{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T05:12:46Z","timestamp":1783660366687,"version":"3.55.0"},"reference-count":38,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000738","name":"Department of Veterans\u2019 Affairs CDA-2","doi-asserted-by":"publisher","award":["IK2BX005911"],"award-info":[{"award-number":["IK2BX005911"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH","award":["R01 AI72219"],"award-info":[{"award-number":["R01 AI72219"]}]},{"name":"NIH","award":["R01 AI147609"],"award-info":[{"award-number":["R01 AI147609"]}]},{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs","doi-asserted-by":"publisher","award":["I01BX001725"],"award-info":[{"award-number":["I01BX001725"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs","doi-asserted-by":"publisher","award":["IK6BX004470"],"award-info":[{"award-number":["IK6BX004470"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs","doi-asserted-by":"publisher","award":["IK6BX005390"],"award-info":[{"award-number":["IK6BX005390"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: Corallopyronin A (CorA) is a bacterial RNA polymerase inhibitor that binds a site distinct from rifamycins, but its activity across the ESKAPEE pathogen panel and its translational potential remain incompletely defined. Methods: CorA activity was evaluated against representative ESKAPEE pathogens using broth microdilution assays \u00b1 polymyxin B nonapeptide (PMBN). Activity was benchmarked against rifampin (Rif). Resistance, cross-resistance, serum activity, in vivo efficacy in the Galleria mellonella wax moth larva model, and biofilm disruption were assessed. Results: CorA inhibited Acinetobacter baumannii (minimal inhibitory concentration [MIC] = 16\u201332 \u00b5g\/mL), including MDR isolates, with susceptibility enhanced 4\u201332-fold by efflux disruption or membrane permeabilization. In contrast, most other Gram-negative ESKAPEE pathogens required PMBN for activity, while Gram-positive organisms were intrinsically susceptible. Rif was consistently more potent than CorA across the panel. Rif-resistant A. baumannii and Klebsiella pneumoniae remained fully susceptible to CorA, confirming the absence of cross-resistance. Fractional inhibitory concentration (FIC) index analysis revealed pharmacological indifference between CorA and Rif, with no synergy or antagonism detected. CorA activity was abolished in 50% serum conditions and was not restored by PMBN, consistent with serum sequestration; no efficacy was observed in a G. mellonella infection model at doses up to 20 mg\/kg despite Rif demonstrating significant protection. Notably, CorA reduced established A. baumannii biofilms by \u223c3\u20134 log colony-forming units per mL (CFU\/mL) across concentrations \u22654\u00d7 MIC after 24 h of treatment. Conclusions: CorA exhibits selective activity against A. baumannii and retains efficacy against Rif-resistant strains. While high serum binding reduces in vitro activity and efficacy was not observed in the G. mellonella model at a lower dose than in other in vivo models, established in vivo activity against other pathogens demonstrates that serum binding does not preclude therapeutic utility. These findings highlight both the translational considerations for CorA against ESKAPEE pathogens and potential niches for its application, including filarial nematodes, biofilm-associated infections and combination strategies.<\/jats:p>","DOI":"10.3390\/antibiotics15070665","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T17:27:31Z","timestamp":1783531651000},"page":"665","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Activity of Corallopyronin A Against ESKAPEE Pathogens: Potential and Translational Implications"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2659-2919","authenticated-orcid":false,"given":"Jennifer M.","family":"Colquhoun","sequence":"first","affiliation":[{"name":"Research Service, Atlanta VA Medical Center, Decatur, GA 30033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kara W.","family":"Marshall","sequence":"additional","affiliation":[{"name":"Research Service, Atlanta VA Medical Center, Decatur, GA 30033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Grosse","sequence":"additional","affiliation":[{"name":"Department of Microbial Drugs, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, 38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birthe","family":"Sandargo","sequence":"additional","affiliation":[{"name":"Department of Microbial Drugs, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, 38124 Braunschweig, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3096-2465","authenticated-orcid":false,"given":"Kenneth","family":"Pfarr","sequence":"additional","affiliation":[{"name":"Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, University of Bonn, 53113 Bonn, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, 53113 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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, University Hospital Bonn, University of Bonn, 53113 Bonn, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, 53113 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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, University Hospital Bonn, University of Bonn, 53113 Bonn, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, 53113 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9303-8777","authenticated-orcid":false,"given":"William M.","family":"Shafer","sequence":"additional","affiliation":[{"name":"Research Service, Atlanta VA Medical Center, Decatur, GA 30033, USA"},{"name":"Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30307, USA"},{"name":"Emory Antibiotic Resistance Center, Emory University School of Medicine, Atlanta, GA 30307, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9674-6250","authenticated-orcid":false,"given":"Philip N.","family":"Rather","sequence":"additional","affiliation":[{"name":"Research Service, Atlanta VA Medical Center, Decatur, GA 30033, USA"},{"name":"Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30307, USA"},{"name":"Emory Antibiotic Resistance Center, Emory University School of Medicine, Atlanta, GA 30307, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2475067","DOI":"10.1155\/2016\/2475067","article-title":"Mechanisms of Antimicrobial Resistance in ESKAPE Pathogens","volume":"2016","author":"Santajit","year":"2016","journal-title":"Biomed. 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