Abstract
Staphylococcus aureus is the leading cause of hospital-acquired infections. The enzyme sortase A, present on the cell surface of S. aureus, plays a key role in bacterial virulence without affecting the bacterial viability. Inhibition of sortase A activity offers a powerful but clinically less explored therapeutic strategy, as it offers the possibility of not inducing any selective pressure on the bacteria to evolve drug-resistant strains. In this Perspective, we offer a chemical space narrative for the design of sortase A inhibitors, as delineated into three broad domains: peptidomimetics, natural products, and synthetic small molecules. This provides immense opportunities for medicinal chemists to alleviate the ever-growing crisis of antibiotic resistance.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aminoacyltransferases / antagonists & inhibitors*
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Aminoacyltransferases / metabolism
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Animals
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Anti-Bacterial Agents / chemistry
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Anti-Bacterial Agents / metabolism
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Anti-Bacterial Agents / pharmacology*
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Bacterial Proteins / antagonists & inhibitors*
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Bacterial Proteins / metabolism
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Cell Line
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Cysteine Endopeptidases / metabolism
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Cysteine Proteinase Inhibitors / chemistry
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Cysteine Proteinase Inhibitors / metabolism
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Cysteine Proteinase Inhibitors / pharmacology*
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Humans
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Molecular Docking Simulation
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Protein Binding
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Staphylococcus aureus / drug effects
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Virulence / drug effects
Substances
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Anti-Bacterial Agents
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Bacterial Proteins
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Cysteine Proteinase Inhibitors
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Aminoacyltransferases
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sortase A
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Cysteine Endopeptidases