Abstract
Antimicrobial resistance is a pressing threat to global health, with multidrug-resistant pathogens becoming increasingly prevalent. The bacterial SOS pathway functions in response to DNA damage that occurs during infection, initiating several pro-survival and resistance mechanisms, such as DNA repair and hypermutation. This makes SOS pathway components potential targets that may combat drug-resistant pathogens and decrease resistance emergence. This review discusses the mechanism of the SOS pathway; the structure and function of potential targets AddAB, RecBCD, RecA and LexA; and efforts to develop selective small-molecule inhibitors of these proteins. These inhibitors may serve as valuable tools for target validation and provide the foundations for desperately needed novel antibacterial therapeutics.
Keywords:
SOS response; antimicrobial resistance; drug discovery.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Anti-Bacterial Agents / chemistry*
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Anti-Bacterial Agents / pharmacology
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Bacterial Proteins / antagonists & inhibitors
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Bacterial Proteins / genetics
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DNA Repair / drug effects
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Drug Resistance, Bacterial
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / pharmacology
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Exodeoxyribonuclease V / antagonists & inhibitors
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Exodeoxyribonuclease V / genetics
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Exodeoxyribonucleases / antagonists & inhibitors
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Exodeoxyribonucleases / genetics
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Gene Expression Regulation
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Humans
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Molecular Targeted Therapy
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Rec A Recombinases / antagonists & inhibitors
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Rec A Recombinases / genetics
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SOS Response, Genetics / drug effects*
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Serine Endopeptidases / genetics
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Signal Transduction
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Structure-Activity Relationship
Substances
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Anti-Bacterial Agents
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Bacterial Proteins
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Enzyme Inhibitors
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LexA protein, Bacteria
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Rec A Recombinases
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Exodeoxyribonucleases
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AddAB enzyme
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Exodeoxyribonuclease V
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Serine Endopeptidases