{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:11:43Z","timestamp":1787026303103,"version":"build-2736575974"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T00:00:00Z","timestamp":1767916800000},"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:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      After a prolonged lull during COVID-19 non-pharmaceutical interventions,\n                      <jats:italic>Mycoplasma pneumoniae<\/jats:italic>\n                      activity re-emerged in 2023 in multiple regions; in China this occurred against a backdrop of very high macrolide resistance. We conducted a retrospective single-center study of pediatric\n                      <jats:italic>M. pneumoniae<\/jats:italic>\n                      pneumonia in Jinan, comparing a pre-resurgence period (2021) with 2023\u20132024.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Clinical data were linked to whole-genome sequencing of 227 cultured isolates. We assessed lineage composition and relatedness using core-genome phylogenetics and SNP-threshold networks, and compared diversity and pan-genome functional profiles across major clades. Phenotypic antimicrobial susceptibility testing was performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The proportion of severe cases increased from 7.4% (2021) to 19.9% (2024). Over the same interval, the P1-1\/ST3 lineage rose from 41.9% to 84.0%, displacing previously co-circulating lineages. Core-genome analyses indicated reduced diversity and a compact ST3 cluster within the T1-3R subclade of the P1-type 1 lineage (EC1 clone), alongside a smaller P1-type 2\/T2-2 (EC2\/ST14) clade. Using a \u226411-SNP threshold, 74% of isolates fell within the largest connected component. Pan-genome comparisons suggested enrichment of replication\/recombination\/repair functions in T1-3R, whereas canonical adhesion factors and the CARDS toxin were conserved. All isolates carried the 23S rRNA A2063G substitution with phenotypic macrolide resistance, while\n                      <jats:italic>in vitro<\/jats:italic>\n                      susceptibility to tetracycline and levofloxacin was retained.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The 2023\u20132024 resurgence coincided with clonal replacement by P1-1\/ST3 in a setting of fixed macrolide resistance and an increase in severe pediatric disease. Given the retrospective, culture-based design, this should be interpreted as a temporal association rather than evidence that ST3 intrinsically caused more severe disease. These findings support consideration of non-macrolide agents in similar high-resistance settings and motivate prospective genomic-clinical surveillance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2025.1732239","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T06:41:35Z","timestamp":1767940895000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Clonal replacement by a P1-1\/ST3 lineage in pediatric Mycoplasma pneumoniae, Jinan, China, 2021\u20132024"],"prefix":"10.3389","volume":"15","author":[{"given":"Ming","family":"Fang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianmei","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijian","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ti","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaning","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zengqiang","family":"Kou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3195","DOI":"10.1128\/JCM.01301-15","article-title":"Development of a multilocus sequence typing scheme for the molecular typing of Mycoplasma pneumoniae","volume":"53","author":"Brown","year":"2015","journal-title":"J. Clin. Microbiol."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.00157","article-title":"Mycoplasma pneumoniae epidemiology in England and Wales: a national perspective","volume":"7","author":"Brown","year":"2016","journal-title":"Front. Microbiol."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1449511","article-title":"Increased macrolide resistance rate of Mycoplasma pneumoniae correlated with epidemic in Beijing, China in 2023","volume":"15","author":"Chen","year":"2024","journal-title":"Front. Microbiol."},{"key":"B4","volume-title":"Methods for Antimicrobial Susceptibility Testing for Human Mycoplasmas; Approved Guideline. CLSI document M43-A","year":"2011"},{"key":"B5","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1016\/j.idnow.2021.05.004","article-title":"Pediatric Infectious Disease Group (GPIP) position paper on the immune debt of the COVID-19 pandemic in childhood, how can we fill the immunity gap","volume":"51","author":"Cohen","year":"2021","journal-title":"Infect. Dis. Now"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e15","DOI":"10.1093\/nar\/gku1196","article-title":"Rapid phylogenetic analysis of large samples of recombinant bacterial whole-genome sequences using Gubbins","volume":"43","author":"Croucher","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"149","DOI":"10.15585\/mmwr.mm7307a3","article-title":"Notes from the field: reemergence of Mycoplasma pneumoniae infections in children and adolescents after the COVID-19 pandemic, United States 2018\u20132024","volume":"73","author":"Edens","year":"2024","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanmic.2024.101019","article-title":"Global spatiotemporal dynamics of Mycoplasma pneumoniae re-emergence after COVID-19 pandemic restrictions: an epidemiological and transmission modelling study","volume":"6","year":"2025","journal-title":"Lancet Microbe"},{"key":"B9","doi-asserted-by":"publisher","first-page":"e192","DOI":"10.1017\/S0950268819000839","article-title":"The epidemiology of pediatric Mycoplasma pneumoniae pneumonia in North China: 2006 to 2016","volume":"147","author":"Gao","year":"2019","journal-title":"Epidemiol. Infect."},{"key":"B10","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1007\/s00203-020-02041-4","article-title":"The mechanisms underlying antigenic variation and maintenance of genomic integrity in Mycoplasma pneumoniae and Mycoplasma genitalium","volume":"203","author":"Hakim","year":"2021","journal-title":"Arch. Microbiol."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2024.1478087","article-title":"Increased in vitro antimicrobial resistance of Mycoplasma pneumoniae isolates obtained from children in Beijing, China, in 2023","volume":"14","author":"Jia","year":"2024","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens10020119","article-title":"Mycoplasma pneumoniae infections: pathogenesis and vaccine development","volume":"10","author":"Jiang","year":"2021","journal-title":"Pathogens"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanwpc.2025.101578","article-title":"Genetic factors driving the Mycoplasma pneumoniae outbreak among children post-COVID-19 in China: a whole-genome analysis","volume":"59","author":"Jiao","year":"2025","journal-title":"Lancet Reg. Health West Pac."},{"key":"B14","doi-asserted-by":"publisher","first-page":"6724","DOI":"10.1073\/pnas.0510644103","article-title":"ADP-ribosylating and vacuolating cytotoxin of Mycoplasma pneumoniae represents a unique virulence determinant among bacterial pathogens","volume":"103","author":"Kannan","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B15","doi-asserted-by":"publisher","first-page":"4557","DOI":"10.1128\/IAI.67.9.4557-4562.1999","article-title":"Identification of a new variable sequence in the P1 cytadhesin gene of Mycoplasma pneumoniae: evidence for the generation of antigenic variation by DNA recombination between repetitive sequences","volume":"67","author":"Kenri","year":"1999","journal-title":"Infect. Immun."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1202357","article-title":"Genotyping of Mycoplasma pneumoniae strains isolated in Japan during 2019 and 2020: spread of p1 gene type 2c and 2j variant strains","volume":"14","author":"Kenri","year":"2023","journal-title":"Front. Microbiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e00026","DOI":"10.1128\/spectrum.00026-22","article-title":"Mycoplasma pneumoniae and adenovirus coinfection cause pediatric severe community-acquired pneumonia","volume":"10","author":"Li","year":"2022","journal-title":"Microbiol. Spectr."},{"key":"B18","doi-asserted-by":"publisher","first-page":"e515","DOI":"10.1016\/S2666-5247(23)00405-6","article-title":"Resurgence of Mycoplasma pneumoniae by macrolide-resistant epidemic clones in China","volume":"5","author":"Li","year":"2024","journal-title":"Lancet Microbe"},{"key":"B19","doi-asserted-by":"publisher","first-page":"343","DOI":"10.3967\/bes2017.045","article-title":"Whole Genome Analysis Reveals New Insights into Macrolide Resistance in Mycoplasma pneumoniae","volume":"30","author":"Li","year":"2017","journal-title":"BioMed. Environ. Sci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"e0137354","DOI":"10.1371\/journal.pone.0137354","article-title":"Comparative \u201c-omics\u201d in Mycoplasma pneumoniae clinical isolates reveals key virulence factors","volume":"10","author":"Lluch-Senar","year":"2015","journal-title":"PloS One"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.2807\/1560-7917.ES.2022.27.19.2100746","article-title":"Mycoplasma pneumoniae detections before and during the COVID-19 pandemic: results of a global survey 2017 to 2021","volume":"27","author":"Meyer Sauteur","year":"2022","journal-title":"Euro Surveill."},{"key":"B22","doi-asserted-by":"publisher","first-page":"6","DOI":"10.3760\/cma.j.issn.1674-2397.2019.01.002","article-title":"Guidelines for the diagnosis and treatment of community-acquired pneumonia in children (2019 version)","volume":"12","year":"2019","journal-title":"Chin. J. Clin. Infect. Dis."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1128\/JB.181.4.1079-1087.1999","article-title":"Mycoplasma pneumoniae protein P30 is required for cytadherence and associated with proper cell development","volume":"181","author":"Romero-Arroyo","year":"1999","journal-title":"J. Bacteriol."},{"key":"B24","first-page":"15666","article-title":"Effects of bacterial and viral co-infections of Mycoplasma pneumoniae pneumonia in children: analysis report from Beijing Children\u2019s Hospital between 2010 and 2014","volume":"8","author":"Song","year":"2015","journal-title":"Int. J. Clin. Exp. Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"2182","DOI":"10.1099\/mic.0.028506-0","article-title":"Sequence variations in RepMP2\/3 and RepMP4 elements reveal intragenomic homologous DNA recombination events in Mycoplasma pneumoniae","volume":"155","author":"Spuesens","year":"2009","journal-title":"Microbiol. (Reading)"},{"key":"B26","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1186\/s12864-025-12101-y","article-title":"Comparative genomic analysis of Mycoplasma pneumoniae isolated in the United Kingdom, between 2016 and 2024","volume":"26","author":"Tewolde","year":"2025","journal-title":"BMC Genomics"},{"key":"B27","doi-asserted-by":"publisher","first-page":"5188","DOI":"10.1038\/s41467-020-18777-y","article-title":"Immunodominant proteins P1 and P40\/P90 from human pathogen Mycoplasma pneumoniae","volume":"11","author":"Vizarraga","year":"2020","journal-title":"Nat. Commun."},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1186017","article-title":"Novel mechanisms of macrolide resistance revealed by in vitro selection and genome analysis in Mycoplasma pneumoniae","volume":"13","author":"Wang","year":"2023","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1007\/s12519-024-00831-0","article-title":"Expert consensus on the diagnosis and treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia in children","volume":"20","author":"Wang","year":"2024","journal-title":"World J. Pediatr."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1692","DOI":"10.3201\/eid3008.231596","article-title":"Macrolide-resistant Mycoplasma pneumoniae infections among children before and during COVID-19 pandemic, Taiwan 2017\u20132023","volume":"30","author":"Wu","year":"2024","journal-title":"Emerging Infect. Dis."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12519-023-00783-x","article-title":"Current status of Mycoplasma pneumoniae infection in China","volume":"20","author":"Yan","year":"2024","journal-title":"World J. Pediatr."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2025.40.e317","article-title":"Growing threat of macrolide-resistant Mycoplasma pneumoniae among children: what we know and what we need","volume":"40","author":"Yun","year":"2025","journal-title":"J. Korean Med. Sci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"e0141702","DOI":"10.1371\/journal.pone.0141702","article-title":"Culture-independent detection and genotyping of Mycoplasma pneumoniae in clinical specimens from Beijing, China","volume":"10","author":"Zhao","year":"2015","journal-title":"PloS One"}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1732239\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T06:41:39Z","timestamp":1767940899000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2025.1732239\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,9]]},"references-count":33,"alternative-id":["10.3389\/fcimb.2025.1732239"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2025.1732239","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,9]]},"article-number":"1732239"}}