{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:03:35Z","timestamp":1790697815052,"version":"4.1.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"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. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Haemophilus influenzae<\/jats:italic>\n                      is an important respiratory colonizer and opportunistic pathogen. In the post-Hib vaccine era, non-type b and nontypeable strains have become increasingly associated with clinical disease, while \u03b2-lactam resistance complicates treatment and surveillance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To investigate the genetic basis and dissemination of \u03b2-lactam resistance, we performed comparative whole-genome analysis of 65 respiratory\n                      <jats:italic>H. influenzae<\/jats:italic>\n                      isolates from sputum and bronchial lavage fluid. The collection showed a highly polyclonal structure, including 28 known sequence types and 12 unassigned isolates.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Phylogenetic analysis demonstrated that \u03b2-lactamase-positive isolates were distributed across multiple lineages. Genotype-phenotype association analysis identified\n                      <jats:italic>blaTEM-1<\/jats:italic>\n                      as strongly associated with ampicillin resistance, whereas PBP3 substitutions including\n                      <jats:italic>ftsI_S357N<\/jats:italic>\n                      ,\n                      <jats:italic>ftsI_S385T<\/jats:italic>\n                      , and\n                      <jats:italic>ftsI_L389F<\/jats:italic>\n                      were significantly linked to cefuroxime resistance. Several\n                      <jats:italic>blaTEM<\/jats:italic>\n                      -negative but ampicillin-resistant isolates carried similar compound\n                      <jats:italic>ftsI<\/jats:italic>\n                      mutation profiles, indicating that \u03b2-lactam susceptibility is shaped by both enzymatic resistance and PBP3 target modification. Pangenome analysis identified 4,223 gene clusters, comprising 1,224 core, 1,913 dispensable, and 1,086 private clusters. Presence\/absence association analysis revealed that significant signals were concentrated in ampicillin resistance and formed a co-occurring dispensable-genome module containing\n                      <jats:italic>bla<\/jats:italic>\n                      ,\n                      <jats:italic>tnpA<\/jats:italic>\n                      ,\n                      <jats:italic>tnpR<\/jats:italic>\n                      , and multiple hypothetical proteins. This module mapped to a putative ICEHinR2866\/ICEHin1056-like mobile genetic region carrying\n                      <jats:italic>blaTEM-1B<\/jats:italic>\n                      , conjugation-associated components, and macrolide resistance determinants.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These findings suggest that \u03b2-lactam resistance in respiratory\n                      <jats:italic>H. influenzae<\/jats:italic>\n                      is driven by combined effects of \u03b2-lactamase production, composite PBP3 substitutions, and ICE-like mobile resistance platforms.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1945657","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:13:09Z","timestamp":1790694789000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic organization and mobile-element basis of \u03b2-lactam resistance in a polyclonal respiratory Haemophilus influenzae population"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiaomei","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University","place":["Chongqing, China"]},{"name":"Department of Infectious Diseases, Affiliated Fifth People\u2019s Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yupeng","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Technology, Affiliated Fifth People\u2019s Hospital of Chengdu University of Traditional Chinese Medicine","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juntao","family":"Tan","sequence":"additional","affiliation":[{"name":"College of Medical Informatics, Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu","place":["Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu","place":["Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dazhi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/femspd\/ftx042","article-title":"Insights on persistent airway infection by non-typeable Haemophilus influenzae in chronic obstructive pulmonary disease.","volume":"75","author":"Ahearn","year":"2017","journal-title":"Pathog. 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