Bacterial quorum sensing: a new target for anti-infective immunotherapy.
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.


CONCLUSIONS
New research strongly suggests that QS systems represent attractive targets for discovery of novel anti-infective agents, including immunotherapeutic strategies.
Kaufmann
Gunnar F
GF
Skaggs Institute for Chemical Biology, Department of Chemistry and Immunology, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Park
Junguk
J
Janda
Kim D
KD
D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000907:Antibodies, Bacterial / Q000276:immunology / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000918:Antibody Specificity; D001419:Bacteria / Q000187:drug effects / Q000276:immunology; D001424:Bacterial Infections / Q000188:drug therapy / Q000628:therapy* / Q000662:veterinary; D001426:Bacterial Proteins / Q000494:pharmacology / Q000502:physiology / Q000627:therapeutic use; D001428:Bacterial Vaccines / Q000627:therapeutic use; D015195:Drug Design; D024881:Drug Resistance, Bacterial; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D006714:Homoserine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology; D006801:Humans; D007116:Immunization, Passive; D007167:Immunotherapy / Q000379:methods*; D016233:Immunotherapy, Active / Q000662:veterinary; D010456:Peptides, Cyclic / Q000037:antagonists & inhibitors / Q000502:physiology; D053038:Quorum Sensing / Q000187:drug effects / Q000502:physiology*; D014774:Virulence
D000900:Anti-Bacterial Agents; D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; C109860:N-(3-oxododecanoyl)homoserine lactone; D010456:Peptides, Cyclic; D006714:Homoserine; D015107:4-Butyrolactone