Table 1-4. Components of milk proven to affect bacterial adhesion. Milk Constitute Bacterium Reference Fucosyloligosaccharides Escherichia coli () Free oligosaccharides Neisseria meningitidis () Polymeric glycans Pseudomonas aeruginosa and Chromobacterium violaceum () Lactoferrins Shigella spp. () Caseins Streptococcus mutans () 1.2.2.7. Probiotics as Anti-Adhesive Agents Probiotic approaches involve the use of bacterial species at the site of infection as a preventative to stop pathogens from reaching a critical density required to cause disease (Figure 1-3E). These beneficial bacteria are usually derived from the natural flora of the body, hence are indistinguishable from commensal bacteria and so do not activate an immune response. They can act to reduce the binding of detrimental microorganisms through a number of mechanisms; the exact mode of action has not been clearly defined. Evidence suggests there is some competition for colonisation space. In the intestinal tract, this has been shown to occur at cell surface receptors of enterocytes, probiotic bacterial strains can displace pathogenic bacteria (). They may also outcompete the pathogen for vital nutrients for growth. Alternatively probiotic agents may limit other bacterial binding by increasing the production of intestinal mucins, improving barrier function (). Finally commercialised probiotic Lactobacillus plantarum has been shown to secrete extracellular protein BMCM12 that can reduce adherence of E. coli and S. enterica subsp. enterica to mucin, possibly reducing enteropathogen binding to mucus layer of the intestine (). The most commonly used probiotic species are lactobacilli and bifidobacteria. is evidence of a negative correlation between colonisation with these probiotic species and rates of certain infections in animal models and clinical trials. In a clinical conducted on women with a history of recurrent bacterial vaginosis, a daily vaginal capsule containing Lactobacillus rhamnosus, Lactobacillus acidophilus and Streptococcus thermophilus administered on 14 days over a 3 week period reduced
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,