Bacterial Ultrastructure

BACTERIAL TOXINS

Although bacteria are associated with disease, only a few species are disease-producing or pathogenic for healthy individuals . Of greater concern are those organisms that, if presented with the correct set of conditions, can cause disease, i.e. opportunist pathogens. Examples include Staphylococcus epidermidis, a beneficial organism when present on the skin (its normal habitat) yet potentially fatal if attached to a synthetic heart valve, and Ps. aeruginosa, a non-pathogenic environmental organism but again potentially lethal in immunocompromised patients.

The pathogens cause host damage in a number of ways. In most cases pathogens produce a variety of molecules or factors that promote pathogenesis, among which are the toxins: products of bacteria that produce immediate host cell damage. Toxins have been classified as either endotoxin, i.e. cell wall-related, or exotoxin, products released extracellularly as the organism grows.

Endotoxin is the lipid A component of LPS. It possesses multiple biological properties including the ability to induce fever, initiate the complement and blood cascades, activate B lymphocytes and stimulate production of tumour necrosis factor. Endotoxin is generally released from lysed or damaged cells. Care must be taken to eliminate or exclude such heat-resistant material from parenteral products and their delivery systems through a process known as de-pyrogenation.

Most exotoxins fall into one of three categories on the basis of their structure and activities. These are the AB toxins, the cytolytic toxins and the superantigen toxins. The AB toxins consist of a B subunit that binds to a host cell receptor and is also covalently bound to the A subunit that mediates the enzymic activity responsible for toxicity. Most exotoxins (e.g. diphtheria toxin, cholera toxin) are of the AB category. The cytolytic toxins such as haemolysins and phospholipases do not have separable A and B portions but work by enzymatically attacking cell constituents, causing lysis. The superantigens also lack an AB type structure and act by stimulating large numbers of immune response cells to release cytokines, resulting in a massive inflammatory reaction. An example of this type of reaction is Staphylococcus aureus-mediated toxic shock syndrome.