{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T05:04:16Z","timestamp":1780463056596,"version":"3.54.1"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Universidade Federal Do Tri\u00e2ngulo Mineiro"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Braz J Microbiol"],"published-print":{"date-parts":[[2026,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Enterococcus faecium<\/jats:italic>\n                    is a Gram-positive bacteria that infects the human gastrointestinal tract and it is a leading cause of hospital-acquired infections, due to its ability to cause various types of infections, such as endocarditis, bacteremia, urinary tract infections, and others, exacerbated by its multidrug resistance, notably to vancomycin. Because they are linked to major infections that are difficult to manage, and also due to the widespread acquisition of resistance genes, management remains difficult. This study employs pangenomic analyses and subtractive genomics to explore genetic diversity and identify novel therapeutic targets across 20 human-derived\n                    <jats:italic>E. faecium<\/jats:italic>\n                    genomes. Phylogenomic analyses revealed four distinct clades, with genomic rearrangements and horizontal gene transfer events underscoring adaptive evolution. Comparative genomics identified 20 pathogenicity islands and 12 resistance islands, alongside pan-resistome profiling highlighting prevalent resistance to aminoglycosides, elfamycins, and glycopeptides (e.g., vancomycin in 14\/20 strains). Core genome analyses, filtered for non-human homologs, prioritized cytoplasmic proteins critical for survival. Subtractive genomics predicted five high-confidence drug targets: phosphocarrier protein HPr (metabolic regulation), GNAT family N-acetyltransferase (antibiotic resistance), translation initiation factor IF-1 (protein synthesis), HU family DNA-binding protein (genome stability), and a sugar-binding domain protein (nutrient uptake). Structural modeling identified these targets as druggable with conserved roles in bacterial viability. This integrative approach elucidates\n                    <jats:italic>E. faecium\u2019s<\/jats:italic>\n                    genomic plasticity and resistance mechanisms while proposing candidates for targeted therapies, addressing the urgent need for novel interventions against this resilient pathogen.\n                  <\/jats:p>","DOI":"10.1007\/s42770-026-01983-z","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T04:18:16Z","timestamp":1780460296000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pangenomics insights of enterococcus faecium human isolates and identification of novel therapeutic targets by in silico subtractive genomics"],"prefix":"10.1007","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1402-3484","authenticated-orcid":false,"given":"Yngrid Vict\u00f3ria Cassiano","family":"Mascarenhas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8813-8850","authenticated-orcid":false,"given":"Andrei Giacchetto","family":"Felice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2568-6729","authenticated-orcid":false,"given":"Felipe Lucas","family":"Zen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5865-3651","authenticated-orcid":false,"given":"Victor Augusto Sallum","family":"Ceballos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7299-3724","authenticated-orcid":false,"given":"Siomar","family":"de Castro Soares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"1983_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2025.107381","volume":"201","author":"Y Wang","year":"2025","unstructured":"Wang Y, Xu W, Guo S et al (2025) Enterococci for human health: a friend or foe? Microb Pathog 201:107381","journal-title":"Microb Pathog"},{"issue":"1","key":"1983_CR2","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1128\/CMR.3.1.46","volume":"3","author":"BE Murray","year":"1990","unstructured":"Murray BE (1990) The life and times of the Enterococcus. Clin Microbiol Rev 3(1):46\u201365","journal-title":"Clin Microbiol Rev"},{"key":"1983_CR3","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.mib.2017.11.030","volume":"41","author":"W Gao","year":"2018","unstructured":"Gao W, Howden BP, Stinear TP (2018) Evolution of virulence in Enterococcus faecium, a hospital-adapted opportunistic pathogen. Curr Opin Microbiol 41:76\u201382","journal-title":"Curr Opin Microbiol"},{"issue":"2","key":"1983_CR4","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1590\/S0036-46652014000200002","volume":"56","author":"L Furlaneto-Maia","year":"2014","unstructured":"Furlaneto-Maia L, Rocha KR, Siqueira VLD, Furlaneto MC (2014) Comparison between automated system and PCR-based method for identification and antimicrobial susceptibility profile of clinical Enterococcus spp. Rev Inst Med Trop Sao Paulo 56(2):97\u2013103","journal-title":"Rev Inst Med Trop Sao Paulo"},{"issue":"8","key":"1983_CR5","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1086\/533452","volume":"197","author":"LB Rice","year":"2008","unstructured":"Rice LB (2008) Federal Funding for the Study of Antimicrobial Resistance in Nosocomial Pathogens: No ESKAPE. J Infect Dis 197(8):1079\u20131081","journal-title":"J Infect Dis"},{"key":"1983_CR6","doi-asserted-by":"crossref","unstructured":"Gorrie C, Higgs C, Carter G, Stinear TP, Howden B (2019) Genomics of vancomycin-resistant Enterococcus faecium. Microb Genom. ;5(7)","DOI":"10.1099\/mgen.0.000283"},{"issue":"4","key":"1983_CR7","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1016\/j.idc.2020.08.004","volume":"34","author":"WR Miller","year":"2020","unstructured":"Miller WR, Murray BE, Rice LB, Arias CA (2020) Resistance in Vancomycin-Resistant Enterococci. Infect Dis Clin North Am 34(4):751\u2013771","journal-title":"Infect Dis Clin North Am"},{"issue":"1","key":"1983_CR8","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1186\/s13756-020-00770-1","volume":"9","author":"X Zhou","year":"2020","unstructured":"Zhou X, Willems RJL, Friedrich AW, Rossen JWA, Bathoorn E (2020) Enterococcus faecium: from microbiological insights to practical recommendations for infection control and diagnostics. Antimicrob Resist Infect Control 9(1):130","journal-title":"Antimicrob Resist Infect Control"},{"issue":"6","key":"1983_CR9","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1016\/j.gde.2005.09.006","volume":"15","author":"D Medini","year":"2005","unstructured":"Medini D, Donati C, Tettelin H, Masignani V, Rappuoli R (2005) The microbial pan-genome. Curr Opin Genet Dev 15(6):589\u2013594","journal-title":"Curr Opin Genet Dev"},{"issue":"SUPPL. 1","key":"1983_CR10","doi-asserted-by":"publisher","first-page":"4599","DOI":"10.1073\/pnas.1000071108","volume":"108","author":"EE Hansen","year":"2011","unstructured":"Hansen EE, Lozupone CA, Rey FE, Wu M, Guruge JL, Narra A et al (2011) Pan-genome of the dominant human gut-associated archaeon, Methanobrevibacter smithii, studied in twins. Proc Natl Acad Sci U S A 108(SUPPL. 1):4599\u2013606","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"1983_CR11","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1002\/ddr.20413","volume":"72","author":"D Barh","year":"2011","unstructured":"Barh D, Tiwari S, Jain N, Ali A, Santos AR, Misra AN et al (2011) In silico subtractive genomics for target identification in human bacterial pathogens. Drug Dev Res 72(2):162\u2013177","journal-title":"Drug Dev Res"},{"key":"1983_CR12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0039107","author":"J \u00c5gren","year":"2012","unstructured":"\u00c5gren J, Sundstr\u00f6m A, H\u00e5fstr\u00f6m T, Segerman B (2012) Gegenees: fragmented alignment of multiple genomes for determining phylogenomic distances and genetic signatures unique for specified target groups. PLoS One. https:\/\/doi.org\/10.1371\/journal.pone.0039107","journal-title":"PLoS One"},{"issue":"2","key":"1983_CR13","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1093\/molbev\/msj030","volume":"23","author":"DH Huson","year":"2006","unstructured":"Huson DH, Bryant D (2006) Application of phylogenetic networks in evolutionary studies. Mol Biol Evol 23(2):254\u201367. https:\/\/doi.org\/10.1093\/molbev\/msj030","journal-title":"Mol Biol Evol"},{"issue":"Pt2","key":"1983_CR14","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1099\/ijs.0.059774-0","volume":"64","author":"M Kim","year":"2014","unstructured":"Kim M, Oh HS, Park SC, Chun J (2014) Towards a taxonomic coherence between average nucleotide identity and 16S rRNA gene sequence similarity for species demarcation of prokaryotes. Int J Syst Evol Microbiol 64(Pt2):346\u2013351","journal-title":"Int J Syst Evol Microbiol"},{"key":"1983_CR15","doi-asserted-by":"publisher","unstructured":"Darling AE, Mau B, Perna NT, Progressivemauve (2010) Multiple genome alignment with gene gain, loss and rearrangement. PLoS One [Internet]. ;5(6). Available from: http:\/\/dx.plos.org\/https:\/\/doi.org\/10.1371\/journal.pone.0011147","DOI":"10.1371\/journal.pone.0011147"},{"key":"1983_CR16","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.jbiotec.2015.09.008","volume":"232","author":"SC Soares","year":"2016","unstructured":"Soares SC, Geyik H, Ramos RTJ, de S\u00e1 PHCG, Barbosa EGV, Baumbach J et al (2016) GIPSy: genomic island prediction software. J Biotechnol 232:2\u201311","journal-title":"J Biotechnol"},{"key":"1983_CR17","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-12-402","author":"NF Alikhan","year":"2011","unstructured":"Alikhan NF, Petty NK, Ben Zakour NL, Beatson SA (2011) BLAST Ring Image Generator (BRIG): simple prokaryote genome comparisons. BMC Genomics. https:\/\/doi.org\/10.1186\/1471-2164-12-402","journal-title":"BMC Genomics"},{"issue":"1","key":"1983_CR18","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s12859-019-3335-y","volume":"21","author":"Y He","year":"2020","unstructured":"He Y, Zhou X, Chen Z, Deng X, Gehring A, Ou H et al (2020) PRAP: Pan Resistome analysis pipeline. BMC Bioinformatics 21(1):20","journal-title":"BMC Bioinformatics"},{"key":"1983_CR19","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-015-0721-2","author":"DM Emms","year":"2015","unstructured":"Emms DM, Kelly S (2015) OrthoFinder: solving fundamental biases in whole genome comparisons dramatically improves orthogroup inference accuracy. Genome Biol. https:\/\/doi.org\/10.1186\/s13059-015-0721-2","journal-title":"Genome Biol"},{"issue":"1","key":"1983_CR20","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1186\/1471-2105-10-421","volume":"10","author":"C Camacho","year":"2009","unstructured":"Camacho C, Coulouris G, Avagyan V, Ma N, Papadopoulos J, Bealer K et al (2009) BLAST+: architecture and applications. BMC Bioinformatics 10(1):421","journal-title":"BMC Bioinformatics"},{"issue":"1","key":"1983_CR21","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1002\/pmic.200800195","volume":"9","author":"A Barinov","year":"2009","unstructured":"Barinov A, Loux V, Hammani A, Nicolas P, Langella P, Ehrlichh D et al (2009) Prediction of surface exposed proteins in Streptococcus pyogenes, with a potential application to other Gram-positive bacteria. Proteomics 9(1):61\u201373. https:\/\/doi.org\/10.1002\/pmic.200800195","journal-title":"Proteomics"},{"key":"1983_CR22","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-11-610","author":"PVSZ Capriles","year":"2010","unstructured":"Capriles PVSZ, Guimar\u00e3es ACR, Otto TD, Miranda AB, Dardenne LE, Degrave WM (2010) Structural modelling and comparative analysis of homologous, analogous and specific proteins from Trypanosoma cruzi versus Homo sapiens: putative drug targets for Chagas\u2019 disease treatment. BMC Genomics. https:\/\/doi.org\/10.1186\/1471-2164-11-610","journal-title":"BMC Genomics"},{"key":"1983_CR23","doi-asserted-by":"crossref","unstructured":"UniProt (2019) UniProt: a worldwide hub of protein knowledge. Nucleic Acids Res [Internet]. ;47(D1):D506\u201315. Available from: https:\/\/academic.oup.com\/nar\/article\/47\/D1\/D506\/5160987","DOI":"10.1093\/nar\/gky1049"},{"key":"1983_CR24","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2020.00246","author":"CN Cavasotto","year":"2020","unstructured":"Cavasotto CN, Aucar MG (2020) High-throughput docking using quantum mechanical scoring. Front Chem. https:\/\/doi.org\/10.3389\/fchem.2020.00246","journal-title":"Front Chem"},{"issue":"2","key":"1983_CR25","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1107\/S1600576725001669","volume":"58","author":"M Kumar","year":"2025","unstructured":"Kumar M, Rathore RS (2025) RamPlot: a webserver to draw 2D, 3D and assorted Ramachandran (\u03c6, \u03c8) maps. J Appl Crystallogr 58(2):630\u2013636","journal-title":"J Appl Crystallogr"},{"issue":"16","key":"1983_CR26","doi-asserted-by":"publisher","first-page":"2785","DOI":"10.1002\/jcc.21256","volume":"30","author":"MM Garrett","year":"2009","unstructured":"Garrett MM, Ruth H, William L, Michel FS, Richard KB, G DS et al (2009) AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem 30(16):2785\u20135791. https:\/\/doi.org\/10.1002\/jcc.21256","journal-title":"J Comput Chem"},{"key":"1983_CR27","doi-asserted-by":"crossref","unstructured":"F\u00e4hrrolfes R, Bietz S, Flachsenberg F, Meyder A, Nittinger E, Otto T et al (2017) Proteins Plus: A web portal for structure analysis of macromolecules. Nucleic Acids Res [Internet]. ;45(W1):W337\u201343. Available from: https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/28472372","DOI":"10.1093\/nar\/gkx333"},{"key":"1983_CR28","doi-asserted-by":"publisher","DOI":"10.1098\/rsos.190907","author":"TCV Rodrigues","year":"2019","unstructured":"Rodrigues TCV, Jaiswal AK, De Sarom A, Oliveira LDC, Oliveira CJF, Ghosh P et al (2019) Reverse vaccinology and subtractive genomics reveal new therapeutic targets against Mycoplasma pneumoniae: a causative agent of pneumonia. R Soc Open Sci. https:\/\/doi.org\/10.1098\/rsos.190907","journal-title":"R Soc Open Sci"},{"issue":"2","key":"1983_CR29","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1002\/jcc.21334","volume":"31","author":"T Oleg","year":"2010","unstructured":"Oleg T, Arthur JO (2010) AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 31(2):455\u201361. https:\/\/doi.org\/10.1002\/jcc.21334","journal-title":"J Comput Chem"},{"issue":"13","key":"1983_CR30","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1002\/jcc.20084","volume":"25","author":"EF Pettersen","year":"2004","unstructured":"Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC et al (2004) UCSF Chimera - a visualization system for exploratory research and analysis. J Comput Chem 25(13):1605\u201312. https:\/\/doi.org\/10.1002\/jcc.20084","journal-title":"J Comput Chem"},{"key":"1983_CR31","doi-asserted-by":"crossref","unstructured":"Top J, Arredondo-Alonso S, Sch\u00fcrch AC, Puranen S, Pesonen M, Pensar J et al (2020) Genomic rearrangements uncovered by genome-wide co-evolution analysis of a major nosocomial pathogen, Enterococcus faecium. Microb Genom. ;6(12)","DOI":"10.1099\/mgen.0.000488"},{"key":"1983_CR32","doi-asserted-by":"crossref","unstructured":"Silva-Pereira TT, Soler-Camargo NC, Guimar\u00e3es AMS (2024) Diversification of gene content in the Mycobacterium tuberculosis complex is determined by phylogenetic and ecological signatures. Microbiol Spectr. ;12(2)","DOI":"10.1128\/spectrum.02289-23"},{"key":"1983_CR33","doi-asserted-by":"crossref","unstructured":"Dong Y, Chen S, Cheng S, Zhou W, Ma Q, Chen Z et al (2019) Natural selection and repeated patterns of molecular evolution following allopatric divergence. Elife. ;8","DOI":"10.7554\/eLife.45199"},{"key":"1983_CR34","doi-asserted-by":"crossref","unstructured":"Tokuda M, Shintani M (2024) Microbial evolution through horizontal gene transfer by mobile genetic elements. Microb Biotechnol. ;17(1)","DOI":"10.1111\/1751-7915.14408"},{"key":"1983_CR35","doi-asserted-by":"crossref","unstructured":"van Hal SJ, Ip CLC, Ansari MA, Wilson DJ, Espedido BA, Jensen SO et al (2016) Evolutionary dynamics of Enterococcus faecium reveals complex genomic relationships between isolates with independent emergence of vancomycin resistance. Microb Genom. ;2(1)","DOI":"10.1099\/mgen.0.000048"},{"issue":"4","key":"1983_CR36","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1093\/sysbio\/syaa068","volume":"71","author":"C Simon","year":"2022","unstructured":"Simon C (2022) An Evolving View of Phylogenetic Support. Syst Biol 71(4):921\u2013928","journal-title":"Syst Biol"},{"key":"1983_CR37","doi-asserted-by":"crossref","unstructured":"Schwartzman JA, Lebreton F, Salamzade R, Shea T, Martin MJ, Schaufler K et al (2024) Global diversity of enterococci and description of 18 previously unknown species. Proceedings of the National Academy of Sciences. ;121(10)","DOI":"10.1073\/pnas.2310852121"},{"issue":"15","key":"1983_CR38","doi-asserted-by":"publisher","first-page":"4528","DOI":"10.1128\/AEM.00650-13","volume":"79","author":"Y Getachew","year":"2013","unstructured":"Getachew Y, Hassan L, Zakaria Z, Abdul Aziz S (2013) Genetic Variability of Vancomycin-Resistant Enterococcus faecium and Enterococcus faecalis Isolates from Humans, Chickens, and Pigs in Malaysia. Appl Environ Microbiol 79(15):4528\u20134533","journal-title":"Appl Environ Microbiol"},{"key":"1983_CR39","doi-asserted-by":"crossref","unstructured":"Garc\u00eda-Solache M, Rice LB (2019) The Enterococcus: a Model of Adaptability to Its Environment. Clin Microbiol Rev. ;32(2)","DOI":"10.1128\/CMR.00058-18"},{"key":"1983_CR40","unstructured":"Kristich CJ, Rice LB, Arias CA (2014) Enterococcal Infection\u2014Treatment and Antibiotic Resistance"},{"key":"1983_CR41","doi-asserted-by":"crossref","unstructured":"Li J, Tai C, Deng Z, Zhong W, He Y, Ou HY (2017) VRprofile: gene-cluster-detection-based profiling of virulence and antibiotic resistance traits encoded within genome sequences of pathogenic bacteria. Brief Bioinform. ;bbw141","DOI":"10.1093\/bib\/bbw141"},{"key":"1983_CR42","doi-asserted-by":"crossref","unstructured":"Simner PJ, Humphries RM (2023) Special Phenotypic Methods for Detecting Antibacterial Resistance. ClinMicroNow. Wiley, pp 1\u201334","DOI":"10.1002\/9781683674849.mcm0076"},{"issue":"8","key":"1983_CR43","doi-asserted-by":"publisher","first-page":"2016","DOI":"10.1128\/jcm.32.8.2016-2018.1994","volume":"32","author":"A Miele","year":"1994","unstructured":"Miele A, Goldstein BP, Bandera M, Jarvis C, Resconi A, Williams RJ (1994) Differential susceptibilities of enterococcal species to elfamycin antibiotics. J Clin Microbiol 32(8):2016\u20132018","journal-title":"J Clin Microbiol"},{"issue":"12","key":"1983_CR44","doi-asserted-by":"publisher","first-page":"3163","DOI":"10.1021\/acsinfecdis.0c00467","volume":"6","author":"V Yarlagadda","year":"2020","unstructured":"Yarlagadda V, Medina R, Johnson TA, Koteva KP, Cox G, Thaker MN et al (2020) Resistance-Guided Discovery of Elfamycin Antibiotic Producers with Antigonococcal Activity. ACS Infect Dis 6(12):3163\u20133173","journal-title":"ACS Infect Dis"},{"issue":"9","key":"1983_CR45","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.3390\/antibiotics10091095","volume":"10","author":"M Rima","year":"2021","unstructured":"Rima M, Rima M, Fajloun Z, Sabatier JM, Bechinger B, Naas T (2021) Antimicrobial Peptides: A Potent Alternative to Antibiotics. Antibiotics 10(9):1095","journal-title":"Antibiotics"},{"key":"1983_CR46","doi-asserted-by":"crossref","unstructured":"Tymoszewska A, Szyli\u0144ska M, Aleksandrzak-Piekarczyk T (2023) The LiaFSR-LiaX System Mediates Resistance of Enterococcus faecium to Peptide Antibiotics and to Aureocin A53- and Enterocin L50-Like Bacteriocins. Microbiol Spectr. ;11(3)","DOI":"10.1128\/spectrum.00343-23"},{"issue":"4","key":"1983_CR47","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1016\/j.ccc.2013.06.006","volume":"29","author":"E Rubinstein","year":"2013","unstructured":"Rubinstein E, Keynan Y (2013) Vancomycin-Resistant Enterococci. Crit Care Clin 29(4):841\u2013852","journal-title":"Crit Care Clin"},{"key":"1983_CR48","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.jgg.2014.07.002","volume":"42","author":"P Natarajan","year":"2015","unstructured":"Natarajan P, Parani M (2015) First complete genome sequence of a probiotic Enterococcus faecium strain T-110 and its comparative genome analysis with pathogenic and non-pathogenic Enterococcus faecium genomes. J Genet Genomics 42:43\u20136. https:\/\/doi.org\/10.1016\/j.jgg.2014.07.002","journal-title":"J Genet Genomics"},{"key":"1983_CR49","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics12081327","volume":"12","author":"EJ Im","year":"2023","unstructured":"Im EJ, Lee H-Y, Kim M, Kim M-K (2023) Evaluation of enterococcal probiotic usage and review of potential health benefits, safety, and risk of antibiotic-resistant strain emergence. Antibiotics Basel 12:1327. https:\/\/doi.org\/10.3390\/antibiotics12081327","journal-title":"Antibiotics Basel"},{"key":"1983_CR50","doi-asserted-by":"crossref","unstructured":"Bender JK, Fiedler S, Klare I, Werner G (2015) Complete Genome Sequence of the Gut Commensal and Laboratory Strain Enterococcus faecium 64\/3. Genome Announc. ;3(6)","DOI":"10.1128\/genomeA.01275-15"},{"issue":"4","key":"1983_CR51","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1093\/jac\/dkaa541","volume":"76","author":"TM Wagner","year":"2021","unstructured":"Wagner TM, Janice J, Sivertsen A, Sj\u00f6gren I, Sundsfjord A, Hegstad K (2021) Alternative vanHAX promoters and increased vanA -plasmid copy number resurrect silenced glycopeptide resistance in Enterococcus faecium. J Antimicrob Chemother 76(4):876\u2013882","journal-title":"J Antimicrob Chemother"},{"issue":"1","key":"1983_CR52","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1128\/jb.176.1.198-205.1994","volume":"176","author":"HS Cummings","year":"1994","unstructured":"Cummings HS, Hershey JW (1994) Translation initiation factor IF1 is essential for cell viability in Escherichia coli. J Bacteriol 176(1):198\u2013205","journal-title":"J Bacteriol"},{"issue":"4","key":"1983_CR53","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1016\/j.jmb.2006.10.024","volume":"365","author":"KK Swinger","year":"2007","unstructured":"Swinger KK, Rice PA (2007) Structure-based Analysis of HU\u2013DNA Binding. J Mol Biol 365(4):1005\u20131016","journal-title":"J Mol Biol"},{"key":"1983_CR54","first-page":"1","volume":"13","author":"A Grove","year":"2011","unstructured":"Grove A (2011) Functional Evolution of Bacterial Histone-Like HU Proteins. Curr Issues Mol Biol 13:1\u201312","journal-title":"Curr Issues Mol Biol"},{"issue":"3","key":"1983_CR55","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1016\/j.jmb.2009.02.017","volume":"387","author":"D de Sanctis","year":"2009","unstructured":"de Sanctis D, McVey CE, Enguita FJ, Carrondo MA (2009) Crystal structure of the full-length sorbitol operon regulator SorC from Klebsiella pneumoniae: structural evidence for a novel transcriptional regulation mechanism. J Mol Biol 387(3):759\u201370","journal-title":"J Mol Biol"},{"key":"1983_CR56","doi-asserted-by":"crossref","unstructured":"Van Tartwijk FW, Kaminski CF (2022) Protein Condensation, Cellular Organization, and Spatiotemporal Regulation of Cytoplasmic Properties. Adv Biol. ;6(11)","DOI":"10.1002\/adbi.202101328"},{"issue":"4","key":"1983_CR57","doi-asserted-by":"publisher","first-page":"225","DOI":"10.3233\/ISB-2009-0399","volume":"9","author":"D Barh","year":"2009","unstructured":"Barh D, Kumar A (2009) In silico Identification of Candidate Drug and Vaccine Targets from Various Pathways in Neisseria gonorrhoeae. Silico Biology: J Biol Syst Model Multi-Scale Simul 9(4):225\u2013231","journal-title":"Silico Biology: J Biol Syst Model Multi-Scale Simul"},{"issue":"1","key":"1983_CR58","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s13321-020-00424-9","volume":"12","author":"M Sorokina","year":"2020","unstructured":"Sorokina M, Steinbeck C (2020) Review on natural products databases: where to find data in 2020. J Cheminform 12(1):20","journal-title":"J Cheminform"}],"container-title":["Brazilian Journal of Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s42770-026-01983-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s42770-026-01983-z","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s42770-026-01983-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T04:18:24Z","timestamp":1780460304000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s42770-026-01983-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,3]]},"references-count":58,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,12]]}},"alternative-id":["1983"],"URL":"https:\/\/doi.org\/10.1007\/s42770-026-01983-z","relation":{},"ISSN":["1517-8382","1678-4405"],"issn-type":[{"value":"1517-8382","type":"print"},{"value":"1678-4405","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,3]]},"assertion":[{"value":"9 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All authors declare that they have no competing interests with this manuscript.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"166"}}