Gunnar F Kaufmann1, Junguk Park, Kim D Janda. 1. Skaggs Institute for Chemical Biology, Department of Chemistry and Immunology, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Abstract
BACKGROUND: Cell-to-cell communication via exchange of small molecules, 'autoinducers', is a widespread phenomenon among Gram-negative and -positive bacteria. This intercellular signaling that synchronizes population-wide gene expression in a cell-density-dependent manner is termed 'quorum sensing' (QS). The discovery that Gram-negative bacteria employ non-peptide structures, N-acyl homoserine lactones, to globally regulate production of secondary metabolites and proteins, initiated a new area of research. Subsequently, other quorum-sensing systems and small signaling molecules were identified. With the emergence of antibiotic-resistant bacteria, most prominently methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, new approaches for combating infections are needed. Inhibition of QS results in attenuation of virulence rather than direct killing of microbes. OBJECTIVE: We highlight current trends in preventing bacterial infections using quorum-quenching strategies. METHODS: We mainly focus on P. aeruginosa and S. aureus and their QS systems as targets for intervention. RESULTS/ CONCLUSION: New research strongly suggests that QS systems represent attractive targets for discovery of novel anti-infective agents, including immunotherapeutic strategies.
BACKGROUND: Cell-to-cell communication via exchange of small molecules, 'autoinducers', is a widespread phenomenon among Gram-negative and -positive bacteria. This intercellular signaling that synchronizes population-wide gene expression in a cell-density-dependent manner is termed 'quorum sensing' (QS). The discovery that Gram-negative bacteria employ non-peptide structures, N-acyl homoserine lactones, to globally regulate production of secondary metabolites and proteins, initiated a new area of research. Subsequently, other quorum-sensing systems and small signaling molecules were identified. With the emergence of antibiotic-resistant bacteria, most prominently methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, new approaches for combating infections are needed. Inhibition of QS results in attenuation of virulence rather than direct killing of microbes. OBJECTIVE: We highlight current trends in preventing bacterial infections using quorum-quenching strategies. METHODS: We mainly focus on P. aeruginosa and S. aureus and their QS systems as targets for intervention. RESULTS/ CONCLUSION: New research strongly suggests that QS systems represent attractive targets for discovery of novel anti-infective agents, including immunotherapeutic strategies.
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