Resistance to Host Defences - Consolidation

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Chapter: Pharmaceutical Microbiology : Principles Of Microbial Pathogenicity And Epidemiology

Most bacterial infections confine themselves to the surface of epithelial tissue (e.g. Bordetella pertussis, Corynebacterium diphtheriae, Vibrio cholerae). This is, to a large extent, a reflection of their inability to combat that host’s deeper defences.


RESISTANCE TO HOST DEFENCES

 

Most bacterial infections confine themselves to the surface of epithelial tissue (e.g. Bordetella pertussis, Corynebacterium diphtheriae, Vibrio cholerae). This is, to a large extent, a reflection of their inability to combat that host’s deeper defences. Survival at these sites is largely due to firm attachment to the epithelial cells. Such organisms manifest disease through the production and release of toxins (see below).

 

Other groups of organisms regularly establish systemic infections after traversing the epithelial surfaces (e.g. Brucella abortus, Salmonella enterica serovar Typhi, Streptococcus pyogenes). This property is associated with their abilities either to gain entry into susceptible cells and thereby enjoy protection from the body’s defences, or to be phagocytosed by macrophages or polymorphs and yet resist their lethal action and multiply within them. Other organisms are able to multiply and grow freely in the body’s extracellular fluids. Microorganisms have evolved a number of different strategies that allow them to suppress the host’s normal defences and thereby survive in the tissues.

 

1) Modulation of the inflammatory response

 

Growth of microorganisms releases cellular products into their surrounding medium, many of which cause nonspecific inflammation associated with dilation of blood vessels. This increases capillary flow and access of phagocytes to the infected site. Increased lymphatic flow from the inflamed tissues carries the organisms to lymph nodes where further antimicrobial and immune forces come into play. Many of the substances that are released by microorganisms in this fashion are chemotactic towards polymorphs that tend, therefore, to become concentrated at the site of infection: this is in addition to the inflammation and white blood cell accumulation that is associated with antibody binding and complement fixation . Many organisms have adapted mechanisms that allow them to overcome these initial defences. Thus, virulent strains of Staph. aureus produce a mucopeptide (peptidoglycan), which suppresses early inflammatory oedema, and related factors that suppress the chemotaxis of polymorphs.

 

2) Avoidance of phagocytosis

 

Resistance to phagocytosis is sometimes associated with specific components of the cell wall and/or with the presence of capsules surrounding the cell wall. Classic examples of these are the Mproteins of the streptococci, the polysaccharide capsules of the pneumococci and the alginatelike slime associated with Ps. aeruginosa infections of the cysticfibrotic lung. The acidic polysaccharide Kantigens of Escherichia coli and S. enterica serovar Typhi behave similarly, in that (1) they can mediate attachment to the intestinal epithelial cells, and (2) they render phagocytosis more difficult. Generally, possession of an extracellular capsule and/or slime will reduce the likelihood of phagocytosis.

 

Microorganisms are more readily phagocytosed when coated with antibody (opsonized). This is due to the presence on the white blood cells of receptors for the Fc fragment of IgM and IgG. Avoidance of opsonization will clearly enhance the chances of survival of a particular pathogen. A substance called protein A is released from actively growing strains of Staph. aureus , which acts by nonspecific binding to IgG at the Fc region, at sites both close to, and remote from, the bacterial surface. This blocks the Fc region of bound antibody masking it from phagocytes. Protein A–IgG complexes remote from the infection site will also bind complement, thereby depleting it from the plasma and negating its actions near to the infection site. 

 

3) Survival following phagocytosis

 

Death of microorganisms following phagocytosis can be avoided if the microorganisms are not exposed to the killing and digestion processes within the phagocyte. This is possible if fusion of the lysosomes with phagocytic vacuoles can be prevented. Such a strategy is employed by virulent Mycobacterium tuberculosis, although the precise mechanism is unknown. Other bacteria seem able to grow within the vacuoles despite lysosomal fusion (Listeria monocytogenes, S. enterica serovar Typhi). This can be attributed to cell wall components that prevent access of the lysosomal substances to the bacterial membranes (e.g. Brucella abortus, mycobacteria) or to the production of extracellular catalase which neutralizes the hydrogen peroxide liberated in the vacuole (e.g. staphylococci).

 

If microorganisms are able to survive and grow within phagocytes, they will escape many of the other body defences such as the lymph nodes, and be distributed around the body. As the lifespan of phagocytes is relatively short, such bacteria will eventually be delivered to the liver and gastrointestinal tract where they are ‘recycled’.

 

4) Killing of phagocytes

 

An alternative strategy is for the microorganism to kill the phagocyte. This can be achieved by the production of leucocidins (e.g. staphylococci, streptococci) which promote the discharge of lysosomal substances into the cytoplasm of the phagocyte rather than into the vacuole, thus directing the phagocyte’s lethal activity towards itself.

 

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