Fig. 7

Interlinked and mechanistic regulatory network in P. aeruginosa. Interactions between various regulatory systems of P. aeruginosa are linked to regulate adaptation, survival, and resistance to multiple antibiotics, enabling P. aeruginosa to survive environmental stresses. QS systems primarily comprise Las, Rhl, and Pqs and are driven by autoinducer signaling molecules N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12-HSL) N-butanoyl-L-homoserine lactone (C4-HSL), and quinolone signal (PQS) activated through the interaction of transcription factors LasR/RhlR/Pqs and 3-oxo-C12-HSL/C4-HSL/PQS. When signaling molecules reach a putative threshold concentration in the cell environment, QS regulates toxicity expression by regulating two-component systems (TCSs). TCSs regulatory systems, consisting of sensor kinase and response regulator pairs, play roles in bacterial adaptation by regulating the expression of a variety of extracellular enzymes, virulence factors, and QS molecules. GacS/GacA TCS is regulated by sensor kinases RetS (positive regulation) and LadS (negative regulation). Transcription of non-coding regulatory RNAs of the RsmY/Z depends on the activation of GacS/GacA to activate RsmA and regulate the T3SS-mediated virulence secretion and biofilm formation. Biofilms are encapsulated in a self-generating extracellular polymer (EPS) matrix for species survival in surprising alterations of living conditions, like temperature fluctuations and nutrient availability, especially the antibiotic threat. Likewise, the secretory system activates the host immune response through virulence factors. TLRs play a key role in innate immunity. TLR1, 2, 4, 5, 6, and 9 are reported for recognizing P. aeruginosa infection and mediating inflammatory response signal pathways. T3SS and bacterial QS-dependent secretants have roles in modulating NLRP3 and NLRC4 inflammasome activation under P. aeruginosa challenge