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Evaluation of analogs of mutacin 1140 in systemic and cutaneous methicillin-resistant Staphylococcus aureus infection models in mice

Mutacin 1140 (Mu1140) is a potent antibiotic against Gram-positive bacteria, such as Staphylococcus aureus. The antibiotic is produced by the oral bacterium Streptococcus mutans and is a member of the epidermin family of type AI lantibiotics. The antibiotic exerts its inhibitory activity by binding...

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Autores principales: Ju, Min, Joseph, Thushinari, Hansanant, Nopakorn, Geng, Mengxin, Williams, McKinley, Cothrell, Andrew, Buhrow, Andrew Riley, Austin, Frank, Smith, Leif
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9794991/
https://www.ncbi.nlm.nih.gov/pubmed/36590413
http://dx.doi.org/10.3389/fmicb.2022.1067410
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author Ju, Min
Joseph, Thushinari
Hansanant, Nopakorn
Geng, Mengxin
Williams, McKinley
Cothrell, Andrew
Buhrow, Andrew Riley
Austin, Frank
Smith, Leif
author_facet Ju, Min
Joseph, Thushinari
Hansanant, Nopakorn
Geng, Mengxin
Williams, McKinley
Cothrell, Andrew
Buhrow, Andrew Riley
Austin, Frank
Smith, Leif
author_sort Ju, Min
collection PubMed
description Mutacin 1140 (Mu1140) is a potent antibiotic against Gram-positive bacteria, such as Staphylococcus aureus. The antibiotic is produced by the oral bacterium Streptococcus mutans and is a member of the epidermin family of type AI lantibiotics. The antibiotic exerts its inhibitory activity by binding to the cell wall precursor lipid II, blocking cell wall synthesis, and by disrupting bacterial membranes. In previous studies, the novel K2A and R13A analogs of Mu1140 have been identified to have superior pharmacokinetic properties compared to native Mu1140. In this study, the use of a combined formulation of the Mu1140 K2A and R13A analogs was shown to be more effective at treating MRSA bacteremia than the native Mu1140 or vancomycin. The analogs were also shown to be effective in treating an MRSA skin infection. The use of K2A and R13A analogs may provide a future alternative for treating serious Gram-positive bacterial infections. In a previous study, the Mu1140 analogs were shown to have significantly longer drug clearance times, leading to higher plasma concentrations over time. These properties warranted further testing to determine whether the analogs are effective for the treatment of systemic MRSA and acute skin infections. In this study, Mu1140 analogs were shown to be more effective than currently available treatments for systemic and skin MRSA infections. Further, the study clearly shows that the new analogs are superior to native Mu1140 for the treatment of a systemic MRSA infection. These findings support continued drug product development efforts using the K2A and R13A Mu1140 analogs, and that these analogs may ameliorate the outcome of serious bacterial infections.
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spelling pubmed-97949912022-12-29 Evaluation of analogs of mutacin 1140 in systemic and cutaneous methicillin-resistant Staphylococcus aureus infection models in mice Ju, Min Joseph, Thushinari Hansanant, Nopakorn Geng, Mengxin Williams, McKinley Cothrell, Andrew Buhrow, Andrew Riley Austin, Frank Smith, Leif Front Microbiol Microbiology Mutacin 1140 (Mu1140) is a potent antibiotic against Gram-positive bacteria, such as Staphylococcus aureus. The antibiotic is produced by the oral bacterium Streptococcus mutans and is a member of the epidermin family of type AI lantibiotics. The antibiotic exerts its inhibitory activity by binding to the cell wall precursor lipid II, blocking cell wall synthesis, and by disrupting bacterial membranes. In previous studies, the novel K2A and R13A analogs of Mu1140 have been identified to have superior pharmacokinetic properties compared to native Mu1140. In this study, the use of a combined formulation of the Mu1140 K2A and R13A analogs was shown to be more effective at treating MRSA bacteremia than the native Mu1140 or vancomycin. The analogs were also shown to be effective in treating an MRSA skin infection. The use of K2A and R13A analogs may provide a future alternative for treating serious Gram-positive bacterial infections. In a previous study, the Mu1140 analogs were shown to have significantly longer drug clearance times, leading to higher plasma concentrations over time. These properties warranted further testing to determine whether the analogs are effective for the treatment of systemic MRSA and acute skin infections. In this study, Mu1140 analogs were shown to be more effective than currently available treatments for systemic and skin MRSA infections. Further, the study clearly shows that the new analogs are superior to native Mu1140 for the treatment of a systemic MRSA infection. These findings support continued drug product development efforts using the K2A and R13A Mu1140 analogs, and that these analogs may ameliorate the outcome of serious bacterial infections. Frontiers Media S.A. 2022-12-14 /pmc/articles/PMC9794991/ /pubmed/36590413 http://dx.doi.org/10.3389/fmicb.2022.1067410 Text en Copyright © 2022 Ju, Joseph, Hansanant, Geng, Williams, Cothrell, Buhrow, Austin and Smith. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Ju, Min
Joseph, Thushinari
Hansanant, Nopakorn
Geng, Mengxin
Williams, McKinley
Cothrell, Andrew
Buhrow, Andrew Riley
Austin, Frank
Smith, Leif
Evaluation of analogs of mutacin 1140 in systemic and cutaneous methicillin-resistant Staphylococcus aureus infection models in mice
title Evaluation of analogs of mutacin 1140 in systemic and cutaneous methicillin-resistant Staphylococcus aureus infection models in mice
title_full Evaluation of analogs of mutacin 1140 in systemic and cutaneous methicillin-resistant Staphylococcus aureus infection models in mice
title_fullStr Evaluation of analogs of mutacin 1140 in systemic and cutaneous methicillin-resistant Staphylococcus aureus infection models in mice
title_full_unstemmed Evaluation of analogs of mutacin 1140 in systemic and cutaneous methicillin-resistant Staphylococcus aureus infection models in mice
title_short Evaluation of analogs of mutacin 1140 in systemic and cutaneous methicillin-resistant Staphylococcus aureus infection models in mice
title_sort evaluation of analogs of mutacin 1140 in systemic and cutaneous methicillin-resistant staphylococcus aureus infection models in mice
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9794991/
https://www.ncbi.nlm.nih.gov/pubmed/36590413
http://dx.doi.org/10.3389/fmicb.2022.1067410
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