Staphylococcus aureus is a major human pathogen that utilizes autoinducing peptide (AIP) signals to regulate virulence. Methods to intercept bacterial quorum sensing (QS) aim to find novel anti-virulence treatments.

Auto-inducing peptide (AIP) is a cyclic thiolactone quorum sensing peptide from Staphylococcus aureus which is responsible for activating the agr response. AIP is released from the bacteria and its extracellular concentration is then sensed by a two-component system on the bacterial surface, AgrC and AgrA. AgrC is the membrane histidine kinase receptor and AgrA is a response regulator; upon binding of AIP, AgrC phosphorylates AgrA.

AIP accumulates during growth activating an AgrC and AgrA cascade when it reaches a critical signal level. This cascade activates P2 and P3 promoters which autoactivate the agr system and upregulate RNAIII transcription. RNAIII regulates the expression of virulence factors including toxins, super-antigens, and exo-enzymes. Extensive research to identify AIP:AgrC inhibitors aims to find therapeutics against pathogens.

AgrD is the precursor peptide of AIP, and AgrB is an integral membrane endopeptidase essential to biosynthesize AIP. This AIP system is conserved among many Gram-positive bacteria. S. aureus strains are categorized into four groups (I–IV) according to their AIP signal and cognate extracellular receptor, AgrC. Each group is associated with a certain disease profile,  S. aureus group-IV strains have been associated with generalized exfoliative syndromes and osteoarticular infections.  AIP-IV has been used to develop antibodies and an effective ELISA help detect AIP-IV levels in the nanomolar range. This can be implemented to identify S. aureus type IV infections in patient samples.