## 1 Introduction
Mature proteases promote a proteolytic effect in tissues, leading to proinflammatory cytokines production and enhancing the inflammatory host response [14]. [PERSON] et al. achieved the inhibition of the QS using isolated plant compounds, such as trans-cinnamaldehyde (CA) and salicylic acid (SA). In their study, both compounds achieved a downregulation of _las_ and _rhl_ within the QS, and the CA achieved a reduction of 13-fold in _las_ and 7-fold in _rhl_. Additionally, the compounds reduced the production of extracellular virulence factors such as proteases by 65%, elastases by 22%, and pyocyanins by 32% [12]. Pyocyanins are another produced PAO1 virulence trait. Pyocyanins are a blue phenazine pigment with antioxidant capacity produced by 90 to 95% of PAO1 strains [15]. Therefore, pyocyanins confer a protective mechanism against the reactive oxygen species (ROS) produced by the immune system of the host by the inactivation of catalases [1]. Rhamonolipids are another example of a PAO1 virulence trait. Rhamonolipids are made up of glycolipids, biosurfactants, and phenazines, which are components of the biofilm matrix and have extracellular redox activity. Additionally, rhamnols can cause the lysis of polymorphonuclear cells and macrophages [14]. [PERSON] et al. perceived that the compound paenol, a phenolic compound, could significantly downregulate the transcription of the QS-related genes in PAO1, _lasl/R_, _rhl/R_, and _pgs/mvf_. In their study, paenol could significantly inhibit rhamnpid production by 66.27% after 24 h [16]. Figure 1: Operons and genes involved on the expression of the different _Pseudomonas aeruginosa_ virulence factors in the quorum sensing system. The genes and operons have been summarized by arrows and boxes, and the virulent traits influenced by each are described alongside (in parentheses). Created by the authors using BioRender.com (accessed on 11 August 2022). The resistance of _P. aeruginosa_ strains can also be affected by interfering with the specific gene of each metabolic pathway. For example, \(rubA2\), and \(rubA1\) are two genes encoded by the cluster \(rubB\) that are related to the expression of the rubredoxins reductases (Rdxs). Rdxs are redox-active iron-sulfur proteins crucial for the reduction of oxygen species produced by the host, and, consequently, for the survival of the bacteria during infection [17]. In _P. aeruginosa_, the Rdxs are necessary for the growth on alkanes. The Rdxs are found upregulated in several highly virulent mutant strains. The Rdxs are considered essential for survival and proliferation after the phagocytosis process of the host defenses. Additionally, the mutant strain in Rdxs have a very impaired QS and exhibited lower virulence in animal infection models [18]. Another example is the glutaredoxin (GLRX) gene. The GLRX gene codifies small ubiquitous redox enzymes; these enzymes catalyze the reduction of thiol-dissulfide exchange reactions dependent on glutathione. A study performed with a grxD mutant demonstrated reduced virulence in _Drosophila melanogaster_[19]. Additionally, GLRX has a protective effect against antibiotic drugs [20]. To control bacterial infections, an alternative method against antibiotic drug-resistant bacteria is phage therapy. Phages are viruses that infect specific strains of bacteria. This specificity contrasts with antibiotics, which display a more general specer of bacterial strains [21]. Phage therapy uses lytic phages, phages whose infection results in the lyse of bacteria, that are able to penetrate difficult environments such as biofilms. Phages are usually used in cocktails, where more than one phage type is used. Phages encode a polysaccharide hydrolase that has the ability to adsorb, invade, and shatter the bacterial host [21]. Phage therapy is useful in many sectors, including agriculture, to control plant bacterial infections [22], multi-drug resistant microorganisms in humans and animals, and in research, where phages have been studied for the treatment of bacterial infections in in vitro and in vivo models [23].