## 2 QS System in Pseudomonads  
The AHLs-depended QS networks studied are the best so far and the focus of this review will be on the structural basis of that systems in pseudomonads [9]. Moreover, transcriptomic studies have revealed that the AHL-regulated genes and operons constitute over 6% of the genome and are scattered through the chromosome [14; 15]. That supports the view that the AHL system in bacteria constitutes a global regulatory system [16]. AHL signals differ in the chemical structure; the differences are in the length of the acyl chain and the substituents (usually 3-oxo or 3-hydroxy groups) at the 3 position of the acyl chain [17; 18]. In _P. aeruginosa_, two AI synthase genes, _lasl and rhll_, are involved in the synthesis of AHLs; they share significant sequence homologies to _luxl_ of _Vibrio fisheri_[10]. AHLs accumulate both in the cells and in the environment. As the bacteria grow, the concentration of secreted AHL molecules increases [19]. When the population density reaches the \"quorum\", AIs exceed the critical threshold and are recognized by specific receptors that belong to a large class of DNA-binding transcription factors named \"R-proteins\" [18]. In _P. aeruginosa_, the LasR, upon binding to the specific AHL, directly regulates the transcription of target genes by binding to or dissociating from corresponding promoters [10; 18]. Figure 1: Schematic explanation of _Pseudomonas_ spp. adaptation strategies to environmental conditions. In _P. aeruginosa_, there are also two other types of AHL-mediated systems, the _pqs_ system and the _iqs_ system. These networks work in a manner similar to the _las_ and _rhl_ systems, though their AIs are PQS and IQS [20; 21]. PQS is synthesized via a \"head to head\" condensation of anthranilate and \(\beta\)-keto dodecanoate and requires the products of the _pqsA_, _pqsB_, _pqsC_, and _pqsD_ genes, which generate over 50 other 2-alkyl-4-quinolones including 2-heptyl-4-quinolone (HHQ) [22]. Many of these signals are produced at low levels; thus, their biological function is not yet clear [16]. In addition to their regulatory role in the pathogenicity of _P. aeruginosa_, it is believed that PQS can also induce outer membrane vesicle formation, activate the oxidative stress response, act as a stress warning signal, and modulate the host immune response [16; 23; 24]. The role of the last gene of the _pqs_ operon (_pqsE_) is not known, but while _pqsE_ mutants produce parental levels of PQSs, the strains do not exhibit any PQS-related phenotypes; consequently, PqsE is considered to facilitate the response to PQS [25]. The immediate precursors of PQS are HHQ, and its conversion to PQS depends on the activation of PqsH, a putative mono-oxygenase [22] that is LasR regulated, so linking AHL and PQS regulatory networks. IQS belongs to a new class of AIs of the QS system. The genes that are involved in IQS synthesis are a non-ribosomal peptide synthase gene cluster _ambBCDE_. When inhibited, it caused a decrease in the production of PQS and C4-HSL AIs, as well as QS-regulated activities of bacteria [21]. IQS has been shown to contribute to the full virulence of _P. aeruginosa_ in different animal models, highlighting the function of this new QS system in the modulation of bacterial pathogenesis. Importantly, upon phosphate depletion in the culture medium, IQS was demonstrated to be able to partially take over the function of the central _las_ system in pseudomonads [26]. There are interconnections between the aforementioned QS systems in pseudomonads. The _las_ system is activated by 3-oxo-C12-HSL. Next, the LasR-3-oxo-C12-HSL complex multimerizes and stimulates the transcription of _rhlR_, _rhlL_, _lasI_ (hence a positive feedback loop), and other genes that are part of this regulon [27]. The RhlR-C4-HSL also multimerizes and activates its own regulon; _rhl_ forms the second positive feedback loop [10; 28].