However, the microorganisms’s capsule, and, in the

However, some bacteria are known to have special structures that protect them from the host’s defenses, whereas others may secrete substances that contribute to their virulence. Some of the factors believed to contribute to pathogenicity are described below.

Capsules:

Some pathogenic bacteria possess large capsules surrounding their cell walls. The ability of one of these organisms to produce disease depends upon the presence of this capsule, and loss of the capsule (as a result of mutation) invariably results in a concomitant loss of the ability to produce disease.

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The possession of a capsule contributes to an organism’s disease-producing potential by preventing phagococytosis- engulfment of the encapsulated organisms by the host’s phagocytic cells.

The exact reason for this antiphagocytic activity is not known, but it seems to be due to surface properties of the capsule that prevent the phagocyte from forming a sufficiently intimate contact with the microorganisms to allow phagocytosis to take place.

As we shall see later, the presence of specific antibodies to the capsular material provides receptors for the phagocyte and permits phagocytosis to occur.

For example, immunity to infection by Streptococcus pneumoniae depends upon antibody to the microorganisms’s capsule, and, in the presence of this antibody, the invading organism is rapidly engulfed and destroyed by the host’s leukocytes, that is, the antibody is functioning as an opsonin.

Pili or Fimbriae:

We shall use the terms pili and fimbriae synonymously and immediately point out that many non-disease-producing bacteria possess pili, just as many nonpathogenic bacteria possess capsules.

This obviously demonstrates that neither capsules nor pili are the sole determinants for the virulence of microorganisms. However, it is known that the possession of pili endows a bacterium with an enhanced ability to adhere to other bacteria and to the membranes of the host’s cells and phagocytes.

Thus, in at least several instances (such as Neisseria gonorrhoeae, the cause of gonorrhea, and enterotoxigenic Escherichia coli, and a cause of gastroenteritis) the possession of pili appears to be associated with virulent strains.

Exotoxins:

Many pathogenic organisms do not possess antiphagocytic structures such as capsules or pili but have other characteristics that permit them to evade normal host defenses. For many microbes, these include the production and secretion of toxic substances.

Some of these products, called exotoxins, are responsible for the symptoms of such diseases as diphtheria, tetanus, gas gangrene, scarlet fever, the staphylococcal scalded-skin syndrome, and toxic shock syndrome.

In addition, certain types of food poisoning, such as those caused by Clostridium botulinum, Clostridium perfringens, and Staphylococcus aureus, are also due to the presence of exotoxic substances.

There are other pathogenic organisms that neither possess anti­phagocytic capsules nor produce exotoxins. With these, it is somewhat more difficult to pinpoint the properties responsible for virulence.

However, an array of substances (some of which are enzymes) secreted by some bacteria may play an important role in their ability to cause disease. Many of these substances have not been isolated, purified, or chemically characterized, and they have been given names based on observations of the biological or chemical activities of crude materials.

A few of the more commonly found extracellular products include various hemolysins, which lyse red blood cell leukocidins, which kill leukocytes; hyaluronidase, which hydrolyzes the hyaluronic acid of connective tissue; collagenase, which hydrolyzes collagen; coagulase, which coagulates plasma to form fibrin clots; and streptokinase an enzyme that indirectly lyses plasma clots.

Still another type of excreted virulence factor is exemplified by siderophores; these are phenolates or hydroxamates that, in some cases, can successfully obtain microbial growth-essential iron from the tranferrin or kctoferrin of the host.

Endotoxins:

Endotoxins are large molecules of lipopolysaccharide that are normal components of the cell walls of all gram-negative organisms. They are not excreted by the cell but are liberated during the lysis of gram-negative cells; they are also able to manifest their toxicity while still attached to the bacterial wall.

The biological effects of endotoxins are manifold but the two particularly prominent effects of an infection with gram-negative organisms are fever and shock.

Humans are particularly sensitive to minute amounts of endotoxins, and often a mild gram-negative bacterial infection will cause fever. Larger amounts of endotoxins may cause irreversible shock; this is seen in association with a fulminating gram-negative bacteremia.

Despite the toxicity of endotoxins a microbe’s pathogenicity is not entirely explained by its content of endotoxins. Undoubtedly, many of the symptoms of infections by organisms such as Salmonella typhi or Neisseria meningitides are a result of endotoxins, but the fact that many non pathogenic gram-negative bacteria possess equally toxic endotoxins and do not normally produce disease indicates that endotoxin by itself is not the major determinant of virulence by these organisms.

It is now evident that a number of different factors must come into play for a disease agent to produce an infection. At the outset, the portal of entrance must be suitable for the particular pathogen.

In many cases, a microorganism is restricted to only one portal of entry— for example, the typhoid fever organism (S. typhi) must be swallowed and must reach the small intestine in large numbers to cause disease.

On the other hand, S. aureus can use multiple portals of entry; it can cause pneumonia by way of the respiratory route, boils and furuncles by way of the skin, internal abscesses by way of the blood, or food poisoning by way of the gastrointestinal tract.

The ability to exit from the body and survive in the outside world is also an important factor in disease development. Some organisms, such as N. meningitidis and N. gonorrhoeae, are extremely sensitive to drying and will die after several hours outside the host.

Organisms such as the tubercle bacillus, however, may survive in dried sputum or secretions for months and still maintain their pathogenicity.