{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T06:18:07Z","timestamp":1787897887169,"version":"build-2784847793"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"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. Public Health"],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Reduced susceptibility to penicillin in\n                      <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n                      is mediated primarily by alterations in penicillin-binding proteins (PBPs) and often coexists with multidrug resistance within successful lineages. The region-specific genomic characterization of clinically relevant pneumococci with reduced penicillin susceptibility in Southwest China remains limited.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed whole-genome sequencing of 204 clinical\n                      <jats:italic>S. pneumoniae<\/jats:italic>\n                      isolates collected from five institutions in Southwest China (2018\u20132022) that met our operational screening definition of reduced susceptibility to penicillin (PEN MIC \u22650.12\u202f\u03bcg\/mL). Molecular serotypes, MLST types, and Global Pneumococcal Sequence Clusters (GPSCs) were assigned; virulence and antimicrobial resistance determinants were profiled; and a core genome phylogeny was reconstructed with international contextualization through the use of PubMLST genomes meeting the same MIC criterion. Amino acid variability in PBP1a\/PBP2b\/PBP2x was quantified using TIGR4 numbering, and highly variable noncatalytic residues located within 15\u202f\u00c5 of catalytic motifs were prioritized via structure-guided screening.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The isolates showed a high burden of resistance to non-\u03b2-lactam antibiotics (erythromycin, 98.5%; tetracycline, 82.8%; trimethoprim\u2013sulfamethoxazole, 64.7%), while fluoroquinolone susceptibility was largely preserved (\u226597%), and vancomycin\/linezolid resistance was not detected. Twenty-seven serotypes were identified, among which 19F (23.5%) and 19A (14.2%) were dominant, and the estimated PCV13 coverage was 69.6%. GPSC1 was the dominant lineage (36.8%), and the lineage composition among our isolates differed markedly from those in the PubMLST-USA and PubMLST-Thailand subsets. Virulence and resistance gene carriage differed markedly between GPSC1 and non-GPSC1 isolates, with enrichment of pilus operons,\n                      <jats:italic>mef(A)\/msr(D)<\/jats:italic>\n                      , and\n                      <jats:italic>folA\/folP<\/jats:italic>\n                      in GPSC1. PBP variations were clustered in transpeptidase domains and motif-adjacent regions while essential catalytic residues were conserved; with the structure-guided filter, 12, 11, and 11 motif-proximal noncatalytic candidate sites were prioritized in PBP1a, PBP2b, and PBP2x, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Clinical\n                      <jats:italic>S. pneumoniae<\/jats:italic>\n                      isolates with reduced penicillin susceptibility collected in Southwest China demonstrated resistance and accessory gene profiles that were strongly structured by a GPSC-defined lineage background. Our site-resolved, structure-guided PBP analysis provides a regional PBP variability landscape and a compact set of recurrent motif-proximal candidate substitutions to support surveillance and downstream functional validation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fpubh.2026.1844601","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T05:36:02Z","timestamp":1787895362000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Lineage structure and penicillin-binding protein variability in clinical Streptococcus pneumoniae isolates from Southwest China exhibiting reduced susceptibility to penicillin"],"prefix":"10.3389","volume":"14","author":[{"given":"Chenglin","family":"Miao","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, West China Second University Hospital, Sichuan University","place":["Chengdu, 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Hospital","place":["Nanchong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, West China Second University Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"School of Medical Technology, Chengdu University of Traditional Chinese Medicine","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, West China Second University Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linghan","family":"Kuang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, West China Second University Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Department of Laboratory Medicine, Chengdu Hi-Tech Zone Hospital for Women and Children (Chengdu Hi-Tech Zone Hospital for Maternal and Child Healthcare)","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingxin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, West China Second University Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaji","family":"Ling","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, West China Second University Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, West China Second University Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huilian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, West China Second University Hospital (Tianfu), Sichuan University (Sichuan Provincial Children's Hospital)","place":["Meishan, China"]},{"name":"Department of Laboratory Medicine, Meishan Women and Children\u2019s Hospital","place":["Meishan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaocui","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Chengdu Jinjiang District Maternal and Child Healthcare Hospital","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinghua","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, The First People\u2019s Hospital of Longquanyi District","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yali","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, West China Second University Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Department of Laboratory Medicine, West China Second University Hospital (Tianfu), Sichuan University (Sichuan Provincial Children's Hospital)","place":["Meishan, China"]},{"name":"Department of Laboratory Medicine, Meishan Women and Children\u2019s Hospital","place":["Meishan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Clinical Laboratory Medicine Research Center, West China Hospital, Sichuan University (Sichuan Clinical Research Center for Laboratory Medicine)","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongmei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, West China Second University Hospital, Sichuan University","place":["Chengdu, China"]},{"name":"Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/s41579-018-0001-8","article-title":"Streptococcus pneumoniae: transmission, colonization and invasion","volume":"16","author":"Weiser","year":"2018","journal-title":"Nat Rev Microbiol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"2221","DOI":"10.1016\/s0140-6736(22)02185-7","article-title":"Global mortality associated with 33 bacterial pathogens in 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