya, 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