AIP-II – Immunology – Antigens/Epitotes/Pools/Librairies

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. AIP-II has the conserved thiolactone macrocycle of the AIP family. Asn-3, Leu-8, and Phe-9 have been shown to be critical for activation of the agr response while inhibition relies on Leu-8 and Phe-9. The reactive thiol ester bond is only necessary for activation of the agr response. Further work may provide further AIP:AgrC inhibitors.