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Antibacterial Mechanisms and Efficacy of Sarecycline in Animal Models of Infection and Inflammation

Prolonged broad-spectrum antibiotic use is more likely to induce bacterial resistance and dysbiosis of skin and gut microflora. First and second-generation tetracycline-class antibiotics have similar broad-spectrum antibacterial activity. Targeted tetracycline-class antibiotics are needed to limit a...

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Autores principales: Bunick, Christopher G., Keri, Jonette, Tanaka, S. Ken, Furey, Nika, Damiani, Giovanni, Johnson, Jodi L., Grada, Ayman
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071131/
https://www.ncbi.nlm.nih.gov/pubmed/33920812
http://dx.doi.org/10.3390/antibiotics10040439
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author Bunick, Christopher G.
Keri, Jonette
Tanaka, S. Ken
Furey, Nika
Damiani, Giovanni
Johnson, Jodi L.
Grada, Ayman
author_facet Bunick, Christopher G.
Keri, Jonette
Tanaka, S. Ken
Furey, Nika
Damiani, Giovanni
Johnson, Jodi L.
Grada, Ayman
author_sort Bunick, Christopher G.
collection PubMed
description Prolonged broad-spectrum antibiotic use is more likely to induce bacterial resistance and dysbiosis of skin and gut microflora. First and second-generation tetracycline-class antibiotics have similar broad-spectrum antibacterial activity. Targeted tetracycline-class antibiotics are needed to limit antimicrobial resistance and improve patient outcomes. Sarecycline is a narrow-spectrum, third-generation tetracycline-class antibiotic Food and Drug Administration (FDA)-approved for treating moderate-to-severe acne. In vitro studies demonstrated activity against clinically relevant Gram-positive bacteria but reduced activity against Gram-negative bacteria. Recent studies have provided insight into how the structure of sarecycline, with a unique C7 moiety, interacts with bacterial ribosomes to block translation and prevent antibiotic resistance. Sarecycline reduces Staphylococcus aureus DNA and protein synthesis with limited effects on RNA, lipid, and bacterial wall synthesis. In agreement with in vitro data, sarecycline demonstrated narrower-spectrum in vivo activity in murine models of infection, exhibiting activity against S. aureus, but reduced efficacy against Escherichia coli compared to doxycycline and minocycline. In a murine neutropenic thigh wound infection model, sarecycline was as effective as doxycycline against S. aureus. The anti-inflammatory activity of sarecycline was comparable to doxycycline and minocycline in a rat paw edema model. Here, we review the antibacterial mechanisms of sarecycline and report results of in vivo studies of infection and inflammation.
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spelling pubmed-80711312021-04-26 Antibacterial Mechanisms and Efficacy of Sarecycline in Animal Models of Infection and Inflammation Bunick, Christopher G. Keri, Jonette Tanaka, S. Ken Furey, Nika Damiani, Giovanni Johnson, Jodi L. Grada, Ayman Antibiotics (Basel) Review Prolonged broad-spectrum antibiotic use is more likely to induce bacterial resistance and dysbiosis of skin and gut microflora. First and second-generation tetracycline-class antibiotics have similar broad-spectrum antibacterial activity. Targeted tetracycline-class antibiotics are needed to limit antimicrobial resistance and improve patient outcomes. Sarecycline is a narrow-spectrum, third-generation tetracycline-class antibiotic Food and Drug Administration (FDA)-approved for treating moderate-to-severe acne. In vitro studies demonstrated activity against clinically relevant Gram-positive bacteria but reduced activity against Gram-negative bacteria. Recent studies have provided insight into how the structure of sarecycline, with a unique C7 moiety, interacts with bacterial ribosomes to block translation and prevent antibiotic resistance. Sarecycline reduces Staphylococcus aureus DNA and protein synthesis with limited effects on RNA, lipid, and bacterial wall synthesis. In agreement with in vitro data, sarecycline demonstrated narrower-spectrum in vivo activity in murine models of infection, exhibiting activity against S. aureus, but reduced efficacy against Escherichia coli compared to doxycycline and minocycline. In a murine neutropenic thigh wound infection model, sarecycline was as effective as doxycycline against S. aureus. The anti-inflammatory activity of sarecycline was comparable to doxycycline and minocycline in a rat paw edema model. Here, we review the antibacterial mechanisms of sarecycline and report results of in vivo studies of infection and inflammation. MDPI 2021-04-15 /pmc/articles/PMC8071131/ /pubmed/33920812 http://dx.doi.org/10.3390/antibiotics10040439 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Bunick, Christopher G.
Keri, Jonette
Tanaka, S. Ken
Furey, Nika
Damiani, Giovanni
Johnson, Jodi L.
Grada, Ayman
Antibacterial Mechanisms and Efficacy of Sarecycline in Animal Models of Infection and Inflammation
title Antibacterial Mechanisms and Efficacy of Sarecycline in Animal Models of Infection and Inflammation
title_full Antibacterial Mechanisms and Efficacy of Sarecycline in Animal Models of Infection and Inflammation
title_fullStr Antibacterial Mechanisms and Efficacy of Sarecycline in Animal Models of Infection and Inflammation
title_full_unstemmed Antibacterial Mechanisms and Efficacy of Sarecycline in Animal Models of Infection and Inflammation
title_short Antibacterial Mechanisms and Efficacy of Sarecycline in Animal Models of Infection and Inflammation
title_sort antibacterial mechanisms and efficacy of sarecycline in animal models of infection and inflammation
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071131/
https://www.ncbi.nlm.nih.gov/pubmed/33920812
http://dx.doi.org/10.3390/antibiotics10040439
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