{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T11:16:01Z","timestamp":1762686961131,"version":"build-2065373602"},"reference-count":96,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,5,4]],"date-time":"2024-05-04T00:00:00Z","timestamp":1714780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)","award":["398967434\u2014TRR261","N.a.","JP22H02738","JP22ama121039"],"award-info":[{"award-number":["398967434\u2014TRR261","N.a.","JP22H02738","JP22ama121039"]}]},{"name":"Medical Faculty of Bonn University","award":["398967434\u2014TRR261","N.a.","JP22H02738","JP22ama121039"],"award-info":[{"award-number":["398967434\u2014TRR261","N.a.","JP22H02738","JP22ama121039"]}]},{"name":"Studienstiftung des deutschen Volkes","award":["398967434\u2014TRR261","N.a.","JP22H02738","JP22ama121039"],"award-info":[{"award-number":["398967434\u2014TRR261","N.a.","JP22H02738","JP22ama121039"]}]},{"name":"J\u00fcrgen Manchot foundation","award":["398967434\u2014TRR261","N.a.","JP22H02738","JP22ama121039"],"award-info":[{"award-number":["398967434\u2014TRR261","N.a.","JP22H02738","JP22ama121039"]}]},{"name":"FEMHABIL, Medical Faculty, University of Bonn","award":["398967434\u2014TRR261","N.a.","JP22H02738","JP22ama121039"],"award-info":[{"award-number":["398967434\u2014TRR261","N.a.","JP22H02738","JP22ama121039"]}]},{"name":"JSPS KAKENHI Grant-in-Aid for Scientific Research (B)","award":["398967434\u2014TRR261","N.a.","JP22H02738","JP22ama121039"],"award-info":[{"award-number":["398967434\u2014TRR261","N.a.","JP22H02738","JP22ama121039"]}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","award":["398967434\u2014TRR261","N.a.","JP22H02738","JP22ama121039"],"award-info":[{"award-number":["398967434\u2014TRR261","N.a.","JP22H02738","JP22ama121039"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Chlamydial infections and diseases caused by filarial nematodes are global health concerns. However, treatment presents challenges due to treatment failures potentially caused by persisting Chlamydia and long regimens against filarial infections accompanied by low compliance. A new treatment strategy could be the targeting of the reduced peptidoglycan structures involved in cell division in the obligate intracellular bacteria Chlamydia and Wolbachia, the latter being obligate endosymbionts supporting filarial development, growth, and survival. Here, cell culture experiments with C. trachomatis and Wolbachia showed that the nucleoside antibiotics muraymycin and carbacaprazamycin interfere with bacterial cell division and induce enlarged, aberrant cells resembling the penicillin-induced persistence phenotype in Chlamydia. Enzymatic inhibition experiments with purified C. pneumoniae MraY revealed that muraymycin derivatives abolish the synthesis of the peptidoglycan precursor lipid I. Comparative in silico analyses of chlamydial and wolbachial MraY with the corresponding well-characterized enzyme in Aquifex aeolicus revealed a high degree of conservation, providing evidence for a similar mode of inhibition. Muraymycin D2 treatment eradicated persisting non-dividing C. trachomatis cells from an established penicillin-induced persistent infection. This finding indicates that nucleoside antibiotics may have additional properties that can break bacterial persistence.<\/jats:p>","DOI":"10.3390\/antibiotics13050421","type":"journal-article","created":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T15:05:01Z","timestamp":1715007901000},"page":"421","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The MraY Inhibitor Muraymycin D2 and Its Derivatives Induce Enlarged Cells in Obligate Intracellular Chlamydia and Wolbachia and Break the Persistence Phenotype in Chlamydia"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7443-4333","authenticated-orcid":false,"given":"Iris","family":"L\u00f6ckener","sequence":"first","affiliation":[{"name":"Institute for Pharmaceutical Microbiology (IPM), University of Bonn, University Hospital Bonn, Meckenheimer Allee 168, 53115 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lara Vanessa","family":"Behrmann","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jula","family":"Reuter","sequence":"additional","affiliation":[{"name":"Institute for Pharmaceutical Microbiology (IPM), University of Bonn, University Hospital Bonn, Meckenheimer Allee 168, 53115 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9823-2090","authenticated-orcid":false,"given":"Andrea","family":"Schiefer","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Kl\u00f6ckner","sequence":"additional","affiliation":[{"name":"Institute for Pharmaceutical Microbiology (IPM), University of Bonn, University Hospital Bonn, Meckenheimer Allee 168, 53115 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian","family":"Krannich","sequence":"additional","affiliation":[{"name":"Institute for Pharmaceutical Microbiology (IPM), University of Bonn, University Hospital Bonn, Meckenheimer Allee 168, 53115 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Otten","sequence":"additional","affiliation":[{"name":"Institute for Pharmaceutical Microbiology (IPM), University of Bonn, University Hospital Bonn, Meckenheimer Allee 168, 53115 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katja","family":"M\u00f6lleken","sequence":"additional","affiliation":[{"name":"Institute for Functional Microbial Genomics, Heinrich Heine University D\u00fcsseldorf, Universit\u00e4tsstra\u00dfe 1, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5345-5007","authenticated-orcid":false,"given":"Satoshi","family":"Ichikawa","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8671-3831","authenticated-orcid":false,"given":"Achim","family":"Hoerauf","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanja","family":"Schneider","sequence":"additional","affiliation":[{"name":"Institute for Pharmaceutical Microbiology (IPM), University of Bonn, University Hospital Bonn, Meckenheimer Allee 168, 53115 Bonn, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3096-2465","authenticated-orcid":false,"given":"Kenneth M.","family":"Pfarr","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Venusberg-Campus 1, 53127 Bonn, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, 53127 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beate","family":"Henrichfreise","sequence":"additional","affiliation":[{"name":"Institute for Pharmaceutical Microbiology (IPM), University of Bonn, University Hospital Bonn, Meckenheimer Allee 168, 53115 Bonn, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1016\/S0140-6736(08)60836-3","article-title":"Trachoma","volume":"371","author":"Wright","year":"2008","journal-title":"Lancet"},{"key":"ref_2","unstructured":"European Centre for Disease Prevention and Control (2022). ECDC. Annual Epidemiological Report for 2019, ECDC."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1097\/00007435-199207000-00001","article-title":"Pelvic Inflammatory Disease and Fertility: A Cohort Study of 1844 Women with Laparoscopically Verified Disease and 657 Control Women with Normal Laparoscopic Results","volume":"19","author":"Joesoef","year":"1992","journal-title":"Sex. Transm. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1016\/0002-9378(91)90559-A","article-title":"Genital Chlamydial Infections: Epidemiology and Reproductive Sequelae","volume":"164","author":"Cates","year":"1991","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_5","unstructured":"WHO (2016). WHO Guidelines for the Treatment of Chlamydia Trachomatis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1046\/j.1468-3083.2001.00342.x","article-title":"Electron Microscopic Evidence of Persistent Chlamydial Infection Following Treatment","volume":"15","author":"Bragina","year":"2001","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1097\/OLQ.0b013e3181a2a933","article-title":"Repeat Infection with Chlamydia and Gonorrhea among Females: A Systematic Review of the Literature","volume":"36","author":"Hosenfeld","year":"2009","journal-title":"Sex. Transm. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1086\/648734","article-title":"Repeated Chlamydia Trachomatis Genital Infections in Adolescent Women","volume":"201","author":"Batteiger","year":"2010","journal-title":"J. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1056\/NEJMoa041681","article-title":"Effect of Expedited Treatment of Sex Partners on Recurrent or Persistent Gonorrhea or Chlamydial Infection","volume":"352","author":"Golden","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1111\/2049-632X.12052","article-title":"Chlamydial Infection of the Gastrointestinal Tract: A Reservoir for Persistent Infection","volume":"68","author":"Yeruva","year":"2013","journal-title":"Pathog. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1016\/j.micinf.2012.07.017","article-title":"Chlamydia Muridarum Enters a Viable but Non-Infectious State in Amoxicillin-Treated BALB\/c Mice","volume":"14","author":"Kintner","year":"2012","journal-title":"Microbes Infect."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Lewis, M.E., Belland, R.J., AbdelRahman, Y.M., Beatty, W.L., Aiyar, A.A., Zea, A.H., Greene, S.J., Marrero, L., Buckner, L.R., and Tate, D.J. (2014). Morphologic and Molecular Evaluation of Chlamydia Trachomatis Growth in Human Endocervix Reveals Distinct Growth Patterns. Front. Cell Infect. Microbiol., 4.","DOI":"10.3389\/fcimb.2014.00071"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1128\/iai.48.2.592-596.1985","article-title":"Inhibition of Growth of Chlamydia Trachomatis by Human Gamma Interferon","volume":"48","author":"Shemer","year":"1985","journal-title":"Infect. Immun."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Skilton, R.J., Cutcliffe, L.T., Barlow, D., Wang, Y., Salim, O., Lambden, P.R., and Clarke, I.N. (2009). Penicillin Induced Persistence in Chlamydia Trachomatis: High Quality Time Lapse Video Analysis of the Developmental Cycle. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0007723"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1128\/iai.63.1.199-205.1995","article-title":"Reactivation of Persistent Chlamydia Trachomatis Infection in Cell Culture","volume":"63","author":"Beatty","year":"1995","journal-title":"Infect. Immun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1093\/jac\/dkh283","article-title":"Pre-Exposure of Infected Human Endometrial Epithelial Cells to Penicillin in Vitro Renders Chlamydia Trachomatis Refractory to Azithromycin","volume":"54","author":"Wyrick","year":"2004","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1128\/AAC.49.5.1787-1793.2005","article-title":"Bactericidal Activity of First-Choice Antibiotics against Gamma Interferon-Induced Persistent Infection of Human Epithelial Cells by Chlamydia Trachomatis","volume":"49","author":"Reveneau","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1128\/AAC.02097-13","article-title":"Induction of the Chlamydia Muridarum Stress\/Persistence Response Increases Azithromycin Treatment Failure in a Murine Model of Infection","volume":"58","author":"Kintner","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1006\/expr.1998.4383","article-title":"16S RDNA Phylogeny and Ultrastructural Characterization of Wolbachia Intracellular Bacteria of the Filarial Nematodes Brugia malayi, B. pahangi, and Wuchereria bancrofti","volume":"91","author":"Taylor","year":"1999","journal-title":"Exp. parasitol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0166-6851(98)00109-1","article-title":"Gene Structure, Activity and Localization of a Catalase from Intracellular Bacteria in Onchocerca volvulus","volume":"96","author":"Eckelt","year":"1998","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"34955","DOI":"10.1038\/srep34955","article-title":"Genomic Evidence for Plant-Parasitic Nematodes as the Earliest Wolbachia hosts","volume":"6","author":"Brown","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"20221518","DOI":"10.1098\/rspb.2022.1518","article-title":"A Highly Divergent Wolbachia with a Tiny Genome in an Insect-Parasitic Tylenchid Nematode","volume":"289","author":"Dudzic","year":"2022","journal-title":"Proc. Royal Soc. B"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"203","DOI":"10.2174\/138955706775475984","article-title":"Antibiotics Which Target the Wolbachia Endosymbionts of Filarial Parasites: A New Strategy for Control of Filariasis and Amelioration of Pathology","volume":"6","author":"Pfarr","year":"2006","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1111\/j.1365-3024.2009.01133.x","article-title":"Filariasis and Lymphoedema","volume":"31","author":"Pfarr","year":"2009","journal-title":"Parasite Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e1186","DOI":"10.1016\/S2214-109X(20)30286-2","article-title":"The Global Distribution of Lymphatic Filariasis, 2000\u20132018: A Geospatial Analysis","volume":"8","author":"Cromwell","year":"2020","journal-title":"Lancet Glob. Health"},{"key":"ref_26","unstructured":"WHO (2020). Ending the Neglect to Attain the Sustainable Development Goals: A Road Map for Neglected Tropical Diseases 2021\u20132030."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1126173","DOI":"10.3389\/fitd.2023.1126173","article-title":"Filariasis Research\u2014From Basic Research to Drug Development and Novel Diagnostics, over a Decade of Research at the Institute for Medical Microbiology, Immunology and Parasitology, Bonn, Germany","volume":"4","author":"Karunakaran","year":"2023","journal-title":"Front. Trop. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1016\/S0140-6736(10)60586-7","article-title":"Lymphatic Filariasis and Onchocerciasis","volume":"376","author":"Taylor","year":"2010","journal-title":"Lancet"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/nature12892","article-title":"A New Metabolic Cell-Wall Labelling Method Reveals Peptidoglycan in Chlamydia trachomatis","volume":"506","author":"Liechti","year":"2014","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Liechti, G., Kuru, E., Packiam, M., Hsu, Y.-P., Tekkam, S., Hall, E., Rittichier, J.T., VanNieuwenhze, M., Brun, Y.V., and Maurelli, A.T. (2016). Pathogenic Chlamydia Lack a Classical Sacculus but Synthesize a Narrow, Mid-Cell Peptidoglycan Ring, Regulated by MreB, for Cell Division. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005590"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e01342-21","DOI":"10.1128\/mBio.01342-21","article-title":"Discovery of a Diverse Set of Bacteria That Build Their Cell Walls without the Canonical Peptidoglycan Polymerase APBP","volume":"12","author":"Atwal","year":"2021","journal-title":"mBio"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1111\/j.1365-2958.2009.06815.x","article-title":"Functional Conservation of the Lipid II Biosynthesis Pathway in the Cell Wall-Less Bacteria Chlamydia and Wolbachia: Why Is Lipid II Needed?","volume":"73","author":"Henrichfreise","year":"2009","journal-title":"Mol. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.ijmm.2013.01.002","article-title":"Requirement of Lipid II Biosynthesis for Cell Division in Cell Wall-Less Wolbachia, Endobacteria of Arthropods and Filarial Nematodes","volume":"303","author":"Vollmer","year":"2013","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"R1158","DOI":"10.1016\/j.cub.2016.09.028","article-title":"Bacterial Surfaces: The Wall That SEDS Built","volume":"26","author":"Henrichfreise","year":"2016","journal-title":"Cur Biol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Abdelrahman, Y., Ouellette, S.P., Belland, R.J., and Cox, J.V. (2016). Polarized Cell Division of Chlamydia trachomatis. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005866"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"12588","DOI":"10.1038\/s41598-020-69397-x","article-title":"Penicillin-Binding Proteins Regulate Multiple Steps in the Polarized Cell Division Process of Chlamydia","volume":"10","author":"Cox","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1111\/j.1365-2958.2012.08100.x","article-title":"Chlamydia Co-Opts the Rod Shape-Determining Proteins MreB and Pbp2 for Cell Division","volume":"85","author":"Ouellette","year":"2012","journal-title":"Mol. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Liechti, G.W. (2021). Localized Peptidoglycan Biosynthesis in Chlamydia Trachomatis Conforms to the Polarized Division and Cell Size Reduction Developmental Models. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.733850"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1128\/AAC.45.1.303-305.2001","article-title":"Affinities of \u03b2-Lactams for Penicillin Binding Proteins of Chlamydia Trachomatis and Their Antichlamydial Activities","volume":"45","author":"Storey","year":"2001","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1093\/jac\/47.5.659","article-title":"In Vitro Activity of Antimicrobial Agents against the Endosymbiont Wolbachia pipientis","volume":"47","author":"Hermans","year":"2001","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1128\/JB.185.4.1218-1228.2003","article-title":"In Vitro and In Vivo Functional Activity of Chlamydia MurA, a UDP-N.-Acetylglucosamine Enolpyruvyl Transferase Involved in Peptidoglycan Synthesis and Fosfomycin Resistance","volume":"185","author":"McCoy","year":"2003","journal-title":"J. Bacteriol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1111\/j.1749-6632.1974.tb43277.x","article-title":"The Mechanism of Action of Fosfomycin (Phosphonomycin)","volume":"235","author":"Kahan","year":"1974","journal-title":"Ann. N. Y Acad. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"10260","DOI":"10.1021\/ja017748h","article-title":"Structures of the Muraymycins, Novel Peptidoglycan Biosynthesis Inhibitors","volume":"124","author":"McDonald","year":"2002","journal-title":"J. Am. Chem. Soc."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"580","DOI":"10.7164\/antibiotics.56.580","article-title":"Caprazamycin B, A Novel Anti-Tuberculosis Antibiotic, from Streptomyces sp.","volume":"56","author":"Igarashi","year":"2003","journal-title":"J. Antibiot."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1021\/ml100057z","article-title":"Synthesis and Biological Evaluation of Muraymycin Analogues Active against Anti-Drug-Resistant Bacteria","volume":"1","author":"Tanino","year":"2010","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/ja.2005.41","article-title":"Caprazamycins, Novel Lipo-Nucleoside Antibiotics, from Streptomyces sp.","volume":"58","author":"Igarashi","year":"2005","journal-title":"J. Antibiot."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"8421","DOI":"10.1021\/jm200906r","article-title":"Mechanistic Analysis of Muraymycin Analogues: A Guide to the Design of MraY Inhibitors","volume":"54","author":"Tanino","year":"2011","journal-title":"J. Med. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1021\/ml5000096","article-title":"Expansion of Antibacterial Spectrum of Muraymycins toward Pseudomonas aeruginosa","volume":"5","author":"Takeoka","year":"2014","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1021\/id5000376","article-title":"Carbacaprazamycins: Chemically Stable Analogues of the Caprazamycin Nucleoside Antibiotics","volume":"1","author":"Ichikawa","year":"2015","journal-title":"ACS Infect. Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/nature17636","article-title":"Structural Insights into Inhibition of Lipid I Production in Bacterial Cell Wall Synthesis","volume":"533","author":"Chung","year":"2016","journal-title":"Nature"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1086\/505432","article-title":"Different Growth Rates of Chlamydia trachomatis Biovars Reflect Pathotype","volume":"194","author":"Miyairi","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5379","DOI":"10.1128\/AAC.00553-10","article-title":"In Vitro Activities of Several Antimicrobial Agents against Recently Isolated and Genotyped Chlamydia trachomatis Urogenital Serovars D through K","volume":"54","author":"Donati","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1093\/infdis\/jis341","article-title":"Corallopyronin A Specifically Targets and Depletes Essential Obligate Wolbachia Endobacteria from Filarial Nematodes In Vivo","volume":"206","author":"Schiefer","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2917","DOI":"10.1038\/s41467-019-10957-9","article-title":"Chemical Logic of MraY Inhibition by Antibacterial Nucleoside Natural Products","volume":"10","author":"Mashalidis","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1046\/j.1365-2958.1999.01623.x","article-title":"Topological Analysis of the MraY Protein Catalysing the First Membrane Step of Peptidoglycan Synthesis","volume":"34","author":"Bouhss","year":"1999","journal-title":"Mol. Microbiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1128\/JB.186.6.1747-1757.2004","article-title":"Phospho-N-Acetyl-Muramyl-Pentapeptide Translocase from Escherichia coli: Catalytic Role of Conserved Aspartic Acid Residues","volume":"186","author":"Lloyd","year":"2004","journal-title":"J. Bacteriol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"8919","DOI":"10.1021\/bi8006274","article-title":"Active Site Mapping of MraY, a Member of the Polyprenyl-Phosphate N-Acetylhexosamine 1-Phosphate Transferase Superfamily, Catalyzing the First Membrane Step of Peptidoglycan Biosynthesis","volume":"47","author":"Henry","year":"2008","journal-title":"Biochemistry"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1126\/science.1236501","article-title":"Crystal Structure of MraY, an Essential Membrane Enzyme for Bacterial Cell Wall Synthesis","volume":"341","author":"Chung","year":"2013","journal-title":"Science"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"5123","DOI":"10.1016\/j.bmc.2008.03.020","article-title":"Structure\u2013Activity Relationship of Truncated Analogs of Caprazamycins as Potential Anti-Tuberculosis Agents","volume":"16","author":"Hirano","year":"2008","journal-title":"Bioorg Med. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/S0960-894X(00)00714-9","article-title":"Synthesis of Analogues of the O-\u03b2-d-Ribofuranosyl Nucleoside Moiety of Liposidomycins. Part 2: Role of the Hydroxyl Groups upon the Inhibition of MraY","volume":"11","author":"Dini","year":"2001","journal-title":"Bioorg Med. Chem. Lett."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/S0960-894X(00)00715-0","article-title":"Synthesis of Analogues of the O-\u03b2-d-Ribofuranosyl Nucleoside Moiety of Liposidomycins. Part 1: Contribution of the Amino Group and the Uracil Moiety upon the Inhibition of MraY","volume":"11","author":"Dini","year":"2001","journal-title":"Bioorg Med. Chem. Lett."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1093\/jac\/dkx392","article-title":"Chlamydia Trachomatis Antimicrobial Susceptibility in Colorectal and Endocervical Cells","volume":"73","author":"Foschi","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1099\/jmm.0.023887-0","article-title":"Effects of Antibiotics on Chlamydia Trachomatis Viability as Determined by Real-Time Quantitative PCR","volume":"60","author":"Peuchant","year":"2011","journal-title":"J. Med. Microbiol."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Otten, C., De Benedetti, S., Gaballah, A., B\u00fchl, H., Kl\u00f6ckner, A., Brauner, J., Sahl, H.-G., and Henrichfreise, B. (2015). Co-Solvents as Stabilizing Agents during Heterologous Overexpression in Escherichia coli\u2014Application to Chlamydial Penicillin-Binding Protein 6. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0122110"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e00023-21","DOI":"10.1128\/mBio.00023-21","article-title":"Regulation of the Mitochondrion-Fatty Acid Axis for the Metabolic Reprogramming of Chlamydia Trachomatis during Treatment with \u03b2-Lactam Antimicrobials","volume":"12","author":"Shima","year":"2021","journal-title":"mBio"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"8478","DOI":"10.1073\/pnas.1331135100","article-title":"Genomic Transcriptional Profiling of the Developmental Cycle of Chlamydia trachomatis","volume":"100","author":"Belland","year":"2003","journal-title":"Proc. Nat. Acad. Sci. USA"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"De Benedetti, S., B\u00fchl, H., Gaballah, A., Kl\u00f6ckner, A., Otten, C., Schneider, T., Sahl, H.-G., and Henrichfreise, B. (2014). Characterization of Serine Hydroxymethyltransferase GlyA as a Potential Source of D-Alanine in Chlamydia pneumoniae. Front. Cell Infect. Microbiol., 4.","DOI":"10.3389\/fcimb.2014.00019"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1007\/s00203-011-0784-8","article-title":"Biochemical Characterisation of the Chlamydial MurF Ligase, and Possible Sequence of the Chlamydial Peptidoglycan Pentapeptide Stem","volume":"194","author":"Patin","year":"2012","journal-title":"Arch. Microbiol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1128\/jb.163.1.208-212.1985","article-title":"Effect of Growth Conditions on Peptidoglycan Content and Cytoplasmic Steps of Its Biosynthesis in Escherichia coli","volume":"163","year":"1985","journal-title":"J. Bacteriol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.1099\/mic.0.29032-0","article-title":"The Effect of Penicillin on Chlamydia trachomatis DNA Replication","volume":"152","author":"Lambden","year":"2006","journal-title":"Microbiology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1038\/nature19331","article-title":"SEDS Proteins Are a Widespread Family of Bacterial Cell Wall Polymerases","volume":"537","author":"Meeske","year":"2016","journal-title":"Nature"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/s41564-018-0345-x","article-title":"FtsW Is a Peptidoglycan Polymerase That Is Functional Only in Complex with Its Cognate Penicillin-Binding Protein","volume":"4","author":"Taguchi","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Shahab, M., Verma, M., Pathak, M., Mitra, K., and Misra-Bhattacharya, S. (2014). Cloning, Expression and Characterization of UDP-N-Acetylglucosamine Enolpyruvyl Transferase (MurA) from Wolbachia endosymbiont of Human Lymphatic Filarial Parasite Brugia malayi. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0099884"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1111\/j.1365-2958.2005.04661.x","article-title":"Characterization of Chlamydia MurC-Ddl, a Fusion Protein Exhibiting D-Alanyl-D-Alanine Ligase Activity Involved in Peptidoglycan Synthesis and D-Cycloserine Sensitivity","volume":"57","author":"McCoy","year":"2005","journal-title":"Mol. Microbiol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1021\/acschembio.9b00664","article-title":"Mechanisms of Incorporation for D-Amino Acid Probes That Target Peptidoglycan Biosynthesis","volume":"14","author":"Kuru","year":"2019","journal-title":"ACS Chem. Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1038\/s41467-019-09356-x","article-title":"Coordination of Capsule Assembly and Cell Wall Biosynthesis in Staphylococcus aureus","volume":"10","author":"Rausch","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Mann, P.A., M\u00fcller, A., Wolff, K.A., Fischmann, T., Wang, H., Reed, P., Hou, Y., Li, W., M\u00fcller, C.E., and Xiao, J. (2016). Chemical Genetic Analysis and Functional Characterization of Staphylococcal Wall Teichoic Acid 2-Epimerases Reveals Unconventional Antibiotic Drug Targets. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005585"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1128\/jb.162.1.391-397.1985","article-title":"Release of Cell Wall Peptides into Culture Medium by Exponentially Growing Escherichia coli","volume":"162","author":"Goodell","year":"1985","journal-title":"J. Bacteriol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e01128-19","DOI":"10.1128\/mBio.01128-19","article-title":"A SpoIID Homolog Cleaves Glycan Strands at the Chlamydial Division Septum","volume":"10","author":"Jacquier","year":"2019","journal-title":"mBio"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"4201","DOI":"10.1038\/ncomms5201","article-title":"AmiA Is a Penicillin Target Enzyme with Dual Activity in the Intracellular Pathogen Chlamydia pneumoniae","volume":"5","author":"Otten","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Reuter, J., Otten, C., Jacquier, N., Lee, J., Mengin-Lecreulx, D., L\u00f6ckener, I., Kluj, R., Mayer, C., Corona, F., and Dannenberg, J. (2023). An NlpC\/P60 Protein Catalyzes a Key Step in Peptidoglycan Recycling at the Intersection of Energy Recovery, Cell Division and Immune Evasion in the Intracellular Pathogen Chlamydia trachomatis. PLoS Pathog., 19.","DOI":"10.1371\/journal.ppat.1011047"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/ni945","article-title":"An Essential Role for NOD1 in Host Recognition of Bacterial Peptidoglycan Containing Diaminopimelic Acid","volume":"4","author":"Chamaillard","year":"2003","journal-title":"Nat. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"5509","DOI":"10.1074\/jbc.C200673200","article-title":"Host Recognition of Bacterial Muramyl Dipeptide Mediated through NOD2","volume":"278","author":"Inohara","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.jri.2008.12.004","article-title":"Functional Expression of Pattern Recognition Receptors in Tissues of the Human Female Reproductive Tract","volume":"80","author":"Hart","year":"2009","journal-title":"J. Reprod. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"409","DOI":"10.4161\/auto.6.3.11305","article-title":"Nod Proteins Link Bacterial Sensing and Autophagy","volume":"6","author":"Travassos","year":"2010","journal-title":"Autophagy"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.chom.2014.04.001","article-title":"The Immune Receptor NOD1 and Kinase RIP2 Interact with Bacterial Peptidoglycan on Early Endosomes to Promote Autophagy and Inflammatory Signaling","volume":"15","author":"Irving","year":"2014","journal-title":"Cell Host Microbe"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e685-20","DOI":"10.1128\/IAI.00685-20","article-title":"Persistence Alters the Interaction between Chlamydia trachomatis and Its Host Cell","volume":"89","author":"Brockett","year":"2021","journal-title":"Infect. Immun."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"11660","DOI":"10.1073\/pnas.1514026112","article-title":"Structural Characterization of Muropeptides from Chlamydia trachomatis Peptidoglycan by Mass Spectrometry Resolves \u201cChlamydial Anomaly\u201d","volume":"112","author":"Packiam","year":"2015","journal-title":"Proc. Nat. Acad. Sci. USA"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.4049\/jimmunol.177.2.1240","article-title":"Wolbachia Endosymbiotic Bacteria of Brugia malayi Mediate Macrophage Tolerance to TLR- and CD40-Specific Stimuli in a MyD88\/TLR2-Dependent Manner","volume":"177","author":"Turner","year":"2006","journal-title":"J. Immunol."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Stirling, D.R., Swain-Bowden, M.J., Lucas, A.M., Carpenter, A.E., Cimini, B.A., and Goodman, A. (2021). CellProfiler 4: Improvements in Speed, Utility and Usability. BMC Bioinform., 22.","DOI":"10.1186\/s12859-021-04344-9"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1128\/AAC.50.3.922-927.2006","article-title":"Rate of Elimination of Wolbachia pipientis by Doxycycline in Vitro Increases Following Drug Withdrawal","volume":"50","author":"Makepeace","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"14371","DOI":"10.1073\/pnas.0804090105","article-title":"Tuning Escherichia coli for Membrane Protein Overexpression","volume":"105","author":"Wagner","year":"2008","journal-title":"Proc. Nat. Acad. Sci. USA"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1111\/j.1574-6968.1991.tb04451.x","article-title":"One-Step Purification Procedure for UDP-N-Acetylmuramyl-Peptide Murein Precursors from Bacillus cereus","volume":"78","author":"Kohlrausch","year":"1991","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1093\/glycob\/8.6.557","article-title":"Characterization of the Lipid-Carrier Involved in the Synthesis of Enterobacterial Common Antigen (ECA) and Identification of a Novel Phosphoglyceride in a Mutant of Salmonella typhimurium Defective in ECA Synthesis","volume":"8","author":"Rick","year":"1998","journal-title":"Glycobiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/nprot.2015.053","article-title":"The Phyre2 Web Portal for Protein Modeling, Prediction and Analysis","volume":"10","author":"Kelley","year":"2015","journal-title":"Nat. Protoc."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1002\/pro.3943","article-title":"UCSF ChimeraX: Structure Visualization for Researchers, Educators, and Developers","volume":"30","author":"Pettersen","year":"2021","journal-title":"Protein Sci."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/13\/5\/421\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:39:28Z","timestamp":1760107168000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/13\/5\/421"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,4]]},"references-count":96,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2024,5]]}},"alternative-id":["antibiotics13050421"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics13050421","relation":{},"ISSN":["2079-6382"],"issn-type":[{"type":"electronic","value":"2079-6382"}],"subject":[],"published":{"date-parts":[[2024,5,4]]}}}