# Genomic and Metabolic Characteristics of the Pathogenicity in Pseudomonas aeruginosa
## 4 Metabolic Pathways Associated with Pathogenicity
### Virulence Factors  
#### 4.1.1 Secretion Systems  
_P. aeruginosa_ possesses a series of complex secretion systems, which deliver virulence factors such as toxins, elastases, lipases, and proteases, either to the extracellular environment or within the cytosol of the host cell [52]. _P. aeruginosa_ contains five secretion systems: type I, type II, type III, type V and type VI (Figure 2) [53]. Type I secretion system (T1 SS) is one of the simplest bacterial secretion systems described to date. T1 SS require three components: an outer membrane (OM) protein, an ABC (ATP-binding cassette) transporter, which is inserted in the inner membrane (IM) and provides energy to the transport process, and an adaptor protein connecting these two components in the periplasm [54]. In _P. aeruginosa_, two types of T1 SS exist. One of these types is the HasAp system, that consists of an ABC transporter (HasD), adaptor (HasE), and OMF (HasF) [52; 54]. The HasAp protein is a hemophore, with the ability to bind heme from hemoglobin. This protein is considered crucial component for the survival of _P. aeruginosa_ and is especially important during the early stages of infection, where iron is scarce, as it can allow the acquisition of heme iron from hemoglobin [54]. The other type of T1 SS is the Apr system, which involves an ABC transporter (AprD), adaptor (AprE), and OMF (AprF), and is implicated in the extracellular secretion of the alkaline protease AprA and of AprX [54; 55], which is a virulence factor involved in various infections caused by this bacterium [56]. Type II secretion system (T2 SS) is a very versatile system. Being widely preserved in Gram-negative bacteria, its sole purpose is to promote the transport of large multimeric proteins, previously folded in the periplasm, by the outer membrane [57]. T2 SS uses a two-stage process for the delivery of extracellular proteins: the first one involves the Sec- or Tat-dependent delivery from the cytoplasm into the periplasm, and the second stage involves T2 SS complex-mediated further secretion into the extracellular space [58]. In _P. aeruginosa_, there are two different T2 SS types: the Xcp (extracellular protein) system can secrete at least 14 proteins with different functions, such as proteases and lipases, and the Hxc (homologous to Xcp) system, only functional in phosphate-limiting growth conditions [59].The latter system can only secrete one protein, LapA, an alkaline phosphatase. The Xcp system is encoded by 11 genes organized into two divergent operons, xcpP to Q and xcpR to Z. Moreover, there is a 12 th gene, xcpA/pilD, located beyond the 2 xcp operons [53; 60]. Some examples of secreted proteins include elastase (LasB, LasA), phospholipases, and lipases (PlcN, PlcH, LipA and LipC), as well as exotoxin A (ToxA), all of which playing major roles during infection. Elastase leads to the degradation of the connective tissue in the lungs, which is mainly composed of elastin [61]. Also affecting the pulmonary system, phospholipases and lipases degrade surfactants and modify immune function in these organs [62; 63]. On the other hand, exotoxin A is one of the most important virulence factors in _P. aeruginosa_, because it inhibits protein synthesis by ADP-ribosylation of cell elongation factor-2 in the host cell, consequently leading to cell death [64]. A study carried out by [PERSON] and his collaborators demonstrated that samples of _P. aeruginosa_ in hospital wastewater harbored virulence traits through the identification of genes that conferred this virulence on them, such as _popB_, _lasB_, _lasA and toxA_. This demonstrates a serious public health problem since these virulence factors can stimulate the adaptability of these bacteria to the environment and exert pathogenicity on the susceptible host [65]. The type III secretion system (T3 SS) forms a needle complex which allows the injection of effector proteins from the bacterial cytosol to the extracellular environment [4], and is also related to the flagellar assembly machine [53].