{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T07:42:53Z","timestamp":1776411773672,"version":"3.51.2"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":13,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The macrolide resistance in Bordetella pertussis cannot be fully explained by 23S rRNA mutations, underscoring the need for comprehensive methods to detect resistant isolates and clarify mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Whole-genome sequencing data from 556 isolates with macrolide resistance information, including 398 resistant and 158 sensitive strains, were retrieved from the National Center for Biotechnology Information (NCBI). A k-mer-based genome-wide k-mer-based association studies using Pyseer identified 1322 resistance-associated k-mers. Refinement with Scoary2, least absolute shrinkage and selection operator (LASSO) and variable selection using random forests (VSURF) yielded six key k-mers, enabling the construction of a simplified model for predicting resistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 1322 different k-mers were involved in resistance. In the further simplified model, only six k-mers were included, in which a DHCW motif cupin fold protein (odds ratio [OR]: 25.84, 95% confidence interval [CI]: 15.58\u201344.03) and an IS481 insertion sequence located near infA (OR: 28.96, 95% CI: 7.64\u2013243.86) showed strong associations with resistance. Despite the reduced feature set, the simplified model achieved classification performance comparable to the initial model, with similar sensitivity (97.7% versus 98.7%), specificity (92.1% versus 99.5%), and accuracy (93.4% versus 99.3%). Notably, it maintained a robust area under the receiver operating characteristic curve (area under the curve = 0.98), indicating strong predictive capability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study developed a simplified k-mer-based model for accurately identifying macrolide-resistant B. pertussis isolates and uncovered novel resistance features.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jac\/dkag131","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T11:44:50Z","timestamp":1775216690000},"source":"Crossref","is-referenced-by-count":0,"title":["Genome-wide association studies builds a predictive model and reveals novel resistance features for macrolide-resistant\n                    <i>Bordetella pertussis<\/i>"],"prefix":"10.1093","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-8005-960X","authenticated-orcid":false,"given":"Jialiang","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, Aerospace Center Hospital , Beijing 100049 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guowei","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Aerospace Center Hospital , Beijing 100049 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"2026041702462515300_dkag131-B1","doi-asserted-by":"publisher","first-page":"Cd004404","DOI":"10.1002\/14651858.CD004404.pub3","article-title":"Antibiotics for whooping cough (pertussis)","volume":"2007","author":"Altunaiji","year":"2007","journal-title":"Cochrane Database Syst Rev"},{"key":"2026041702462515300_dkag131-B2","doi-asserted-by":"publisher","first-page":"mtsi.v3i4.2023.446","DOI":"10.48327\/mtsi.v3i4.2023.446","article-title":"[Pertussis worldwide. Vaccinating children and adults]","volume":"3","author":"Gendrel","year":"2023","journal-title":"Med Trop Sante Int"},{"key":"2026041702462515300_dkag131-B3"},{"key":"2026041702462515300_dkag131-B4","doi-asserted-by":"publisher","first-page":"106289","DOI":"10.1016\/j.jinf.2024.106289","article-title":"Global resurgence of pertussis: a perspective from China","volume":"89","author":"Liu","year":"2024","journal-title":"J Infect"},{"key":"2026041702462515300_dkag131-B5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jinf.2019.04.011","article-title":"Increased susceptibility to pertussis in adults at childbearing age as determined by comparative seroprevalence study, China 2010-2016","volume":"79","author":"Zhang","year":"2019","journal-title":"J Infect"},{"key":"2026041702462515300_dkag131-B6"},{"key":"2026041702462515300_dkag131-B7","doi-asserted-by":"publisher","first-page":"106835","DOI":"10.1016\/j.ijantimicag.2023.106835","article-title":"Domination of an emerging erythromycin-resistant ptxP3 Bordetella pertussis clone in Shanghai, China","volume":"62","author":"Cai","year":"2023","journal-title":"Int J Antimicrob Agents"},{"key":"2026041702462515300_dkag131-B8","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.3390\/antibiotics11111570","article-title":"Macrolide resistance in Bordetella pertussis: current situation and future challenges","volume":"11","author":"Ivaska","year":"2022","journal-title":"Antibiotics (Basel)"},{"key":"2026041702462515300_dkag131-B9","doi-asserted-by":"publisher","first-page":"2205","DOI":"10.3201\/eid2512.181836","article-title":"High prevalence of macrolide-resistant Bordetella pertussis and ptxP1 genotype, Mainland China, 2014-2016","volume":"25","author":"Li","year":"2019","journal-title":"Emerg Infect Dis"},{"key":"2026041702462515300_dkag131-B10","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1080\/22221751.2019.1587315","article-title":"Genomic epidemiology of erythromycin-resistant Bordetella pertussis in China","volume":"8","author":"Xu","year":"2019","journal-title":"Emerg Microbes Infect"},{"key":"2026041702462515300_dkag131-B11","doi-asserted-by":"publisher","first-page":"e18190","DOI":"10.5812\/jjm.8(5)2015.18190","article-title":"Isolation of high level macrolide resistant Bordetella pertussis without transition mutation at domain V in Iran","volume":"8","author":"Mirzaei","year":"2015","journal-title":"Jundishapur J Microbiol"},{"key":"2026041702462515300_dkag131-B12","doi-asserted-by":"publisher","first-page":"e0138941","DOI":"10.1371\/journal.pone.0138941","article-title":"Variation in Bordetella pertussis susceptibility to erythromycin and virulence-related genotype changes in China (1970-2014)","volume":"10","author":"Yang","year":"2015","journal-title":"PLoS One"},{"key":"2026041702462515300_dkag131-B13","doi-asserted-by":"publisher","first-page":"e0049324","DOI":"10.1128\/spectrum.00493-24","article-title":"Genome-based model for differentiating between infection and carriage Staphylococcus aureus","volume":"12","author":"Chen","year":"2024","journal-title":"Microbiol Spectr"},{"key":"2026041702462515300_dkag131-B14","doi-asserted-by":"publisher","first-page":"39","DOI":"10.3201\/eid3001.221927","article-title":"Disease-associated Streptococcus pneumoniae genetic variation","volume":"30","author":"Yang","year":"2024","journal-title":"Emerg Infect Dis"},{"key":"2026041702462515300_dkag131-B15","doi-asserted-by":"publisher","first-page":"1428766","DOI":"10.3389\/fmicb.2024.1428766","article-title":"Molecular epidemiology and genomic features of Bordetella parapertussis in Shanghai, China, 2017-2022","volume":"15","author":"Fu","year":"2024","journal-title":"Front Microbiol"},{"key":"2026041702462515300_dkag131-B16","doi-asserted-by":"publisher","first-page":"1498638","DOI":"10.3389\/fmicb.2024.1498638","article-title":"Molecular characterization and antimicrobial susceptibility for 62 isolates of Bordetella pertussis from children","volume":"15","author":"He","year":"2024","journal-title":"Front Microbiol"},{"key":"2026041702462515300_dkag131-B17","doi-asserted-by":"publisher","first-page":"901617","DOI":"10.3389\/fmicb.2022.901617","article-title":"A cross-sectional study revealing the emergence of erythromycin-resistant Bordetella pertussis carrying ptxP3 alleles in China","volume":"13","author":"Wu","year":"2022","journal-title":"Front Microbiol"},{"key":"2026041702462515300_dkag131-B18","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1080\/14760584.2020.1831916","article-title":"The epidemic of erythromycin-resistant Bordetella pertussis with limited genome variation associated with pertussis resurgence in China","volume":"19","author":"Yao","year":"2020","journal-title":"Expert Rev Vaccines"},{"key":"2026041702462515300_dkag131-B19","doi-asserted-by":"publisher","first-page":"e0243221","DOI":"10.1128\/aac.02432-21","article-title":"Macrolide resistance in Mycoplasma pneumoniae, Midwestern United States, 2014 to 2021","volume":"66","author":"Rothstein","year":"2022","journal-title":"Antimicrob Agents Chemother"},{"key":"2026041702462515300_dkag131-B20","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1007\/s12519-019-00308-5","article-title":"Clinical characteristics, molecular epidemiology and antimicrobial susceptibility of pertussis among children in southern China","volume":"16","author":"Zhang","year":"2020","journal-title":"World J Pediatr"},{"key":"2026041702462515300_dkag131-B21","doi-asserted-by":"publisher","first-page":"3000605221078782","DOI":"10.1177\/03000605221078782","article-title":"Macrolide susceptibility and molecular characteristics of Bordetella pertussis","volume":"50","author":"Zhang","year":"2022","journal-title":"J Int Med Res"},{"key":"2026041702462515300_dkag131-B22","doi-asserted-by":"publisher","first-page":"102610","DOI":"10.1016\/j.jiph.2024.102610","article-title":"Pertussis clinical profile shift, severity, prediction in a tertiary hospital: a comparative study before, during, and after COVID-19 in Southern China","volume":"18","author":"Tian","year":"2025","journal-title":"J Infect Public Health"},{"key":"2026041702462515300_dkag131-B23","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/j.ijid.2023.01.005","article-title":"Emergence and spread of MT28 ptxP3 allele macrolide-resistant Bordetella pertussis from 2021 to 2022 in China","volume":"128","author":"Fu","year":"2023","journal-title":"Int J Infect Dis"},{"key":"2026041702462515300_dkag131-B24","doi-asserted-by":"publisher","first-page":"113","DOI":"10.3760\/cma.j.cn112137-20240805-01797","article-title":"[Issues and recommendations on antibacterial treatment and post-exposure chemoprophylaxis for pertussis]","volume":"105","author":"Zeng","year":"2025","journal-title":"Zhonghua Yi Xue Za Zhi"},{"key":"2026041702462515300_dkag131-B25","doi-asserted-by":"publisher","first-page":"100098","DOI":"10.1016\/j.lanwpc.2021.100098","article-title":"Emerging macrolide resistance in Bordetella pertussis in mainland China: findings and warning from the global pertussis initiative","volume":"8","author":"Feng","year":"2021","journal-title":"Lancet Reg Health West Pac"},{"key":"2026041702462515300_dkag131-B26","doi-asserted-by":"publisher","first-page":"e301","DOI":"10.1093\/infdis\/jiaf208","article-title":"Impact of macrolide resistance on azithromycin for prevention of rehospitalization or death among children discharged from hospitals in Western Kenya","volume":"232","author":"Mogeni","year":"2025","journal-title":"J Infect Dis"},{"key":"2026041702462515300_dkag131-B27","doi-asserted-by":"publisher","first-page":"2034","DOI":"10.1016\/j.meegid.2011.09.012","article-title":"Differences in the genomic content of Bordetella pertussis isolates before and after introduction of pertussis vaccines in four European countries","volume":"11","author":"Kallonen","year":"2011","journal-title":"Infect Genet Evol"},{"key":"2026041702462515300_dkag131-B28","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.13345\/j.cjb.180187","article-title":"Progress in regulatory mechanism for inducing \u03b2-lactamase in Gram-negative bacteria","volume":"34","author":"Xu","year":"2018","journal-title":"Sheng Wu Gong Cheng Xue Bao"},{"key":"2026041702462515300_dkag131-B29","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/s11274-020-02862-x","article-title":"Transcriptional regulation of drug resistance mechanisms in Salmonella: where we stand and what we need to know","volume":"36","author":"Shaheen","year":"2020","journal-title":"World J Microbiol Biotechnol"},{"key":"2026041702462515300_dkag131-B30","doi-asserted-by":"publisher","first-page":"1661","DOI":"10.1080\/21505594.2021.1936767","article-title":"Yhjc is a novel transcriptional regulator required for Shigella flexneri virulence","volume":"12","author":"Li","year":"2021","journal-title":"Virulence"},{"key":"2026041702462515300_dkag131-B31","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1080\/22221751.2019.1601502","article-title":"The evolution of Bordetella pertussis has selected for mutations of acr that lead to sensitivity to hydrophobic molecules and fatty acids","volume":"8","author":"MacArthur","year":"2019","journal-title":"Emerg Microbes Infect"},{"key":"2026041702462515300_dkag131-B32","doi-asserted-by":"publisher","first-page":"2505","DOI":"10.1128\/AEM.07651-11","article-title":"Ring-cleaving dioxygenases with a cupin fold","volume":"78","author":"Fetzner","year":"2012","journal-title":"Appl Environ Microbiol"},{"key":"2026041702462515300_dkag131-B33","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1007\/s11274-023-03870-3","article-title":"An oxalate decarboxylase-like cupin domain containing protein is involved in imparting acid stress tolerance in Bacillus amyloliquefaciens MBNC","volume":"40","author":"Chowdhury","year":"2024","journal-title":"World J Microbiol Biotechnol"},{"key":"2026041702462515300_dkag131-B34","doi-asserted-by":"publisher","first-page":"e0221024","DOI":"10.1128\/spectrum.02210-24","article-title":"Do not let perfect be the enemy of good: the current reality of Bordetella testing","volume":"13","author":"Yee","year":"2025","journal-title":"Microbiol Spectr"},{"key":"2026041702462515300_dkag131-B35","doi-asserted-by":"publisher","first-page":"6034","DOI":"10.1016\/j.vaccine.2009.07.074","article-title":"First report and detailed characterization of B. pertussis isolates not expressing pertussis toxin or pertactin","volume":"27","author":"Bouchez","year":"2009","journal-title":"Vaccine"},{"key":"2026041702462515300_dkag131-B36","doi-asserted-by":"publisher","first-page":"e17797","DOI":"10.1371\/journal.pone.0017797","article-title":"Differential expression of type III effector BteA protein due to IS481 insertion in Bordetella pertussis","volume":"6","author":"Han","year":"2011","journal-title":"PLoS One"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/81\/5\/dkag131\/68089991\/dkag131.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jac\/article-pdf\/81\/5\/dkag131\/68089991\/dkag131.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T06:46:36Z","timestamp":1776408396000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/doi\/10.1093\/jac\/dkag131\/8654734"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,3]]},"references-count":36,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,4,3]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkag131","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,5]]},"published":{"date-parts":[[2026,4,3]]},"article-number":"dkag131"}}