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PCR detection and isolation culture of\n Bartonella<\/jats:italic>\n were performed on 50 captured pikas in their habitats on the Qinghai-Tibet Plateau. The Qinghai-Tibet isolates were identified through\n gltA<\/jats:italic>\n and\n rpoB<\/jats:italic>\n phylogenetic analysis, ANI analysis, and single-copy homologous gene phylogeny. Reference genomes of\n Bartonella<\/jats:italic>\n species were analyzed for virulence classification via pan-genome and virulence factor comparisons.\n Bartonella<\/jats:italic>\n species were categorized into five virulence groups, including a high-virulence group containing\n Bartonella henselae, B. quintana, B. kosoyi, B. koehlerae<\/jats:italic>\n , and\n B. tribocorum. B. bacilliformis<\/jats:italic>\n lacked\n Trw<\/jats:italic>\n and\n VirB\/VirD4<\/jats:italic>\n , while the copy number of\n flagella<\/jats:italic>\n was significantly higher.\n Bartonella grahamii<\/jats:italic>\n infected up to 12% of plateau pikas from the Qinghai-Tibet Plateau.\n B. grahamii<\/jats:italic>\n plateau isolate had the most unique genes (5.6%), with 65.06% of them unknown in function, followed by replication, recombination, and repair (11.64%), and amino acid transport and metabolism (5.48%). The\n heme-binding protein<\/jats:italic>\n virulence factor in\n B. grahamii<\/jats:italic>\n plateau isolate exhibited 14 amino acid mutations, leading to changes in the protein-binding sites.\n Bartonella<\/jats:italic>\n can be classified into five virulence groups. In the high-virulence group, the less common\n B. tribocorum<\/jats:italic>\n and\n B. kosoyi<\/jats:italic>\n are included.\n Trw<\/jats:italic>\n and\n VirB\/VirD4<\/jats:italic>\n gradually replaced ancestral\n flagella<\/jats:italic>\n genes in\n Bartonella<\/jats:italic>\n evolution. The isolated strains have more unique genes due to plateau pikas\u2019 unique physiological traits, which may be connected to adaptation to the high-altitude host environment.\n <\/jats:p>\n \n IMPORTANCE<\/jats:title>\n \n Bartonella<\/jats:italic>\n species are emerging zoonotic pathogens capable of infecting a wide range of mammals, including humans. Understanding their virulence and evolution is critical for assessing potential public health risks. This study classifies\n Bartonella<\/jats:italic>\n species based on virulence factors, revealing species with potential human pathogenicity. The Qinghai-Tibet Plateau, with its extreme environment, may drive bacterial adaptation. By analyzing\n Bartonella<\/jats:italic>\n isolates from plateau pikas, we identified unique genes and virulence factor variations, providing insights into bacterial evolution in high-altitude hosts. Our findings highlight the significance of pan-genome analysis in identifying pathogenic traits and evaluating zoonotic risks. This study enhances our understanding of\n Bartonella<\/jats:italic>\n adaptation, aiding in the clinical identification and characterization of highly pathogenic strains.\n <\/jats:p>\n <\/jats:sec>\n <\/jats:sec>","DOI":"10.1128\/spectrum.00465-25","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T14:00:42Z","timestamp":1762869642000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Pan-genome classification of the virulence spectrum of\n Bartonella<\/i>\n and the variation of heme-binding protein virulence factor in isolates from the Tibetan Plateau"],"prefix":"10.1128","volume":"13","author":[{"given":"Jing-peng","family":"Liu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01czqbr06","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Public Health, Lanzhou University","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhou","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01czqbr06","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Public Health, Lanzhou University","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi","family":"Zhang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01czqbr06","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Public Health, Lanzhou University","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wu","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01czqbr06","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Public Health, Lanzhou University","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-juan","family":"Ma","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00qzjvm58","id-type":"ROR","asserted-by":"publisher"}],"name":"Qinghai Center for Disease Control and Prevention","place":["Xining, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5646-9295","authenticated-orcid":true,"given":"Rui","family":"Qi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01czqbr06","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Public Health, Lanzhou University","place":["Lanzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/tropicalmed4020069"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1155\/2023\/7867562"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ram.2024.04.001"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2022.106368"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jiph.2024.02.009"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13071-018-3152-6"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00056-17"},{"key":"e_1_3_5_9_2","first-page":"152","article-title":"Cat-scratch disease","volume":"83","author":"Klotz SA","year":"2011","unstructured":"Klotz SA, Ianas V, Elliott SP. 2011. 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