# _Legionella pneumophila_--Virulence Factors and the Possibility of Infection in Dental Practice
## 3 Virulence Factors
### Secreted Factors  
_Legionella_ spp. secretes various pigments, toxins, and enzymes [58]. Moreover, _Legionella_ spp. secretes more than 18,000 proteins containing eukaryotic-like domains, calledeffector proteins, through secretion systems [13]. Many effector proteins are secreted into the host cell, facilitating _Legionella_ intracellular replication [13]. These secretion systems are essential virulence factors in _L. pneumoniae_.  
The type I secretion system known as Lss consists of the ABC transporter (ATP-binding cassette), a membrane-fusion protein, and an outer-membrane protein [59]. The _lss_ gene cluster, _lssXYZABD_, which includes the ABC transporter and membrane fusion protein, was found in all _L. pneumoniae_ strains [50].  
Secretion system type II, termed Lsp and often referred to as the general secretory pathway, contains numerous degradation enzymes, including RNase, two acid phosphatases, zinc metalloprotease, etc. [60; 61]. The _L. pneumoniae_ type II secretion system has 12 components. Some components are the prepilin peptidase _piiD_, the outer membrane secretion and ATPase _lspDE_, and the pseudopilins _lspFGHIJK_, _lspC_, and _lspLM_[57]. The Lsp secretion system is essential for _L. pneumoniae_ survival at low temperatures [50].  
The type III secretion system is a protein-transport mechanism that translocates cytoplasmic substrates directly into the host cytoplasm [62]. It contains flagellum-encoding genes [59] and secretins as part of a type II secretion system, homologous to the DotD protein in a type IVB secretion system [63].  
Another important secretory system is the type IV secretory system. There are two subclasses of the type IV system--IVA (called Lvh) and IVB (called Dot (defect in organelle trafficking) /Icm (intracellular multiplication)) [59]. The Dot/Icm secretory system is encoded by the _Dot/Icm_ genes [63]. The Dot/Icm secretion system secretes more than 300 different effector proteins into the host cell and is crucial for the virulence of _L. pneumoniae_[13]. Therefore, the Dot/Icm secretion system constitutes around 10% of the _L. pneumoniae_ proteome, suggesting that the effectors include a significant determinant of _L. pneumoniae_ survival [50]. The Dot/Icm system is vital for establishing a replicator niche and avoiding lysosomal/endocytic fusion [64]. The action of bacterial degradation enzymes ultimately leads to the death and lysis of host cells and damage to lung tissue [65; 66]. In addition, the Dot/Icm effector proteins are required to translocate the _Legionella_-containing vacuole across the membrane [23]. The Lvh secretion system contains genes encoding mobility factors and enzymes [59]. It may have a role during intracellular replication of _L. pneumoniae_ and thus complement Dot/Icm function [50]. In addition, the Lvh can functionally replace defective Dot/Icm [67].  
Type II and IVB secretion systems are found in all _Legionella_ strains, while the type I secretion system is exclusive for _L. pneumoniae_[65]. In addition, type II and IVA secretion systems are found in some _Legionella_ strains [59]. However, some effector proteins of type II, III, and IVA secretion systems are homologous to the components of the type IVB secretion system, and are therefore not found in all _Legionella_ strains [63]. Secretory systems are essential for virulence, and _Legionella_ species that have additional secretory systems have increased pathogenicity [59].  
The brown pigment, or pyomelanin, is one of the frequently studied secreted factors. It is a polymer formed with homogenate acid (HGA), produced by bacteria with oxygen [68]. The _lly_ gene is necessary for its formation [69]. Mutagenesis of _Lly_ gene does not affect intracellular replication within amoebae or macrophage-like host cells [69]. Secreted HGA becomes toxic in the presence of oxygen [70]. Pyomelanin protects _Legionella_ from possible light-induced damage and helps it to obtain iron, an essential micronutrient for its survival [51; 58].