{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:33:08Z","timestamp":1787016788296,"version":"build-2736575974"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T00:00:00Z","timestamp":1709596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T00:00:00Z","timestamp":1709596800000},"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":["Microbiol Spectr"],"published-print":{"date-parts":[[2024,3,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The increasing prevalence of methicillin-resistant\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      (MRSA) has sparked global concern due to the dwindling availability of effective antibiotics. To increase our treatment options, researchers have investigated naturally occurring antimicrobial compounds and have identified MC21-A (C58), which has potent antimicrobial activity against MRSA. Recently, we have devised total synthesis schemes for C58 and its chloro-analog, C59. Here, we report that both compounds eradicate 90% of the 39 MRSA isolates tested [MIC\n                      <jats:sub>90<\/jats:sub>\n                      and minimum bactericidal concentration (MBC\n                      <jats:sub>90<\/jats:sub>\n                      )] at lower or comparable concentrations compared to several standard-of-care (SoC) antimicrobials including daptomycin, vancomycin, and linezolid. Furthermore, a stable, water-soluble sodium salt of C59, C59Na, demonstrates antimicrobial activity comparable to C59. C59, unlike vancomycin, kills stationary-phase MRSA in a dose-dependent manner and completely eradicates MRSA biofilms. In contrast to vancomycin, exposing MRSA to sub-MIC concentrations of C59 does not result in the emergence of spontaneous resistance. Similarly, in a multi-step study, C59 demonstrates a low propensity of resistance acquisition when compared to SoC antimicrobials, such as linezolid and clindamycin. Our findings suggest C58, C59, and C59Na are non-toxic to mammalian cells at concentrations that exert antimicrobial activity; the lethal dose at median cell viability (LD\n                      <jats:sub>50<\/jats:sub>\n                      ) is at least fivefold higher than the MBC\n                      <jats:sub>90<\/jats:sub>\n                      in the two mammalian cell lines tested. A morphological examination of the effects of C59 on a MRSA isolate suggests the inhibition of the cell division process as a mechanism of action. Our results demonstrate the potential of this naturally occurring compound and its analogs as non-toxic next-generation antimicrobials to combat MRSA infections\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      The rapid emergence of methicillin-resistant\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      (MRSA) isolates has precipitated a critical need for novel antibiotics. We have developed a one-pot synthesis method for naturally occurring compounds such as MC21-A (C58) and its chloro-analog, C59. Our findings demonstrate that these compounds kill MRSA isolates at lower or comparable concentrations to standard-of-care (SoC) antimicrobials. C59 eradicates MRSA cells in biofilms, which are notoriously difficult to treat with SoC antibiotics. Additionally, the lack of resistance development observed with C59 treatment is a significant advantage when compared to currently available antibiotics. Furthermore, these compounds are non-toxic to mammalian cell lines at effective concentrations. Our findings indicate the potential of these compounds to treat MRSA infections and underscore the importance of exploring natural products for novel antibiotics. Further investigation will be essential to fully realize the therapeutic potential of these next-generation antimicrobials to address the critical issue of antimicrobial resistance.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.01515-22","type":"journal-article","created":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T12:24:06Z","timestamp":1706617446000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":12,"title":["Antimicrobial activity of a natural compound and analogs against multi-drug-resistant Gram-positive pathogens"],"prefix":"10.1128","volume":"12","author":[{"given":"Kush N.","family":"Shah","sequence":"first","affiliation":[{"name":"Department of Microbial Pathogenesis &amp; Immunology, College of Medicine, Texas A&amp;M University Health Science Center, Bryan, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parth N.","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis &amp; Immunology, College of Medicine, Texas A&amp;M University Health Science Center, Bryan, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2540-0791","authenticated-orcid":true,"given":"Francesca O.","family":"Agobe","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis &amp; Immunology, College of Medicine, Texas A&amp;M University Health Science Center, Bryan, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7520-8362","authenticated-orcid":false,"given":"Kaitlyn","family":"Lovato","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Rice University, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4049-6832","authenticated-orcid":false,"given":"Hongyin","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Rice University, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5844-5710","authenticated-orcid":false,"given":"Oluwadara","family":"Ogun","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis &amp; Immunology, College of Medicine, Texas A&amp;M University Health Science Center, Bryan, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cason","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis &amp; Immunology, College of Medicine, Texas A&amp;M University Health Science Center, Bryan, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marium","family":"Yabe-Gill","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6849-177X","authenticated-orcid":true,"given":"Qingquan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis &amp; Immunology, College of Medicine, Texas A&amp;M University Health Science Center, Bryan, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan","family":"Sweatt","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis &amp; Immunology, College of Medicine, Texas A&amp;M University Health Science Center, Bryan, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhagath","family":"Chirra","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis &amp; Immunology, College of Medicine, Texas A&amp;M University Health Science Center, Bryan, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5254-6836","authenticated-orcid":false,"given":"Ricardo","family":"Mu\u00f1oz-Medina","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis &amp; Immunology, College of Medicine, Texas A&amp;M University Health Science Center, Bryan, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delaney E.","family":"Farmer","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis &amp; Immunology, College of Medicine, Texas A&amp;M University Health Science Center, Bryan, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3412-5894","authenticated-orcid":false,"given":"L\u00e1szl\u00f3","family":"K\u00fcrti","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Rice University, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2491-0389","authenticated-orcid":true,"given":"Carolyn L.","family":"Cannon","sequence":"additional","affiliation":[{"name":"Department of Microbial Pathogenesis &amp; 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Antibiotic resistance threats in the United States, 2013. In Prevention UCfDCa (Ed). US Centers for Disease Control and Prevention."},{"key":"e_1_3_3_3_2","volume-title":"Prevention UCfDCa (Ed)","author":"CDC","year":"2019","unstructured":"CDC. 2019. Antibiotic resistance threats in the United States, 2019. In Prevention UCfDCa (Ed). 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Yale J Biol Med 90:269\u2013281.","journal-title":"Yale J Biol Med"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2009.02.009"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14303"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0924-8579(03)00155-9"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.2.480-488.2003"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/np100506z"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1207\/s15327914nc5401_4"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1159483"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo049359m"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkn513"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03781-14"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1021\/nn3008383"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkf058"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02073-12"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-540-75418-3_10"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa025025"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.202000677"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01642-08"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1099\/13500872-145-6-1325"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3088"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00021-10"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2005.06.038"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2017.01.007"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2000.tb00554.x"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1093\/femsre\/fuv040"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.201600179"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biophys-121219-081703"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003592"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00204-21"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.11.052"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb.10.1.7507342"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja01865a018"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1039\/b719894a"},{"key":"e_1_3_3_42_2","volume-title":"Metal alkoxide complex, catalyst composition and preparation method of polycaprolactone or polylactide","author":"Dongmei C","year":"2017","unstructured":"Dongmei C, Liu X, Liu B, Li S, Liu D, Wu C. 2017. Metal alkoxide complex, catalyst composition and preparation method of polycaprolactone or polylactide. Changchun Institute of Applied Chemistry, Chinese Academy of Sciences."},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/cctc.201500743"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1021\/om400060s"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1039\/b404824e"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.10.4210-4219.2005"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.10.2740-2746.2000"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.molpharmaceut.8b01288"}],"container-title":["Microbiology Spectrum"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.01515-22","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/spectrum.01515-22","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T09:11:12Z","timestamp":1709629872000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/spectrum.01515-22"}},"subtitle":[],"editor":[{"given":"Prabagaran","family":"Narayanasamy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,3,5]]},"references-count":47,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3,5]]}},"alternative-id":["10.1128\/spectrum.01515-22"],"URL":"https:\/\/doi.org\/10.1128\/spectrum.01515-22","relation":{},"ISSN":["2165-0497"],"issn-type":[{"value":"2165-0497","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,5]]},"assertion":[{"value":"2022-05-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-01-30","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e01515-22"}}