{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T20:56:29Z","timestamp":1771102589076,"version":"3.50.1"},"reference-count":22,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Appl Environ Microbiol"],"published-print":{"date-parts":[[2025,1,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Because of the urgent need for new antibiotics to treat drug-resistant bacterial pathogens, we employed an assay that rapidly screens large quantities of compounds for their ability to interfere with bacterial protein synthesis, in particular, the delivery of amino acids to the ribosome via tRNA and elongation factor Tu (EF-Tu). We have identified a drug lead, named MGC-10, which kills Gram-positive bacteria, including methicillin-resistant\n              <jats:italic>Staphylococcus aureus<\/jats:italic>\n              (MRSA), with a MIC of 6 \u00b5M, while being harmless to mammalian cells\n              <jats:italic>in vitro<\/jats:italic>\n              in that concentration range. The antibacterial activity of MGC-10 was broad against over 50 strains of antibiotic-resistant samples obtained from hospital infections, where MGC-10 inhibited all tested strains of MRSA. Extensive selection and screening with MGC-10 did not yield any resistant strains, indicating it may have universal antibacterial activity against\n              <jats:italic>S. aureus<\/jats:italic>\n              . Pharmacokinetics performed in mice suggested that MGC-10 was too toxic for systemic use; however, it appears to have potential as a topical treatment for difficult-to-treat wounds or skin infections by Gram-positive pathogens such as MRSA. In a mouse skin-infection model with MRSA, MGC-10 performed as well or better than the present topical drug of choice, mupirocin. MGC-10 showed little, if any, accumulation in the livers of topically treated mice. These results bode well for the future use of MGC-10 in clinical application as it could be used to treat a broad range of\n              <jats:italic>S. aureus<\/jats:italic>\n              skin infections that are resistant to known antibiotics.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                There is a critical need for new antibiotics to treat bacterial infections caused by pathogens resistant to many if not all currently available antibiotics. We describe here the identification of a prospective new antibiotic from high-throughput screening of a chemical library. The screening was designed to detect the inhibition of formation of a complex required for bacterial protein synthesis in all bacteria, the \u201cternary complex,\u201d comprised of elongation factor Tu (EF-Tu), aminoacyl-tRNA, and GTP. The inhibitory compound, renamed MGC-10, was effective against all Gram-positive bacteria, including a wide variety of methicillin-resistant\n                <jats:italic>Staphylococcus aureus<\/jats:italic>\n                (MRSA) strains. Although apparently too toxic for systemic use, the compound was safe and effective for topical use for treating skin infections in a mouse model. No resistance to the compound has been detected thus far, suggesting the potential to develop this compound for topical use to treat infections, especially those caused by pathogens resistant to existing antibiotics.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/aem.02046-24","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T14:02:37Z","timestamp":1734962557000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Identification of an antibiotic from an HTS targeting EF-Tu:tRNA interaction: a prospective topical treatment for MRSA skin infections"],"prefix":"10.1128","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-7150-5885","authenticated-orcid":false,"given":"Wlodek","family":"Mandecki","sequence":"first","affiliation":[{"name":"Department of Microbiology, Biochemistry, & Molecular Genetics, Rutgers New Jersey Medical School","place":["Newark, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maxim","family":"Chudaev","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biochemistry, & Molecular Genetics, Rutgers New Jersey Medical School","place":["Newark, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjuan","family":"Ye","sequence":"additional","affiliation":[{"name":"National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH)","place":["Bethesda, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy Q.","family":"Wang","sequence":"additional","affiliation":[{"name":"National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH)","place":["Bethesda, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth J.","family":"Wilson","sequence":"additional","affiliation":[{"name":"National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH)","place":["Bethesda, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Xu","sequence":"additional","affiliation":[{"name":"National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH)","place":["Bethesda, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jisun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, Center for Immunity and Inflammation, Rutgers New Jersey Medical School","place":["Newark, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dane","family":"Parker","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, Center for Immunity and Inflammation, Rutgers New Jersey Medical School","place":["Newark, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5196-1571","authenticated-orcid":true,"given":"David","family":"Alland","sequence":"additional","affiliation":[{"name":"Public Health Research Institute, Rutgers New Jersey Medical School","place":["Newark, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pradeep","family":"Kumar","sequence":"additional","affiliation":[{"name":"Public Health Research Institute, Rutgers New Jersey Medical School","place":["Newark, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barry","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biochemistry & Molecular Genetics, Ruy V. Louren\u00e7o Center for Emerging and Re-Emerging Pathogens, Rutgers New Jersey Medical School","place":["Newark, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason H.","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biochemistry & Molecular Genetics, Ruy V. Louren\u00e7o Center for Emerging and Re-Emerging Pathogens, Rutgers New Jersey Medical School","place":["Newark, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0243-131X","authenticated-orcid":true,"given":"Barry","family":"Kreiswirth","sequence":"additional","affiliation":[{"name":"Center for Discovery & Innovation, Hackensack Meridian Health","place":["Nutley, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose R.","family":"Mediavilla","sequence":"additional","affiliation":[{"name":"Center for Discovery & Innovation, Hackensack Meridian Health","place":["Nutley, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan J.","family":"Marugan","sequence":"additional","affiliation":[{"name":"National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH)","place":["Bethesda, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark J.","family":"Henderson","sequence":"additional","affiliation":[{"name":"National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH)","place":["Bethesda, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6748-0884","authenticated-orcid":true,"given":"Emanuel","family":"Goldman","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Biochemistry, & Molecular Genetics, Rutgers New Jersey Medical School","place":["Newark, USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.mi.39.100185.003013"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41429-020-00387-x"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/gzt006"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/gzp079"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1089\/adt.2018.843"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00470a002"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsb787"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-37399-0"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1177\/108705719900400206"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.140.2.6480"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)02724-0"},{"key":"e_1_3_5_13_2","unstructured":"Centers for Disease Control and Prevention. 2024. 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