{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T17:36:42Z","timestamp":1774978602522,"version":"3.50.1"},"reference-count":33,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T00:00:00Z","timestamp":1640131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003243","name":"Ministry of Health of the Czech Republic","doi-asserted-by":"publisher","award":["NU20-03-00309"],"award-info":[{"award-number":["NU20-03-00309"]}],"id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"publisher"}]},{"name":"BIOCEV","award":["CZ.1.05\/1.1.00\/02.0109"],"award-info":[{"award-number":["CZ.1.05\/1.1.00\/02.0109"]}]},{"name":"Institute of Biotechnology RVO","award":["86652036"],"award-info":[{"award-number":["86652036"]}]},{"DOI":"10.13039\/501100001824","name":"Czech Science Foundation","doi-asserted-by":"publisher","award":["20-09811Y"],"award-info":[{"award-number":["20-09811Y"]}],"id":[{"id":"10.13039\/501100001824","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001824","name":"Czech Science Foundation","doi-asserted-by":"publisher","award":["19-08176S"],"award-info":[{"award-number":["19-08176S"]}],"id":[{"id":"10.13039\/501100001824","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004240","name":"Czech Academy of Sciences","doi-asserted-by":"publisher","award":["LQ200202002"],"award-info":[{"award-number":["LQ200202002"]}],"id":[{"id":"10.13039\/501100004240","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Teicoplanin is a natural lipoglycopeptide antibiotic with a similar activity spectrum as vancomycin; however, it has with the added benefit to the patient of low cytotoxicity. Both teicoplanin and vancomycin antibiotics are actively used in medical practice in the prophylaxis and treatment of severe life-threatening infections caused by gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, Enterococcus faecium and Clostridium difficile. The expression of vancomycin Z (vanZ), encoded either in the vancomycin A (vanA) glycopeptide antibiotic resistance gene cluster or in the genomes of E. faecium, as well as Streptococcus pneumoniae and C. difficile, was shown to specifically compromise the antibiotic efficiency through the inhibition of teicoplanin binding to the bacterial surface. However, the exact mechanisms of this action and protein structure remain unknown. In this study, the three-dimensional structure of VanZ from E. faecium EnGen0191 was predicted by using the I-TASSER web server. Based on the VanZ structure, a benzimidazole based ligand was predicted to bind to the VanZ by molecular docking. Importantly, this new ligand, named G3K, was further confirmed to specifically inhibit VanZ-mediated resistance to teicoplanin in vivo.<\/jats:p>","DOI":"10.3390\/ijms23010097","type":"journal-article","created":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T10:24:52Z","timestamp":1640168692000},"page":"97","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Specific Inhibition of VanZ-Mediated Resistance to Lipoglycopeptide Antibiotics"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1175-7194","authenticated-orcid":false,"given":"Vishma Pratap","family":"Sur","sequence":"first","affiliation":[{"name":"Laboratory of Reproductive Biology, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV, Prumyslova 595, 252 50 Vestec, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4985-7115","authenticated-orcid":false,"given":"Aninda","family":"Mazumdar","sequence":"additional","affiliation":[{"name":"Laboratory for Biology of Secondary Metabolism, Institute of Microbiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir","family":"Vimberg","sequence":"additional","affiliation":[{"name":"Laboratory for Biology of Secondary Metabolism, Institute of Microbiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4414-6787","authenticated-orcid":false,"given":"Tommaso","family":"Stefani","sequence":"additional","affiliation":[{"name":"Laboratory for Biology of Secondary Metabolism, Institute of Microbiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ladislav","family":"Androvic","sequence":"additional","affiliation":[{"name":"Department of Polymer and Colloid Immunotherapeutics, Institute of Macromolecular Chemistry of the Czech Academy of Sciences, Heyrovskeho namesti 2, 162 06 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucie","family":"Kracikova","sequence":"additional","affiliation":[{"name":"Department of Polymer and Colloid Immunotherapeutics, Institute of Macromolecular Chemistry of the Czech Academy of Sciences, Heyrovskeho namesti 2, 162 06 Prague, Czech Republic"},{"name":"Department of Polymers, Faculty of Chemical Technology, University of Chemistry and Technology, Technicka 5, 166 28 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Laga","sequence":"additional","affiliation":[{"name":"Department of Polymer and Colloid Immunotherapeutics, Institute of Macromolecular Chemistry of the Czech Academy of Sciences, Heyrovskeho namesti 2, 162 06 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zdenek","family":"Kamenik","sequence":"additional","affiliation":[{"name":"Laboratory for Biology of Secondary Metabolism, Institute of Microbiology of the Czech Academy of Sciences, Videnska 1083, 142 20 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6837-2148","authenticated-orcid":false,"given":"Katerina","family":"Komrskova","sequence":"additional","affiliation":[{"name":"Laboratory of Reproductive Biology, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEV, Prumyslova 595, 252 50 Vestec, Czech Republic"},{"name":"Department of Zoology, Faculty of Science, Charles University, Vinicna 7, 128 44 Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mazumdar, A., Haddad, Y., Milosavljevic, V., Michalkova, H., Guran, R., Bhowmick, S., and Moulick, A. (2020). Peptide-carbon quantum dots conjugate, derived from human retinoic acid receptor responder protein 2, against antibiotic-resistant gram positive and gram negative pathogenic bacteria. Nanomaterials, 10.","DOI":"10.3390\/nano10020325"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.31083\/j.jmcm.2021.01.208","article-title":"Antimicrobial peptides-An alternative candidates to antibiotics against Staphylococcus aureus and its antibiotic-resistant strains","volume":"4","author":"Mazumdar","year":"2021","journal-title":"J. Mol. Clin. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.3389\/fmicb.2020.01963","article-title":"Characterization and in vitro analysis of probiotic-derived peptides against multi drug resistance bacterial infections","volume":"11","author":"Mazumdar","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Sur, V.P., Mazumdar, A., Kopel, P., Mukherjee, S., V\u00edtek, P., Michalkova, H., Vaculovi\u010dov\u00e1, M., and Moulick, A. (2020). A novel ruthenium based coordination compound against pathogenic bacteria. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072656"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Sur, V.P., Mazumdar, A., Ashrafi, A., Mukherjee, A., Milosavljevic, V., Michalkova, H., Kopel, P., Richtera, L., and Moulick, A. (2020). A Novel Biocompatible Titanium\u2013Gadolinium Quantum Dot as a Bacterial Detecting Agent with High Antibacterial Activity. Nanomaterials, 10.","DOI":"10.3390\/nano10040778"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Sur, V.P., Kominkova, M., Buchtova, Z., Dolezelikova, K., Zitka, O., and Moulick, A. (2019). CdSe QD Biosynthesis in Yeast Using Tryptone-Enriched Media and Their Conjugation with a Peptide Hecate for Bacterial Detection and Killing. Nanomaterials, 9.","DOI":"10.3390\/nano9101463"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1146\/annurev.biochem.78.082907.145923","article-title":"Multidrug resistance in bacteria","volume":"78","author":"Nikaido","year":"2009","journal-title":"Annu. Rev. Biochem."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Xie, O., Slavin, M.A., Teh, B.W., Bajel, A., Douglas, A.P., and Worth, L.J. (2020). Epidemiology, treatment and outcomes of bloodstream infection due to vancomycin-resistant enterococci in cancer patients in a vanB endemic setting. BMC Infect. Dis., 20.","DOI":"10.1186\/s12879-020-04952-5"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.diagmicrobio.2014.02.018","article-title":"Co-colonization of vanA and vanB Enterococcus faecium of clonal complex 17 in a patient with bacteremia due to vanA E. faecium","volume":"79","author":"Seol","year":"2014","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.2147\/IDR.S160975","article-title":"Novel vancomycin\u2013peptide conjugate as potent antibacterial agent against vancomycin-resistant Staphylococcus aureus","volume":"11","author":"Jelinkova","year":"2018","journal-title":"Infect. Drug Resist."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4895","DOI":"10.1021\/ja00329a044","article-title":"Structure elucidation of the teicoplanin antibiotics","volume":"106","author":"Barna","year":"1984","journal-title":"J. Am. Chem. Soc."},{"key":"ref_12","first-page":"276","article-title":"Phenotypic and genotypic traits of vancomycin-resistant enterococci in a public hospital: The first vanB-positive Enterococcus faecium isolates","volume":"46","author":"Aksu","year":"2012","journal-title":"Mikrobiyoloji Bul."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/0378-1119(94)00851-I","article-title":"The vanZ gene of Tn1546 from Enterococcus faecium BM4147 confers resistance to teicoplanin","volume":"154","author":"Arthur","year":"1995","journal-title":"Gene"},{"key":"ref_14","unstructured":"Mazumdar, A. (2020). Studies on the Effect of Antimicrobial Peptides Conjugated with Nanoparticles on Pathogenic Bacteria. [Ph.D. Thesis, Mendelova univerzita v Brn\u011b, Agronomick\u00e1 Fakulta]."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.vetmic.2017.04.030","article-title":"Streptococcus suis serotype 9 strain GZ0565 contains a type VII secretion system putative substrate EsxA that contributes to bacterial virulence and a vanZ-like gene that confers resistance to teicoplanin and dalbavancin in Streptococcus agalactiae","volume":"205","author":"Lai","year":"2017","journal-title":"Vet. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.anaerobe.2018.06.013","article-title":"Examination of the Clostridioides (Clostridium) difficile VanZ ortholog, CD1240","volume":"53","author":"Woods","year":"2018","journal-title":"Anaerobe"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1128\/AAC.42.8.2055","article-title":"vanA gene cluster in a vancomycin-resistant clinical isolate of Bacillus circulans","volume":"42","author":"Ligozzi","year":"1998","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.bpj.2017.06.042","article-title":"An efficient method for estimating the hydrodynamic radius of disordered protein conformations","volume":"113","author":"Nygaard","year":"2017","journal-title":"Biophys. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1021\/acs.biomac.7b01813","article-title":"Peptoid backbone flexibility dictates its interaction with water and surfaces: A molecular dynamics investigation","volume":"19","author":"Prakash","year":"2018","journal-title":"Biomacromolecules"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5814","DOI":"10.1021\/acs.jpcb.9b04326","article-title":"Branched-Chain Fatty Acid Content Modulates Structure, Fluidity, and Phase in Model Microbial Cell Membranes","volume":"123","author":"Mostofian","year":"2019","journal-title":"J. Phys. Chem. B"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1016\/j.bbalip.2016.06.003","article-title":"Broad substrate specificity of phosphotransbutyrylase from Listeria monocytogenes: A potential participant in an alternative pathway for provision of acyl CoA precursors for fatty acid biosynthesis","volume":"1861","author":"Sirobhushanam","year":"2016","journal-title":"Biochim Biophys Acta"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"566","DOI":"10.3389\/fmicb.2020.00566","article-title":"VanZ Reduces the Binding of Lipoglycopeptide Antibiotics to Staphylococcus aureus and Streptococcus pneumoniae Cells","volume":"11","author":"Vimberg","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Goud, N.S., Kumar, P., and Bharath, R.D. (2020). Recent Developments of Target-Based Benzimidazole Derivatives as Potential Anticancer Agents. Heterocycles-Synthesis and Biological Activities, IntechOpen.","DOI":"10.5772\/intechopen.90758"},{"key":"ref_24","unstructured":"Sur, V.P. (2020). Metal Based Coordinate Compounds and Nanoparticles as an Alternative of Antibiotics against Resistant Bacterial Strains. [Ph.D. Thesis, Mendelova Univerzita v Brn\u011b, Agronomick\u00e1 Fakulta]."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2163","DOI":"10.1021\/jm2014138","article-title":"Structure-based design of potent and ligand-efficient inhibitors of CTX-M class A \u03b2-lactamase","volume":"55","author":"Nichols","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1007\/s00284-011-9868-6","article-title":"Vancomycin-resistance Transferability from VanA Enterococci to Staphylococcus aureus","volume":"62","author":"Bondi","year":"2011","journal-title":"Curr. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1038\/nprot.2010.5","article-title":"I-TASSER: A unified platform for automated protein structure and function prediction","volume":"5","author":"Roy","year":"2010","journal-title":"Nat. Protoc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1093\/bioinformatics\/btt607","article-title":"Protter: Interactive protein feature visualization and integration with experimental proteomic data","volume":"30","author":"Omasits","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1107\/S0021889892009944","article-title":"PROCHECK: A program to check the stereochemical quality of protein structures","volume":"26","author":"Laskowski","year":"1993","journal-title":"J. Appl. Crystallogr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1007\/BF00228148","article-title":"AQUA and PROCHECK-NMR: Programs for checking the quality of protein structures solved by NMR","volume":"8","author":"Laskowski","year":"1996","journal-title":"J. Biomol. NMR"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1002\/jcc.20945","article-title":"CHARMM-GUI: A web-based graphical user interface for CHARMM","volume":"29","author":"Jo","year":"2008","journal-title":"J. Comput. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3396","DOI":"10.1080\/07391102.2019.1657499","article-title":"Structure-based virtual screening, molecular dynamics simulation and MM-PBSA toward identifying the inhibitors for two-component regulatory system protein NarL of Mycobacterium Tuberculosis","volume":"38","author":"Kumar","year":"2020","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Sur, V.P., Sen, M.K., and Komrskova, K. (2021). In Silico Identification and Validation of Organic Triazole Based Ligands as Potential Inhibitory Drug Compounds of SARS-CoV-2 Main Protease. Molecules, 26.","DOI":"10.26434\/chemrxiv-2021-wk8d1"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/1\/97\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:51:19Z","timestamp":1760169079000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/1\/97"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,22]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["ijms23010097"],"URL":"https:\/\/doi.org\/10.3390\/ijms23010097","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,22]]}}}