In vitro antibacterial effects of statins against bacterial pathogens causing skin infections

With financial considerations impeding research and development of new antibiotics, drug repurposing (finding new indications for old drugs) emerges as a feasible alternative. Statins are extensively prescribed around the world to lower cholesterol, but they also possess inherent antimicrobial prope...

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Published inEuropean journal of clinical microbiology & infectious diseases Vol. 37; no. 6; pp. 1125 - 1135
Main Authors Ko, Humphrey H. T., Lareu, Ricky R., Dix, Brett R., Hughes, Jeffery D.
Format Journal Article
LanguageEnglish
Published Berlin/Heidelberg Springer Berlin Heidelberg 01.06.2018
Springer Nature B.V
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Abstract With financial considerations impeding research and development of new antibiotics, drug repurposing (finding new indications for old drugs) emerges as a feasible alternative. Statins are extensively prescribed around the world to lower cholesterol, but they also possess inherent antimicrobial properties. This study identifies statins with the greatest potential to be repurposed as topical antibiotics and postulates a mechanism of action for statins’ antibacterial activity. Using broth microdilution, the direct antibacterial effects of all seven parent statins currently registered for human use and three selected statin metabolites were tested against bacterial skin pathogens Staphylococcus aureus , Escherichia coli , Pseudomonas aeruginosa , and Serratia marcescens . Simvastatin and pitavastatin lactone exerted the greatest antibacterial effects (minimum inhibitory concentrations of 64 and 128 μg/mL, respectively) against S. aureus. None of the statins tested were effective against E. coli , P. aeruginosa , or S. marcescens , but simvastatin hydroxy acid acid might be active against S. aureus , E. coli , and S. marcescens at drug concentrations > 256 μg/mL . It was found that S. aureus may exhibit a paradoxical growth effect when exposed to simvastatin; thus, treatment failure at high drug concentrations is theoretically probable. Through structure-activity relationship analysis, we postulate that statins’ antibacterial action may involve disrupting the teichoic acid structures or decreasing the number of alanine residues present on Gram-positive bacterial cell surfaces, which could reduce biofilm formation, diminish bacterial adhesion to environmental surfaces, or impede S. aureus cell division.
AbstractList With financial considerations impeding research and development of new antibiotics, drug repurposing (finding new indications for old drugs) emerges as a feasible alternative. Statins are extensively prescribed around the world to lower cholesterol, but they also possess inherent antimicrobial properties. This study identifies statins with the greatest potential to be repurposed as topical antibiotics and postulates a mechanism of action for statins' antibacterial activity. Using broth microdilution, the direct antibacterial effects of all seven parent statins currently registered for human use and three selected statin metabolites were tested against bacterial skin pathogens Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Serratia marcescens. Simvastatin and pitavastatin lactone exerted the greatest antibacterial effects (minimum inhibitory concentrations of 64 and 128 μg/mL, respectively) against S. aureus. None of the statins tested were effective against E. coli, P. aeruginosa, or S. marcescens, but simvastatin hydroxy acid acid might be active against S. aureus, E. coli, and S. marcescens at drug concentrations > 256 μg/mL. It was found that S. aureus may exhibit a paradoxical growth effect when exposed to simvastatin; thus, treatment failure at high drug concentrations is theoretically probable. Through structure-activity relationship analysis, we postulate that statins' antibacterial action may involve disrupting the teichoic acid structures or decreasing the number of alanine residues present on Gram-positive bacterial cell surfaces, which could reduce biofilm formation, diminish bacterial adhesion to environmental surfaces, or impede S. aureus cell division.
With financial considerations impeding research and development of new antibiotics, drug repurposing (finding new indications for old drugs) emerges as a feasible alternative. Statins are extensively prescribed around the world to lower cholesterol, but they also possess inherent antimicrobial properties. This study identifies statins with the greatest potential to be repurposed as topical antibiotics and postulates a mechanism of action for statins’ antibacterial activity. Using broth microdilution, the direct antibacterial effects of all seven parent statins currently registered for human use and three selected statin metabolites were tested against bacterial skin pathogens Staphylococcus aureus , Escherichia coli , Pseudomonas aeruginosa , and Serratia marcescens . Simvastatin and pitavastatin lactone exerted the greatest antibacterial effects (minimum inhibitory concentrations of 64 and 128 μg/mL, respectively) against S. aureus. None of the statins tested were effective against E. coli , P. aeruginosa , or S. marcescens , but simvastatin hydroxy acid acid might be active against S. aureus , E. coli , and S. marcescens at drug concentrations > 256 μg/mL . It was found that S. aureus may exhibit a paradoxical growth effect when exposed to simvastatin; thus, treatment failure at high drug concentrations is theoretically probable. Through structure-activity relationship analysis, we postulate that statins’ antibacterial action may involve disrupting the teichoic acid structures or decreasing the number of alanine residues present on Gram-positive bacterial cell surfaces, which could reduce biofilm formation, diminish bacterial adhesion to environmental surfaces, or impede S. aureus cell division.
With financial considerations impeding research and development of new antibiotics, drug repurposing (finding new indications for old drugs) emerges as a feasible alternative. Statins are extensively prescribed around the world to lower cholesterol, but they also possess inherent antimicrobial properties. This study identifies statins with the greatest potential to be repurposed as topical antibiotics and postulates a mechanism of action for statins’ antibacterial activity. Using broth microdilution, the direct antibacterial effects of all seven parent statins currently registered for human use and three selected statin metabolites were tested against bacterial skin pathogens Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Serratia marcescens. Simvastatin and pitavastatin lactone exerted the greatest antibacterial effects (minimum inhibitory concentrations of 64 and 128 μg/mL, respectively) against S. aureus. None of the statins tested were effective against E. coli, P. aeruginosa, or S. marcescens, but simvastatin hydroxy acid acid might be active against S. aureus, E. coli, and S. marcescens at drug concentrations > 256 μg/mL. It was found that S. aureus may exhibit a paradoxical growth effect when exposed to simvastatin; thus, treatment failure at high drug concentrations is theoretically probable. Through structure-activity relationship analysis, we postulate that statins’ antibacterial action may involve disrupting the teichoic acid structures or decreasing the number of alanine residues present on Gram-positive bacterial cell surfaces, which could reduce biofilm formation, diminish bacterial adhesion to environmental surfaces, or impede S. aureus cell division.
With financial considerations impeding research and development of new antibiotics, drug repurposing (finding new indications for old drugs) emerges as a feasible alternative. Statins are extensively prescribed around the world to lower cholesterol, but they also possess inherent antimicrobial properties. This study identifies statins with the greatest potential to be repurposed as topical antibiotics and postulates a mechanism of action for statins' antibacterial activity. Using broth microdilution, the direct antibacterial effects of all seven parent statins currently registered for human use and three selected statin metabolites were tested against bacterial skin pathogens Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Serratia marcescens. Simvastatin and pitavastatin lactone exerted the greatest antibacterial effects (minimum inhibitory concentrations of 64 and 128 μg/mL, respectively) against S. aureus. None of the statins tested were effective against E. coli, P. aeruginosa, or S. marcescens, but simvastatin hydroxy acid acid might be active against S. aureus, E. coli, and S. marcescens at drug concentrations > 256 μg/mL. It was found that S. aureus may exhibit a paradoxical growth effect when exposed to simvastatin; thus, treatment failure at high drug concentrations is theoretically probable. Through structure-activity relationship analysis, we postulate that statins' antibacterial action may involve disrupting the teichoic acid structures or decreasing the number of alanine residues present on Gram-positive bacterial cell surfaces, which could reduce biofilm formation, diminish bacterial adhesion to environmental surfaces, or impede S. aureus cell division.
Author Lareu, Ricky R.
Ko, Humphrey H. T.
Dix, Brett R.
Hughes, Jeffery D.
Author_xml – sequence: 1
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  surname: Ko
  fullname: Ko, Humphrey H. T.
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  givenname: Ricky R.
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  fullname: Lareu, Ricky R.
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  fullname: Dix, Brett R.
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  givenname: Jeffery D.
  surname: Hughes
  fullname: Hughes, Jeffery D.
  organization: School of Pharmacy and Biomedical Sciences, Faculty of Health Sciences, Curtin University
BackLink https://www.ncbi.nlm.nih.gov/pubmed/29569046$$D View this record in MEDLINE/PubMed
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Keywords Drug repurposing
Skin infections
Mechanism of action
Topical antibiotics
Statins
Paradoxical growth effect
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PublicationTitle European journal of clinical microbiology & infectious diseases
PublicationTitleAbbrev Eur J Clin Microbiol Infect Dis
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PublicationYear 2018
Publisher Springer Berlin Heidelberg
Springer Nature B.V
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Snippet With financial considerations impeding research and development of new antibiotics, drug repurposing (finding new indications for old drugs) emerges as a...
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SubjectTerms Alanine
Anti-Bacterial Agents - chemistry
Anti-Bacterial Agents - pharmacology
Anti-Infective Agents, Local - pharmacology
Antibacterial activity
Antibiotics
Bacteria
Biofilms
Biomedical and Life Sciences
Biomedicine
Cell division
Cholesterol
Drug development
Drug Discovery
Drug Repositioning
E coli
Escherichia coli - drug effects
Escherichia coli - pathogenicity
Failure analysis
Gram-Negative Bacteria - drug effects
Gram-Positive Bacteria - drug effects
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology
Internal Medicine
Medical Microbiology
Metabolites
Microbial Sensitivity Tests
Original Article
Pathogens
Pseudomonas aeruginosa
Pseudomonas aeruginosa - drug effects
Pseudomonas aeruginosa - pathogenicity
R&D
Research & development
Simvastatin
Simvastatin - analogs & derivatives
Simvastatin - pharmacology
Skin
Skin - microbiology
Skin tests
Staphylococcal Skin Infections - drug therapy
Staphylococcal Skin Infections - microbiology
Staphylococcus aureus - drug effects
Staphylococcus aureus - pathogenicity
Statins
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Title In vitro antibacterial effects of statins against bacterial pathogens causing skin infections
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