**10. Conclusion**

92 The Complex World of Polysaccharides

gastric receptor.

development of gastric atrophy [70].

intrinsic resistance to these factors [71].

**9.2. Changes in the LPS related to resistance** 

mediated by the regulation of the expression of genes. By varying their antigenicity, the pathogens have a greater ability to evade the immune response of the host, and this

The O antigen is considered to be highly immunogenic and induces the production of antibodies that may activate the complement pathway, either through the classic pathway or an alternate pathway, which leads to cellular death or phagocytosis. Certain modifications in the oligosaccharide chain of the O antigen may alter the interaction of the complement pathway. Several O antigens of pathogens are similar to host molecules and facilitate invasion through mimicking in the host; for example, O antigens of the LPS of *H. influenzae* 

The mimicking property may also serve to evade the immune system, as is the case of *H. pylori.* The chains of the O antigen that contain the surface of the LPS of *H. pylori* express Lewis antigens, mainly Lex and Ley, although some isolates may contain other antigens, such

The expression of Lewis antigens and their fucosylation have biological effects in the pathogenesis of this bacterium. The O antigen of *H. pylori* exhibits molecular mimicking with the Lewis antigens of the host within the gastric epithelium. The expression of the Lewis antigens is subject to phase variation, given that the regulation of the glycosyltransferase genes is regulated by SSM, which in the O antigen structure promotes variations among the strains. The antigenic mimicking is essentially involved in the evasion of the immune system and gastric adaptation. Several studies show that mimicking also plays a role in the colonisation and adhesion of Lex of the bacteria with the galectin-3 of a

Moreover, *H. pylori* is capable of evading the binding effect of surfactant protein D, which is expressed in the gastric mucosa and is a component of the innate immune response [69]. This microorganism impedes the bonding of the surfactant protein through the variation of its LPS. This phenomenon is associated with changes in the fucosylation of the O antigen chain. In addition, the expression of Lewis antigens affects both the inflammatory response and the polarisation of the T cells that are triggered after an infection. Because it is a chronic pathogen, several studies have shown that *H. pylori* may induce anti-Lewis auto-reactive antibodies, which enable the gastric mucosa to be recognised and contribute to the

The hydrophobic antibiotics that reach the interior of the cells due to the permeability of the external membrane are aminoglycosides, macrolides, rifamycins, novobiocin, fusidic acid and cationic peptides. The tetracycline and the quinolones use pathways that are mediated by lipids and porins. The central region of the LPS is important because it provides a barrier against hydrophobic antibiotics and other components; isolates that express a long LPS have

as Lea, Leb, Lec, Sialyl-Lex and H-1, in addition to type A and B blood groups [68].

variability makes it more difficult to design vaccines for these pathogens [66].

and of *N. gonorrhoeae* mimic epitopes of glycosphingolipids [67].

In the bacterial pathogens, the most variable structures are those expressed in the cell surface. LPS is one of the principal antigenic structures of cell surface of gram-negative bacteria. A great variability in LPS has been demonstrated and principally in O antigen of gram-negative bacteria. This variability is present not only in the longitude of the oligosaccharide chains but also in the composition and structure of LPS.

Many of the functions of O antigen are associated to the longitude of the chain and to the variability of its structural features. This variability could affect the function, physical and chemical properties as well as the target site of LPS and determines the changes in the virulence of the microorganism that favor its adaptation to fluctuating enviroment which in many occasions are hostile to the microorganism and permit its evasion of the immune response of the host. The variation in O antigen structure has demonstrated that its composition and the longitude of its chain could be biological markers of virulence and this characteristic could differ within the same bacterial strain. The variability of LPS could derive from adaptations that involve associated changes to the synthesis of this molecule. The antigenic variability could occur by means of genetic and epigenetic mechanisms. The lost or gain of genes associated to variability of LPS is due to the events of genetic material interchange produced by lateral transference of genes which leads to strain selection with new characteristics and the evolution of the bacteria by modification of this structure.

One of the most important aspects of LPS function is its participation as immunogenic molecule and its role in bacterial classification based on O antigen and its variability. In general, it is seen that the modifications of O antigen play an important role in the process of infection including the adherence, the colonization, and the ability to evade defensive mechanisms of the host especially the innate resistance.

The study of the events of variation of LPS and its effects on pathogenecity and virulence represents a field of study of great interest to understand bacterial physiology and its mechanisms of adaptation and evolution.

The immunogenicity and variability of O antigen confer to gram-negative bacteria an important characteristic for its serological typification. The 0-antigen is subject to an intense selection on the part of immune system, which could be the principal factor for the different forms in which it is presented. For this reason, the variability of O antigen has been an area of intense research.
