genes. The expression of which is under the control of phrase variation (). This is opa due to slipped-strand mispairing of a five nucleotide length repeat sequence in the open reading frame of the protein (). Phase variation allows expression of Opa proteins to change at random. There is considerable diversity in the Opa sequence within the species; however there is a relative conservation of certain combinations of alleles within strains. This may be due to a fitness advantage of particular combinations in aiding adhesion of the bacterium to a range of human host receptors (). The affinity and tropism of different members of the CEACAM family may be influenced by sequence variation in the Opa protein, specifically in the variable loops (). CEACAM expression is upregulated due to inflammatory cytokines. This can lead to increased clustering of the protein in the cellular surface, resulting in an increase in the strength of the interaction between meningococcus and the host cell (). The Opc protein is a structurally unrelated adhesin which is also responsible for tight adhesion. It has a 10-stranded structure and is encoded by a single gene. The β-barrel target for Opc is HSPGs (). It is also capable of binding onto components of the extracellular matrix such as vitronectin and fibronectin (). These interactions may act as a bridge, allowing for both direct and indirect interaction with HSPGs (). 1.3.4.3. Polysaccharide Capsule Expression of the polysaccharide capsule of meningococcus is associated with a reduced ability to adhere to epithelial cells (), with acapsulated strains more commonly isolated from the nasopharynx. This may be due to its hydrophilic nature and steric hindrance of the polysaccharide which can impede interaction with the host membrane. Acapsulated bacteria can engage more tightly with the host epithelium through the use of Opa and Opc. However in invasive disease the capsule promotes bacterial survival by providing resistance to environmental factors and the host immune system (). Phase variation in capsule expression may occur over the course of a disease, allowing for optimum success during the separate adhesion and invasion events. Following into the bloodstream, the pathogen must avoid numerous components of the host’s innate immune response. This includes tissue-located macrophages,
opa genes. The expression of which is under the control of phrase variation (). This is due to slipped-strand mispairing of a five nucleotide length repeat sequence in the open reading frame of the protein (). Phase variation allows expression of Opa proteins to change at random. There is considerable diversity in the Opa sequence within the species; however there is a relative conservation of certain combinations of alleles within strains. This may be due to a fitness advantage of particular combinations in aiding adhesion of the bacterium to a range of human host receptors (). The affinity and tropism of different members of the CEACAM family may be influenced by sequence variation in the Opa protein, specifically in the variable loops (). CEACAM expression is upregulated due to inflammatory cytokines. This can lead to increased clustering of the protein in the cellular surface, resulting in an increase in the strength of the interaction between meningococcus and the host cell (). The Opc protein is a structurally unrelated adhesin which is also responsible for tight adhesion. It has a 10-stranded β-barrel structure and is encoded by a single gene. The target for Opc is HSPGs (). It is also capable of binding onto components of the extracellular matrix such as vitronectin and fibronectin (). These interactions may act as a bridge, allowing for both direct and indirect interaction with HSPGs (). 1.3.4.3. Polysaccharide Capsule Expression of the polysaccharide capsule of meningococcus is associated with a reduced ability to adhere to epithelial cells (), with acapsulated strains more commonly isolated from the nasopharynx. This may be due to its hydrophilic nature and steric hindrance of the polysaccharide which can impede interaction with the host membrane. Acapsulated bacteria can engage more tightly with the host epithelium through the use of Opa and Opc. However in invasive disease the capsule promotes bacterial survival by providing resistance to environmental factors and the host immune system (). Phase variation in capsule expression may occur over the course of a disease, allowing for optimum success during the separate adhesion and invasion events. Following into the bloodstream, the pathogen must avoid numerous components of the host’s innate immune response. This includes tissue-located macrophages,
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