**8. The regulation of virulence in the Staphylococci**

Virulence factors are the substances that aid in the pathogenesis of an organism. Pathogenesis of *Staphylococcus aureus* does not depend on a single factor and there are a set of substances that collectively leads to the successful colonization of that bacteria into its host [98–99]. These virulence factors also diversify in their composition of proteins as exoproteins and surface proteins. To date, there are many reports of mutants, which behave differentially concerning the expression of different exoproteins in different environmental conditions [100–102]. Most of the exoproteins are secreted at the post exponential phase. The polysaccharide of the capsule of *Staphylococcus aureus* also acts as the virulent factor. This bacterium can also be classified based on the structure of the capsule into 11 different serotypes [99]. Serotypes 1 and 2 and mucoid, while the serotypes 3 to 11 are microcapsules as which are non-mucoid and have thin capsules [96–101]. Among these 11 serotypes, 5 and 8 are the most prevalent. The capsule is vital to this bacterium as it is responsible for evading the phagocytosis by masking the C3b that is placed on the surface of these bacteria by the host immune cells. The significance of microcapsules in pathogenesis is not well established as there are many controversial studies in this regard. The genes responsible for the formation of microcapsules are cap5H, cap8J, and cap5P. The cap8B and cap5B genes are homologous to each other in several proteins, and cap8B acts as the chain length regulator of the capsule [98–100]. The chemical composition of serotypes 1, 2, 5, and 8 are presented in **Figure 4**.

The agr and sar 16 loci have been extensively studied and believed to have vital importance in the virulence of this bacteria. Alpha toxin is also a virulence factor of Staphyloccocus aureus, which forms the pores to the cells resulting in cytolysis of the surrounding cells of invasion [97–100]. Not all the virulence factors are active throughout the life of the bacteria, but on the as-required basis, to overcome the metabolic burden [96–100]. Currently, the exact mechanism behind these virulence factors is not well elucidated. Staphylococcus is blessed with these virulence factors for its survival in diversified environmental conditions, and the primary purpose of these is not to cause the disease. Passaging the bacteria to nutritive media in vitro leads to the bacteria of less virulency and the passage of bacteria to the live animal or host leads to the bacteria with more virulency [99, 100].

Microbial surface components recognizing adhesive matrix molecules (MSCRAMMS), Sialoprotein, laminin, elastin, etc. are the proteins that are responsible for the adhesion of staphylococcus to its surrounding [98–100].

**Figure 4.**

*The chemical compositions of serotypes 1, 2, 5, and 8. Modified from [99].*

Staphylococcus aureus *and the Veterinary Medicine DOI: http://dx.doi.org/10.5772/intechopen.100202*

To dodge the host immune system is a requirement of the successful colonization of each pathogen. Staphylococcus is also blessed with these factors as protein A for binding the IgG antibodies [99–101].

This bacterium has a system of coordination with environmental conditions as temperature, pH, etc. This system of coordination is named the "two-component systems" having two proteins and a single operon and upon detection of the signal these proteins active certain genes for transcription. A small colony-sized SVC subpopulation is also a potent strategy of this bacteria against the immune system of the host and antibiotic therapy [97, 98].

The bacterial secretions having mitogen properties are also called superantigens. These superantigens are pathogenic and may cause an autoimmune response. They are also responsible to activate macrophages, zinc having a vital role in that, by initiating the IFN-gamma secretion from T cells. Superantigens can initiate an immune response without the increased concentration of IFN-gamma, whereas in mice it is necessary to have the increased concentration of IFN-gamma to initiate the immune response. It is not clear whether the response of MHC I and MHC II are synergistic or not, in the immunologic response against the pathogenesis of Staphylococcus **Figures 5** and **6** [97–101].

**Figure 5.**

*(A) Response of IL-6 against anti-MHC-I 50* μ*g and MHC-II 100* μ*g antibodies incubated with C2D macrophages. (B) Response of TNF against anti-MHC-I 50* μ*g and MHC-II 100* μ*g antibodies incubated with C2D macrophages. Modified from [99–102].*

#### **Figure 6.**

*Response of TNF against various stimuli. (TNF: Tumor Necrosis Factor, SEA: Staphylococcal enterotoxin A, SEA-B: Staphylococcal enterotoxin A). Modified from [99].*
