Pathogenicity

   PATHOGENICITY - the ability of a microorganism to cause disease in a host; 
   an inherited property. Often the genes for this property reside in the extrachromosomal 
   plasmids. Disease symptoms are often the result of toxic or allergic reactions.

   VIRULENCE - the degree of pathogenicity of a microbe or a measure of the 
   ability of the microbe to cause disease. Virulence is determined by the 
   factors of INVASIVENESS and TOXIGENICITY.

   To cause disease, pathogens must penetrate the host tissues and multiply.
   Usually they become localized and form a small focus of infection. In 
   some cases, pus is formed and these are called PYOGENIC infections. 
   Within the body, localization usually occurs within the lymph nodes, 
   liver, spleen or kidney. From these foci of infection microbes may pass 
   into the bloodstream and set up the conditions of BACTEREMIA 
   (non-multiplying bacteria in the bloodstream) and SEPTICEMIA 
   (reproducing bacteria). 

Virulence Factors

	 The ability of microorganisms to invade and cause disease 	
         depends upon a number of factors.
   
   1. number of organisms - number required to produce disease
	 symptoms in a host is known as the INFECTIVE DOSE; the more
	 virulent the microbe the fewer the number needed
   2. the species of the microorganism involved - some are more
	 adept at surviving within the body; some multiply rapidly
   3. the number of species involved - in some cases, symptoms
	 only develop as the result of symbiotic reactions between 
	 several species; e.g. Vincent's Angina occurs only when
	 both Fusobacterium and Borrelia are present
   4. toughness of the host - the innate resistance of the host 	        
         due to non-specific bodily defenses often determines 	
         success or failure of the invading parasite
   5. ability to produce toxins - organisms which produce toxins
	 have a greater chance of breaching the body's defenses and
	 spreading

Types of Toxins

   1. EXOTOXINS - metabolic waste products of living bacteria;
	 usually protein (thus highly antigenic); destroyed by heat
	 and acids (60°C for 30 minutes); 
         most dangerous but most easily recognized and neutralized by
         antibodies (ANTITOXIN)

   2. ENDOTOXINS - given off by dead bacteria; most often Gram -;
	 more heat resistant; generally less toxic; consist of a 	
         mixture of phospholipids, carbohydrates, and proteins, thus 	 
         only slightly antigenic; often cause inflammatory reactions

Examples of Highly Virulent Pathogens

   Corynebacterium diphtheriae - weakly 
     invasive but highly toxigenic; organism remains localized in throat 
     while toxins are spread throughout the body

   Klebsiella pneumoniae - highly invasive but weakly 
      toxigenic; large numbers of organisms, each contributing a small 
      amount of endotoxin, create the problem

   Pathogens have a variety of mechanisms which allow them to avoid or 
   resist the host's defenses. Among these are:

CAPSULE or SLIME LAYER - prevents phagocytosis by white blood cells or at 
   least makes such action difficult; Group A streptococci contain M
   PROTEIN in their cell wall which also prevents phagocytosis 
   (see Scientific American, 9/91)

LEUKOCIDINS - enzymes produced by groups such as staphylococci and 
   streptococci which destroy (lyse) phagocytic white blood cells and 
   macrophages

PYROGENS - cause elevated temperatures in certain areas (fever)

HYALURONIDASE - often called the SPREADING FACTOR; this enzyme destroys 
   hyaluronic acid which is the intercellular cement which binds cells 
   together into tissues; this allows microbes to spread through a tissue 
   by moving between the cells; produced by strep-tococci and some 
   clostridia

COLLAGENASE - this enzyme, produced by some clostridia, breaks down 
   collagen, a protein found in muscle and connective tissue

STREPTOKINASE - an enzyme produced by streptococci which dissolves fibrin
   and thus breaks down clots; this causes a wound to leak and 
   streptococcal infections are often characterized as "weeping" wounds;
   has been used to dissolve clots formed in coronary arteries of heart
   attack victims

COAGULASE - an enzyme produced by some species of staphylococci which 
   coagulates (clots) fibrinogen; this may cause a walling off of the 
   microbe and protects it from phagocytosis

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