Fig. 2

The canonical QS signaling in Gram-positive bacteria and its role in biofilm formation. Agr system was identified as the most classical QS system in Gram-positive bacteria. Agr system in S. aureus, the most common bacteria of Gram-positive bacteria, was well investigated, which are important and responsible for production of virulence factors including toxins and proteases. Agr system is controlled by Agr operon, which includes four elements AgrA, AgrB, AgrC and AgrD. AgrD was the precursor of autoinducer peptides (AIPs), the specific autoinducer in Gram-positive bacteria. AgrD is modified by AgrB and secreted to the extracellular matrix. When the bacteria density become high, AIPs will activate the transmembrane protein AgrC. The phosphorylated AgrC further activates AgrA, finally promoting the target genes expression. There are two promoters which can be regulated by AgrA. One is P2 regulating the Agr proteins and another is P3 which can activate RNAIII expression. RNAIII is the key regulator to modulate the expression of QS-related factors and proteins related to biofilm formation. RNAIII can induce upregulation of virulence factors expression such as proteases, toxins and degradative enzymes. On the other hand, RNAIII can also inhibited the expression of cell adhesive proteins and surface proteins, which might contribute to the bacterial dispersal. These dual functional role of Agr system might balance the bacterial swarming and infection. This will also provide therapeutic targets to develop antibiofilm agents, e.g. targeting AIPs, Agrs or RNAIII