{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:51:45Z","timestamp":1790790705103,"version":"4.1.0"},"reference-count":46,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T00:00:00Z","timestamp":1678320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Streptococcus agalactiae or group B streptococcus (GBS) is a leading cause of neonatal sepsis and increasingly found as an invasive pathogen in older patient populations. Beta-lactam antibiotics remain the most effective therapeutic with resistance rarely reported, while the majority of GBS isolates carry the tetracycline resistance gene tet(M) in fixed genomic positions amongst five predominant clonal clades. In the UK, GBS resistance to clindamycin and erythromycin has increased from 3% in 1991 to 11.9% (clindamycin) and 20.2% (erythromycin), as reported in this study. Here, a systematic investigation of antimicrobial resistance genomic content sought to fully characterise the associated mobile genetic elements within phenotypically resistant GBS isolates from 193 invasive and non-invasive infections of UK adult patients collected during 2014 and 2015. Resistance to erythromycin and clindamycin was mediated by erm(A) (16\/193, 8.2%), erm(B) (16\/193, 8.2%), mef(A)\/msr(D) (10\/193, 5.1%), lsa(C) (3\/193, 1.5%), lnu(C) (1\/193, 0.5%), and erm(T) (1\/193, 0.5%) genes. The integrative conjugative elements (ICEs) carrying these genes were occasionally found in combination with high gentamicin resistance mediating genes aac(6\u2032)-aph(2\u2033), aminoglycoside resistance genes (ant(6-Ia), aph(3\u2032-III), and\/or aad(E)), alternative tetracycline resistance genes (tet(O) and tet(S)), and\/or chloramphenicol resistance gene cat(Q), mediating resistance to multiple classes of antibiotics. This study provides evidence of the retention of previously reported ICESag37 (n = 4), ICESag236 (n = 2), and ICESpy009 (n = 3), as well as the definition of sixteen novel ICEs and three novel transposons within the GBS lineage, with no evidence of horizontal transfer.<\/jats:p>","DOI":"10.3390\/antibiotics12030544","type":"journal-article","created":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T02:33:16Z","timestamp":1678329196000},"page":"544","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Genomic Analysis Reveals New Integrative Conjugal Elements and Transposons in GBS Conferring Antimicrobial Resistance"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2266-1593","authenticated-orcid":false,"given":"Uzma Basit","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, Division of Infection and Immunity, Cardiff University, 6th Floor University Hospital of Wales, Cardiff CF14 4XN, UK"},{"name":"Parasites and Microbes Programme, The Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2142-3443","authenticated-orcid":false,"given":"Edward A. R.","family":"Portal","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Division of Infection and Immunity, Cardiff University, 6th Floor University Hospital of Wales, Cardiff CF14 4XN, UK"},{"name":"Bacterial Reference Department, UK Health Security Agency, London NW9 5DF, UK"},{"name":"Department of Biology, Ineos Oxford Institute, University of Oxford, Oxford OX1 3RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsty","family":"Sands","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Division of Infection and Immunity, Cardiff University, 6th Floor University Hospital of Wales, Cardiff CF14 4XN, UK"},{"name":"Department of Biology, Ineos Oxford Institute, University of Oxford, Oxford OX1 3RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Lo","sequence":"additional","affiliation":[{"name":"Parasites and Microbes Programme, The Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria J.","family":"Chalker","sequence":"additional","affiliation":[{"name":"Bacterial Reference Department, UK Health Security Agency, London NW9 5DF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7075-6896","authenticated-orcid":false,"given":"Elita","family":"Jauneikaite","sequence":"additional","affiliation":[{"name":"NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Department of Infectious Disease, Imperial College London, London W12 0NN, UK"},{"name":"Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London W2 1PG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9117-6911","authenticated-orcid":false,"given":"Owen B.","family":"Spiller","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Division of Infection and Immunity, Cardiff University, 6th Floor University Hospital of Wales, Cardiff CF14 4XN, UK"},{"name":"Bacterial Reference Department, UK Health Security Agency, London NW9 5DF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Navarro-Torn\u00e9, A., Curcio, D., Mo\u00efsi, J.C., and Jodar, L. (2021). Burden of invasive group B Streptococcus disease in non-pregnant adults: A systematic review and meta-analysis. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0258030"},{"key":"ref_2","first-page":"1","article-title":"Laboratory surveillance of pyogenic and non-pyogenic streptococcal bacteraemia in England (2020)","volume":"15","author":"Rudman","year":"2020","journal-title":"Health Prot. Rep."},{"key":"ref_3","unstructured":"Healy, B. (2022, December 03). Public H.W. Group B Streptococcal Infection. Available online: https:\/\/bestpractice.bmj.com\/topics\/en-gb\/924."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1080\/1040841X.2020.1758626","article-title":"A review of antibiotic resistance in Group B Streptococcus: The story so far","volume":"46","author":"Hayes","year":"2020","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_5","unstructured":"CLSI (2022). M100 Performance Standards for Antimicrobial Susceptibility Testing, Clinical and Laboratory Standards Institute. [32nd ed.]."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1093\/jac\/dkm390","article-title":"Invasive group B Streptococcus isolates showing reduced susceptibility to penicillin in Hong Kong","volume":"60","author":"Chu","year":"2007","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2890","DOI":"10.1128\/AAC.00185-08","article-title":"First molecular characterization of group B streptococci with reduced penicillin susceptibility","volume":"52","author":"Kimura","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1093\/jac\/dkr546","article-title":"Nosocomial spread of multidrug-resistant group B streptococci with reduced penicillin susceptibility belonging to clonal complex 1","volume":"67","author":"Nagano","year":"2012","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2725","DOI":"10.1093\/jac\/dkv203","article-title":"High isolation rate of MDR group B streptococci with reduced penicillin susceptibility in Japan","volume":"70","author":"Seki","year":"2015","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2915","DOI":"10.1128\/AAC.00461-08","article-title":"Point mutation in the group B streptococcal pbp2x gene conferring decreased susceptibility to \u03b2-lactam antibiotics","volume":"52","author":"Dahesh","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"574.e7","DOI":"10.1016\/j.cmi.2017.02.021","article-title":"Short-read whole genome sequencing for determination of antimicrobial resistance mechanisms and capsular serotypes of current invasive Streptococcus agalactiae recovered in the USA","volume":"23","author":"Metcalf","year":"2017","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1001\/jamainternmed.2018.7269","article-title":"Epidemiology of Invasive Group B Streptococcal Infections among Nonpregnant Adults in the United States, 2008\u20132016","volume":"179","author":"McGee","year":"2019","journal-title":"JAMA Intern. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1093\/jac\/dkp458","article-title":"Prosthetic hip joint infection with a Streptococcus agalactiae isolate not susceptible to penicillin G and ceftriaxone","volume":"65","author":"Gaudreau","year":"2009","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2983","DOI":"10.1128\/AAC.01243-10","article-title":"Novel mutations in a patient isolate of Streptococcus agalactiae with reduced penicillin susceptibility emerging after long-term oral suppressive therapy","volume":"55","author":"Longtin","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Siga\u00faque, B., Kobayashi, M., Vubil, D., Nhacolo, A., Cha\u00faque, A., Moaine, B., Massora, S., Mandomando, I., Nhampossa, T., and Bassat, Q. (2018). Invasive bacterial disease trends and characterization of group B streptococcal isolates among young infants in southern Mozambique, 2001\u20132015. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0191193"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1093\/cid\/cit337","article-title":"Emerging trends in the epidemiology of invasive group B streptococcal disease in England and Wales, 1991\u20132010","volume":"57","author":"Lamagni","year":"2013","journal-title":"Clin. Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1128\/AAC.00781-08","article-title":"Genetic elements responsible for erythromycin resistance in streptococci","volume":"53","author":"Varaldo","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1128\/AAC.01068-10","article-title":"Cross-resistance to lincosamides, streptogramins A, and pleuromutilins due to the lsa(C) Gene in Streptococcus agalactiae UCN70","volume":"55","author":"Malbruny","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1093\/jac\/dkx077","article-title":"Cross-resistance to lincosamides, streptogramins A and pleuromutilins in Streptococcus agalactiae isolates from the USA","volume":"72","author":"Hawkins","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.3389\/fmicb.2017.01921","article-title":"ICESag37, a novel integrative and conjugative element carrying antimicrobial resistance genes and potential virulence factors in Streptococcus agalactiae","volume":"8","author":"Zhou","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4544","DOI":"10.1038\/ncomms5544","article-title":"Streptococcus agalactiae clones infecting humans were selected and fixed through the extensive use of tetracycline","volume":"5","author":"Cunha","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6913","DOI":"10.1128\/JB.00824-08","article-title":"Integrative conjugative elements and related elements are major contributors to the genome diversity of Streptococcus agalactiae","volume":"190","author":"Brochet","year":"2008","journal-title":"J. Bacteriol."},{"key":"ref_23","first-page":"1483","article-title":"New Insights into the Classification and Integration Specificity of Streptococcus Integrative Conjugative Elements through Extensive Genome Exploration","volume":"6","author":"Ambroset","year":"2015","journal-title":"Front. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1093\/jac\/dkw367","article-title":"A new mosaic integrative and conjugative element from Streptococcus agalactiae carrying resistance genes for chloramphenicol (cat(Q)) and macrolides [mef(I) and erm(TR)]","volume":"72","author":"Morici","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3906","DOI":"10.1128\/AAC.03082-15","article-title":"De ICE Spy 009, a Conjugative Genetic Element Carrying mef (E) in Streptococcus pyogenes","volume":"60","author":"Grosso","year":"2012","journal-title":"Antimicrob. Agents Chemother"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2716","DOI":"10.1128\/AAC.49.7.2716-2719.2005","article-title":"New lnu (C) gene conferring resistance to lincomycin by nucleotidylation in Streptococcus agalactiae UCN36","volume":"49","author":"Achard","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_27","first-page":"3205","article-title":"Host specificity in the diversity and transfer of lsa resistance genes in group B Streptococcus","volume":"70","author":"Douarre","year":"2015","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4258","DOI":"10.1128\/AAC.00596-08","article-title":"Genetic heterogeneity in pbp genes among clinically isolated group B streptococci with reduced penicillin susceptibility","volume":"52","author":"Nagano","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"356","DOI":"10.3389\/fpubh.2018.00356","article-title":"Group B Streptococcus serotypes in pregnant women from the Western Cape region of South Africa","volume":"6","author":"Africa","year":"2018","journal-title":"Front. Public Health"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"414","DOI":"10.3343\/alm.2019.39.4.414","article-title":"First case in Korea of group B Streptococcus with reduced penicillin susceptibility harboring amino acid substitutions in penicillin-binding protein 2x","volume":"39","author":"Yi","year":"2019","journal-title":"Ann. Lab. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1128\/AAC.34.6.985","article-title":"High-level chromosomal gentamicin resistance in Streptococcus agalactiae (Group B)","volume":"34","author":"Horaud","year":"1990","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4570","DOI":"10.1128\/AAC.00521-13","article-title":"Characterization of Tn5801.Sag, a variant of Staphylococcus aureus Tn916 family transposon Tn5801 that is widespread in clinical isolates of Streptococcus agalactiae","volume":"57","author":"Mingoia","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"20047","DOI":"10.1038\/srep20047","article-title":"Clonal Complex 17 Group B Streptococcus strains causing invasive disease in neonates and adults originate from the same genetic pool","volume":"6","author":"Teatero","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"609526","DOI":"10.3389\/fmicb.2020.609526","article-title":"Predominance of III\/ST19 and Ib\/ST10 Lineages with High Multidrug Resistance in Fluoroquinolone-Resistant Group B Streptococci Isolates in Which a New Integrative and Conjugative Element Was Identified","volume":"11","author":"Gao","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2659","DOI":"10.1128\/JCM.41.6.2659-2661.2003","article-title":"Molecular epidemiology of macrolide resistance in neonatal bloodstream isolates of group B streptococci","volume":"41","author":"Diekema","year":"2003","journal-title":"J. Clin. Microbiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2166","DOI":"10.1128\/JCM.41.5.2166-2169.2003","article-title":"A serotype V clone is predominant among erythromycin-resistant Streptococcus agalactiae isolates in a southwestern region of Germ(A)ny","volume":"41","author":"Ruess","year":"2003","journal-title":"J. Clin. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"264","DOI":"10.3389\/fmicb.2019.00264","article-title":"Molecular characteristics and antimicrobial resistance of group B Streptococcus strains causing invasive disease in neonates and adults","volume":"10","author":"Tsai","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1700473","DOI":"10.2807\/1560-7917.ES.2018.23.21.1700473","article-title":"Increasing macrolide resistance among Streptococcus agalactiae causing invasive disease in non-pregnant adults was driven by a single capsular-transformed lineage, Portugal, 2009 to 2015","volume":"23","author":"Lopes","year":"2018","journal-title":"Eurosurveillance"},{"key":"ref_39","first-page":"000783","article-title":"Identifying large-scale recombination and capsular switching events in Streptococcus agalactiae strains causing disease in adults in the UK between 2014 and 2015","volume":"8","author":"Khan","year":"2022","journal-title":"Microb. Genom."},{"key":"ref_40","first-page":"Doc18","article-title":"Survey of strain distribution and antibiotic resistance pattern of group B streptococci (Streptococcus agalactiae) isolated from clinical specimens","volume":"11","author":"Mousavi","year":"2016","journal-title":"GMS Hyg. Infect. Control"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1038\/s41564-021-00870-7","article-title":"Characterization of antimicrobial-resistant Gram-negative bacteria that cause neonatal sepsis in seven low- and middle-income countries","volume":"6","author":"Sands","year":"2021","journal-title":"Nat. Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Wick, R.R., Judd, L.M., Gorrie, C.L., and Holt, K.E. (2017). Unicycler: Resolving bacterial genome assemblies from short and long sequencing reads. PLoS Comput. Biol., 13.","DOI":"10.1371\/journal.pcbi.1005595"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3350","DOI":"10.1093\/bioinformatics\/btv383","article-title":"Bandage: Interactive visualization of de novo genome assemblies","volume":"31","author":"Wick","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s13100-019-0182-3","article-title":"The Transposon Registry","volume":"10","author":"Tansirichaiya","year":"2019","journal-title":"Mob. DNA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1093\/jac\/dks496","article-title":"Genotyping using whole-genome sequencing is a realistic alternative to surveillance based on phenotypic antimicrobial susceptibility testing","volume":"68","author":"Zankari","year":"2013","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1093\/bioinformatics\/btr703","article-title":"Artemis: An integrated platform for visualization and analysis of high-throughput sequence-based experimental data","volume":"28","author":"Carver","year":"2012","journal-title":"Bioinformatics"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/12\/3\/544\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:51:30Z","timestamp":1760122290000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/12\/3\/544"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,9]]},"references-count":46,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["antibiotics12030544"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics12030544","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,9]]}}}