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Potent In Vitro and...
Potent In Vitro and Ex Vivo Anti-Gonococcal Activity of the RpoB Inhibitor Corallopyronin A
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- Edwards, Jennifer L. (author)
- The Center for Microbial Pathogenesis, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA; The Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, USA
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- Balthazar, Jacqueline T. (author)
- Department of Microbiology and Immunology, Emory University School of Medicinegrid.471395.d, Atlanta, Georgia, USA
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- Esposito, Danillo L. A. (author)
- The Center for Microbial Pathogenesis, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA
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- Ayala, Julio C. (author)
- Department of Microbiology and Immunology, Emory University School of Medicinegrid.471395.d, Atlanta, Georgia, USA
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- Schiefer, Andrea (author)
- Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonngrid.15090.3d, Bonn, Germany; German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany
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- Pfarr, Kenneth (author)
- Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonngrid.15090.3d, Bonn, Germany; German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany
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- Hoerauf, Achim (author)
- Institute for Medical Microbiology, Immunology and Parasitology, University Hospital Bonngrid.15090.3d, Bonn, Germany; German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany
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- Alt, Silke (author)
- Translational Project Management Office (TPMO), German Center for Infection Research, Braunschweig, Germany
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- Hesterkamp, Thomas (author)
- Translational Project Management Office (TPMO), German Center for Infection Research, Braunschweig, Germany
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- Grosse, Miriam (author)
- Department Microbial Drugs, Helmholtz Centre for Infection Research, Braunschweig, Germany; German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Braunschweig, Germany
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- Stadler, Marc (author)
- Department Microbial Drugs, Helmholtz Centre for Infection Research, Braunschweig, Germany; German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Braunschweig, Germany
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- Golparian, Daniel, 1984- (author)
- Örebro universitet,Institutionen för medicinska vetenskaper,WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine, Clinical Microbiology
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- Unemo, Magnus, 1970- (author)
- Örebro universitet,Institutionen för medicinska vetenskaper,Region Örebro län,WHO Collaborating Centre for Gonorrhoea and Other STIs, National Reference Laboratory for STIs, Department of Laboratory Medicine, Clinical Microbiology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Institute for Global Health, University College London, London, United Kingdom
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- Read, Timothy D. (author)
- Department of Medicine, Division of Infectious Disease, Emory University School of Medicinegrid.471395.d, Atlanta, Georgia, USA; The Emory Antibiotic Resistance Center, Emory University School of Medicinegrid.471395.d, Atlanta, Georgia, USA
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- Shafer, William M. (author)
- Department of Microbiology and Immunology, Emory University School of Medicinegrid.471395.d, Atlanta, Georgia, USA; The Emory Antibiotic Resistance Center, Emory University School of Medicinegrid.471395.d, Atlanta, Georgia, USA; Laboratories of Bacterial Pathogenesis, Veterans Affairs Medical Center (Atlanta), Decatur, Georgia, USA
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The Center for Microbial Pathogenesis, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA; The Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, USA Department of Microbiology and Immunology, Emory University School of Medicinegrid471395.d, Atlanta, Georgia, USA (creator_code:org_t)
- American Society for Microbiology, 2022
- 2022
- English.
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In: mSphere. - : American Society for Microbiology. - 2379-5042. ; 7:5
- Related links:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Subject headings
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- Gonorrhea remains a major global public health problem because of the high incidence of infection (estimated 82 million cases in 2020) and the emergence and spread of Neisseria gonorrhoeae strains resistant to previous and current antibiotics used to treat infections. Given the dearth of new antibiotics that are likely to enter clinical practice in the near future, there is concern that cases of untreatable gonorrhea might emerge. In response to this crisis, the World Health Organization (WHO), in partnership with the Global Antibiotic Research and Development Partnership (GARDP), has made the search for and development of new antibiotics against N. gonorrhoeae a priority. Ideally, these antibiotics should also be active against other sexually transmitted organisms, such as Chlamydia trachomatis and/or Mycoplasma genitalium, which are often found with N. gonorrhoeae as co-infections. Corallopyronin A is a potent antimicrobial that exhibits activity against Chlamydia spp. and inhibits transcription by binding to the RpoB switch region. Accordingly, we tested the effectiveness of corallopyronin A against N. gonorrhoeae. We also examined the mutation frequency and modes of potential resistance against corallopyronin A. We report that corallopyronin A has potent antimicrobial action against antibiotic-susceptible and antibiotic-resistant N. gonorrhoeae strains and could eradicate gonococcal infection of cultured, primary human cervical epithelial cells. Critically, we found that spontaneous corallopyronin A-resistant mutants of N. gonorrhoeae are exceedingly rare (≤10-10) when selected at 4× the MIC. Our results support pre-clinical studies aimed at developing corallopyronin A for gonorrheal treatment regimens.IMPORTANCE The high global incidence of gonorrhea, the lack of a protective vaccine, and the emergence of N. gonorrhoeae strains expressing resistance to currently used antibiotics demand that new treatment options be developed. Accordingly, we investigated whether corallopyronin A, an antibiotic which is effective against other pathogens, including C. trachomatis, which together with gonococci frequently cause co-infections in humans, could exert anti-gonococcal action in vitro and ex vivo, and potential resistance emergence. We propose that corallopyronin A be considered a potential future treatment option for gonorrhea because of its potent activity, low resistance development, and recent advances in scalable production.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
Keyword
- Neisseria gonorrhoeae
- anti-gonococcal
- biofilm
- corallopyronin A
- ex vivo model
- gonorrhea
Publication and Content Type
- ref (subject category)
- art (subject category)
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Edwards, Jennife ...
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Balthazar, Jacqu ...
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Esposito, Danill ...
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Ayala, Julio C.
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Schiefer, Andrea
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Pfarr, Kenneth
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Hoerauf, Achim
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Alt, Silke
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Hesterkamp, Thom ...
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Grosse, Miriam
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Stadler, Marc
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Golparian, Danie ...
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Unemo, Magnus, 1 ...
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Read, Timothy D.
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Shafer, William ...
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