{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T06:43:36Z","timestamp":1776235416788,"version":"3.50.1"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"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>Pharmaceutical cleanrooms remain vulnerable to microbial contamination introduced through environmental and personnel-associated pathways, yet the genomic characteristics and transmission dynamics of these contaminants are not well defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, whole-genome sequencing (WGS) was applied to characterize microbial populations across a sterile vaccine production line. We adopted an integrated strategy that combined routine environmental monitoring with targeted genomic investigation, mapping the overall distribution of microorganisms and prioritizing isolates showing abnormal or recurrent detection for sequencing. By integrating SNP-based phylogeny, sampling location metadata, and ARG\/virulence profiling. we identified five dominant opportunistic species, each displaying distinct genomic signatures indicative of different introduction pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      By combining species-specific genomic features with their sampling distributions, we reconstructed four plausible contamination chains: clonal inward dissemination of\n                      <jats:italic>Burkholderia contaminans<\/jats:italic>\n                      from Grade B to Grade A areas, repeated water-associated introductions of\n                      <jats:italic>Ralstonia pickettii<\/jats:italic>\n                      , intermittent personnel-mediated seeding of\n                      <jats:italic>Staphylococcus epidermidis<\/jats:italic>\n                      , and sporadic external incursions of\n                      <jats:italic>Microbacterium laevaniformans<\/jats:italic>\n                      . ARGs and VFs were heterogeneously distributed, with mobile resistance determinants and colonization- or immune-evasion factors concentrated in\n                      <jats:italic>B. contaminans<\/jats:italic>\n                      and\n                      <jats:italic>R. pickettii<\/jats:italic>\n                      , suggesting elevated persistence potential under disinfectant pressure.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings demonstrate that WGS enables precise source attribution and transmission-route reconstruction beyond the capability of conventional typing methods, thereby supporting real-time contamination control and evidence-based microbial-risk management in pharmaceutical manufacturing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1807989","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T05:42:26Z","timestamp":1776231746000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Leveraging whole-genome sequencing for microbial contamination tracking and risk assessment in pharmaceutical manufacturing"],"prefix":"10.3389","volume":"17","author":[{"given":"Qiongqiong","family":"Li","sequence":"first","affiliation":[{"name":"National Medical Products Administration Innovation Laboratory for Drug Regulatory Science, Shanghai Quality Inspection and Testing Center of Innovative Biological Products, Shanghai Institute for Drug Control","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deyin","family":"Deng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Microbiol Technology and Bioinformatics of Zhejiang Province, Zhejiang Institute of Microbiology","place":["Hangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Dou","sequence":"additional","affiliation":[{"name":"National Medical Products Administration Innovation Laboratory for Drug Regulatory Science, Shanghai Quality Inspection and Testing Center of Innovative Biological Products, Shanghai Institute for Drug Control","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinqin","family":"Chen","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Quality Inspection and Technical Research Co., Ltd.","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuhua","family":"Duan","sequence":"additional","affiliation":[{"name":"National Medical Products Administration Innovation Laboratory for Drug Regulatory Science, Shanghai Quality Inspection and Testing Center of Innovative Biological Products, Shanghai Institute for Drug Control","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingzhang","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Microbiol Technology and Bioinformatics of Zhejiang Province, Zhejiang Institute of Microbiology","place":["Hangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minghui","family":"Song","sequence":"additional","affiliation":[{"name":"National Medical Products Administration Innovation Laboratory for Drug Regulatory Science, Shanghai Quality Inspection and Testing Center of Innovative Biological Products, Shanghai Institute for Drug Control","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1038\/486465a","article-title":"Sustainable farming: get pigs off antibiotics","volume":"486","author":"Aarestrup","year":"2012","journal-title":"Nature"},{"key":"ref2","first-page":"36","article-title":"Environmental monitoring and control: proposed standards, current practices, and future directions","volume":"51","author":"Akers","year":"1997","journal-title":"PDA J. Pharm. Sci. Technol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"D690","DOI":"10.1093\/nar\/gkac920","article-title":"CARD 2023: expanded curation, support for machine learning, and resistome prediction at the comprehensive antibiotic resistance database","volume":"51","author":"Alcock","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1289\/ehp.1206316","article-title":"Human health risk assessment (HHRA) for environmental development and transfer of antibiotic resistance","volume":"121","author":"Ashbolt","year":"2013","journal-title":"Environ. Health Perspect."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"108148","DOI":"10.1016\/j.foodcont.2021.108148","article-title":"Guidance document on the use of whole genome sequencing (WGS) for source tracking from a food industry perspective","volume":"130","author":"Baert","year":"2021","journal-title":"Food Control"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.tim.2006.02.006","article-title":"Co-selection of antibiotic and metal resistance","volume":"14","author":"Baker-Austin","year":"2006","journal-title":"Trends Microbiol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"D621","DOI":"10.1093\/nar\/gkr846","article-title":"ICEberg: a web-based resource for integrative and conjugative elements found in Bacteria","volume":"40","author":"Bi","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"298","DOI":"10.3390\/microorganisms7090298","article-title":"Emergence and dissemination of mcr-carrying clinically relevant Salmonella typhimurium monophasic clone ST34","volume":"7","author":"Biswas","year":"2019","journal-title":"Microorganisms"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1774","DOI":"10.3390\/antibiotics11121774","article-title":"Whole genome sequencing (WGS) analysis of virulence and AMR genes in extended-spectrum \u03b2-lactamase (ESBL)-producing Escherichia coli from animal and environmental samples in four Italian swine farms","volume":"11","author":"Bonvegna","year":"2022","journal-title":"Antibiotics."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.ijantimicag.2012.01.011","article-title":"Emergence of resistance to antibacterial agents: the role of quaternary ammonium compounds--a critical review","volume":"39","author":"Buffet-Bataillon","year":"2012","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1111\/jam.13186","article-title":"Prevalence of Staphylococcus aureus from nares and hands on health care professionals in a Portuguese hospital","volume":"121","author":"Castro","year":"2016","journal-title":"J. Appl. Microbiol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","article-title":"Fastp: an ultra-fast all-in-one FASTQ preprocessor","volume":"34","author":"Chen","year":"2018","journal-title":"Bioinformatics"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1002\/(SICI)1099-1050(199605)5:3<217::AID-HEC200>3.0.CO;2-S","article-title":"Superbugs: should antimicrobial resistance be included as a cost in economic evaluation?","volume":"5","author":"Coast","year":"1996","journal-title":"Health Econ."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1111\/j.1365-2133.2008.08437.x","article-title":"Skin microbiota: a source of disease or defence?","volume":"158","author":"Cogen","year":"2008","journal-title":"Br. J. Dermatol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1007\/s10123-020-00151-z","article-title":"Distribution of Burkholderia cepacia complex species isolated from industrial processes and contaminated products in Argentina","volume":"24","author":"De Volder","year":"2021","journal-title":"Int. Microbiol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1146\/annurev-food-041715-033259","article-title":"Genomic epidemiology: whole-genome-sequencing-powered surveillance and outbreak investigation of foodborne bacterial pathogens","volume":"7","author":"Deng","year":"2016","journal-title":"Annu. Rev. Food Sci. Technol."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.scitotenv.2019.05.302","article-title":"Heavy metal-induced co-selection of antibiotic resistance genes in the gut microbiota of collembolans","volume":"683","author":"Ding","year":"2019","journal-title":"Sci. Total Environ."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"8084","DOI":"10.1038\/s41467-024-51864-y","article-title":"An expanded database and analytical toolkit for identifying bacterial virulence factors and their associations with chronic diseases","volume":"15","author":"Dong","year":"2024","journal-title":"Nat. Commun."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1038\/nrmicro2415","article-title":"The biofilm matrix","volume":"8","author":"Flemming","year":"2010","journal-title":"Nat. Rev. Microbiol."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1099\/ijs.0.64483-0","article-title":"DNA-DNA hybridization values and their relationship to whole-genome sequence similarities","volume":"57","author":"Goris","year":"2007","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"ref21","volume-title":"Microbiological Contamination Control in Pharmaceutical clean Rooms","author":"Halls","year":"2004"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1089\/omi.2017.0091","article-title":"Toward the drug factory microbiome: microbial community variations in antibiotic-producing clean rooms","volume":"22","author":"Hamdy","year":"2018","journal-title":"OMICS"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.chom.2013.11.008","article-title":"A view to a kill: the bacterial type VI secretion system","volume":"15","author":"Ho","year":"2014","journal-title":"Cell Host Microbe"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"3219","DOI":"10.5958\/0974-360X.2018.00592.9","article-title":"Review of FDA warning letters to pharmaceuticals: cause and effect analysis","volume":"11","author":"Jain","year":"2018","journal-title":"Res. J. Pharm. Technol."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"5114","DOI":"10.1038\/s41467-018-07641-9","article-title":"High throughput ANI analysis of 90K prokaryotic genomes reveals clear species boundaries","volume":"9","author":"Jain","year":"2018","journal-title":"Nat. Commun."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.jhazmat.2012.07.040","article-title":"Antibiotic resistance gene abundances associated with antibiotics and heavy metals in animal manures and agricultural soils adjacent to feedlots in Shanghai; China","volume":"235","author":"Ji","year":"2012","journal-title":"J. Hazard. Mater."},{"key":"ref27","first-page":"383","article-title":"Microbial diversity in pharmaceutical product recalls and environments","volume":"61","author":"Jimenez","year":"2007","journal-title":"PDA J. Pharm. Sci. Technol."},{"key":"ref28","first-page":"48","article-title":"Analysis of FDA enforcement reports (2012-2019) to determine the microbial diversity in contaminated non-sterile and sterile drugs","volume":"21","author":"Jimenez","year":"2019","journal-title":"Am. Pharm. Rev."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"104973","DOI":"10.1016\/j.ejps.2019.104973","article-title":"Culture independent approach reveals domination of human-oriented microbes in a pharmaceutical manufacturing facility","volume":"137","author":"Kawai","year":"2019","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"e35","DOI":"10.1093\/nar\/gkx1321","article-title":"PlasFlow: predicting plasmid sequences in metagenomic data using genome signatures","volume":"46","author":"Krawczyk","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"W78","DOI":"10.1093\/nar\/gkae268","article-title":"Interactive tree of life (iTOL) v6: recent updates to the phylogenetic tree display and annotation tool","volume":"52","author":"Letunic","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"106899","DOI":"10.1016\/j.envint.2021.106899","article-title":"Metagenomic evidence for co-occurrence of antibiotic, biocide and metal resistance genes in pigs","volume":"158","author":"Li","year":"2022","journal-title":"Environ. Int."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"2490","DOI":"10.1038\/ismej.2015.59","article-title":"Metagenomic and network analysis reveal wide distribution and co-occurrence of environmental antibiotic resistance genes","volume":"9","author":"Li","year":"2015","journal-title":"ISME J."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"142702","DOI":"10.1016\/j.scitotenv.2020.142702","article-title":"Co-selection of antibiotic resistance genes, and mobile genetic elements in the presence of heavy metals in poultry farm environments","volume":"755","author":"Mazhar","year":"2021","journal-title":"Sci. Total Environ."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"110829","DOI":"10.1016\/j.jobe.2024.110829","article-title":"Particle and bacterial colony emissions from garments and humans in pharmaceutical cleanrooms","volume":"97","author":"Meng","year":"2024","journal-title":"J. Build. Eng."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"109532","DOI":"10.1016\/j.vetmic.2022.109532","article-title":"A core genome multilocus sequence typing (cgMLST) analysis of Mycoplasma bovis isolates","volume":"273","author":"Menghwar","year":"2022","journal-title":"Vet. Microbiol."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1530","DOI":"10.1093\/molbev\/msaa015","article-title":"IQ-TREE 2: new models and efficient methods for phylogenetic inference in the genomic era","volume":"37","author":"Minh","year":"2020","journal-title":"Mol. Biol. Evol."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"2961","DOI":"10.3389\/fmicb.2019.02961","article-title":"Core\/whole genome multilocus sequence typing and core genome SNP-based typing of OXA-48-producing Klebsiella pneumoniae clinical isolates from Spain","volume":"10","author":"Miro","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"700","DOI":"10.3390\/microorganisms10040700","article-title":"Integronfinder 2.0: identification and analysis of integrons across bacteria, with a focus on antibiotic resistance in Klebsiella","volume":"10","author":"N\u00e9ron","year":"2022","journal-title":"Microorganisms."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1038\/nrmicro2182","article-title":"Staphylococcus epidermidis\u2014the 'accidental' pathogen","volume":"7","author":"Otto","year":"2009","journal-title":"Nat. Rev. Microbiol."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1111\/jam.12416","article-title":"Bacterial diversity in the indoor air of pharmaceutical environment","volume":"116","author":"Park","year":"2014","journal-title":"J. Appl. Microbiol."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1016\/j.bbrc.2015.12.083","article-title":"Analysis of the microbiome: advantages of whole genome shotgun versus 16S amplicon sequencing","volume":"469","author":"Ranjan","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.watres.2014.11.021","article-title":"Occurrence of antibiotics and antibiotic resistance genes in hospital and urban wastewaters and their impact on the receiving river","volume":"69","author":"Rodriguez-Mozaz","year":"2015","journal-title":"Water Res."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1093\/bib\/bbz010","article-title":"The global dissemination of bacterial infections necessitates the study of reverse genomic epidemiology","volume":"21","author":"Ruan","year":"2020","journal-title":"Brief. Bioinform."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1007\/s10096-013-1975-9","article-title":"Ralstonia spp.: emerging global opportunistic pathogens","volume":"33","author":"Ryan","year":"2014","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1186\/1471-2180-11-194","article-title":"Genotypic and phenotypic diversity of Ralstonia pickettii and Ralstonia insidiosa isolates from clinical and environmental sources including high-purity water. Diversity in Ralstonia pickettii","volume":"11","author":"Ryan","year":"2011","journal-title":"BMC Microbiol."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"392","DOI":"10.5731\/pdajpst.2011.00765","article-title":"A review of cleanroom microflora: types, trends, and patterns","volume":"65","author":"Sandle","year":"2011","journal-title":"PDA J. Pharm. Sci. Technol."},{"key":"ref48","first-page":"29","article-title":"Review of FDA warning letters for microbial bioburden issues (2001-2011)","volume":"44","author":"Sandle","year":"2012","journal-title":"Pharma Times"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"62","DOI":"10.5731\/pdajpst.2016.007252","article-title":"A QRM discussion of microbial contamination of non-sterile drug products, using FDA and EMA warning letters recorded between 2008 and 2016","volume":"72","author":"Santos","year":"2018","journal-title":"PDA J. Pharm. Sci. Technol."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"D32","DOI":"10.1093\/nar\/gkj014","article-title":"ISfinder: the reference Centre for bacterial insertion sequences","volume":"34","author":"Siguier","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1097\/qco.0000000000000743","article-title":"Techniques in bacterial strain typing: past, present, and future","volume":"34","author":"Simar","year":"2021","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1590\/S0042-96862002000200008","article-title":"Antimicrobial resistance: a global response","volume":"80","author":"Smith","year":"2002","journal-title":"Bull. World Health Organ."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"1327175","DOI":"10.3389\/fmicb.2024.1327175","article-title":"A comprehensive technology strategy for microbial identification and contamination investigation in the sterile drug manufacturing facility\u2014a case study","volume":"15","author":"Song","year":"2024","journal-title":"Front. Microbiol."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1038\/nrg3962","article-title":"Horizontal gene transfer: building the web of life","volume":"16","author":"Soucy","year":"2015","journal-title":"Nat. Rev. Genet."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"9730","DOI":"10.1021\/es401507k","article-title":"Long-term exposure to benzalkonium chloride disinfectants results in change of microbial community structure and increased antimicrobial resistance","volume":"47","author":"Tandukar","year":"2013","journal-title":"Environ. Sci. Technol."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"00139-19","DOI":"10.1128\/cmr.00139-19","article-title":"Burkholderia cepacia complex bacteria: a feared contamination risk in water-based pharmaceutical products","volume":"33","author":"Tavares","year":"2020","journal-title":"Clin. Microbiol. Rev."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1086\/595740","article-title":"Role of mgrA and sarA in methicillin-resistant Staphylococcus aureus autolysis and resistance to cell wall-active antibiotics","volume":"199","author":"Trotonda","year":"2009","journal-title":"J. Infect. Dis."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s42522-020-0010-1","article-title":"Typing methods based on whole genome sequencing data","volume":"2","author":"Uelze","year":"2020","journal-title":"One Health Outlook."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1111\/jam.12888","article-title":"A review of melanized (black) fungal contamination in pharmaceutical products--incidence, drug recall and control measures","volume":"120","author":"Vijayakumar","year":"2016","journal-title":"J. Appl. Microbiol."},{"key":"ref60","first-page":"4","article-title":"A review on fungal contamination in pharmaceutical products and phenotypic identification of contaminants by conventional","volume":"17","author":"Vijayakumar","year":"2012","journal-title":"Eur. J. Parenter. Pharm. Sci."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"567","DOI":"10.3390\/antibiotics4040567","article-title":"Co-selection of resistance to antibiotics, biocides and heavy metals, and its relevance to foodborne pathogens","volume":"4","author":"Wales","year":"2015","journal-title":"Antibiotics."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1186\/s12879-024-09228-w","article-title":"Persistent bacteremia caused by Ralstonia pickettii and Microbacterium: a case report","volume":"24","author":"Wang","year":"2024","journal-title":"BMC Infect. Dis."},{"key":"ref63","volume-title":"Cleanroom Technology: Fundamentals of Design, Testing and Operation","author":"Whyte","year":"2010"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"e1005595","DOI":"10.1371\/journal.pcbi.1005595","article-title":"Unicycler: resolving bacterial genome assemblies from short and long sequencing reads","volume":"13","author":"Wick","year":"2017","journal-title":"PLoS Comput. Biol."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1631\/jzus.2007.B0666","article-title":"Characterization of predominant bacteria isolates from clean rooms in a pharmaceutical production unit","volume":"8","author":"Wu","year":"2007","journal-title":"J. Zhejiang Univ. Sci. B"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"e56","DOI":"10.1002\/imt2.56","article-title":"Ggtree: a serialized data object for visualization of a phylogenetic tree and annotation data","volume":"1","author":"Xu","year":"2022","journal-title":"iMeta"},{"key":"ref67","doi-asserted-by":"publisher","first-page":"2263","DOI":"10.1093\/bioinformatics\/bty053","article-title":"ARGs-OAP v2.0 with an expanded SARG database and hidden Markov models for enhancement characterization and quantification of antibiotic resistance genes in environmental metagenomes","volume":"34","author":"Yin","year":"2018","journal-title":"Bioinformatics"},{"key":"ref68","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/j.watres.2016.10.042","article-title":"Co-occurrence of mobile genetic elements and antibiotic resistance genes in municipal solid waste landfill leachates: a preliminary insight into the role of landfill age","volume":"106","author":"Yu","year":"2016","journal-title":"Water Res."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1016\/j.scitotenv.2018.11.372","article-title":"Evidence for co-selection of antibiotic resistance genes and mobile genetic elements in metal polluted urban soils","volume":"656","author":"Zhao","year":"2019","journal-title":"Sci. Total Environ."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1807989\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T05:42:30Z","timestamp":1776231750000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1807989\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,15]]},"references-count":69,"alternative-id":["10.3389\/fmicb.2026.1807989"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2026.1807989","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,15]]},"article-number":"1807989"}}