Virulence Factors for Viruses and Prokaryotes

organisms enter through endocytosis, while others simply enter the cell by producing an invasive protein that binds to the host cell.

Infection involves multiplication of the organism. Local infections involve a small body area, usually near the portal of entry. Some infections are focal but can spread to a secondary infection elsewhere in the body. Systemic infections involve a widely disseminated organism. Primary infections involve just one pathogen, while a secondary infection involves another pathogen. An example is a bacterial pneumonia after getting influenza.

The disease needs to be transmitted in order to pass the disease onto a secondary host. This usually means there must be a portal of exit, which can be the same as the portal of entry or not. It can involve sneezing, direct contact, semen, feces, sweat, or tears—each of which can be a good vehicle to pass on the infection. Vectors can also be part of the transmissibility of the organism.

VIRULENCE FACTORS FOR VIRUSES AND PROKARYOTES

There are specific virulence factors that confer a certain level of virulence of a pathogen. These are generally genetic in origin. The absence of certain genes that later diminish virulence is in keeping with the molecular Koch’s postulates.

An adhesin is either a protein or glycoprotein that will attach to receptors on a host cell. Bacteria, fungi, viruses, and protozoans will all have adhesins. E. coli that is enterotoxigenic has fimbriae that contain an adhesin which binds to the host cell. Many other bacteria have proteinaceous or glycoprotein-containing adhesins.

Invasion of the bacteria often involves toxins or enzymes. The invasion process often involves the bloodstream and elements of the immune system. The presence of organisms can involve bacteremia or bacteria in the blood, viremia or viruses in the blood, toxemia or toxins in the blood, or septicemia, which is the multiplication of the bacteria in the bloodstream. Septic shock refers specifically to hypotension and organ failure that can happen with a patient who has septicemia. Toxins can cause septic shock as well.

Exoenzymes are enzymes in an organism that assists in the organism’s invasion process. Some will help the organism fight the immune system. An example is hyaluronidase, which is an enzyme from bacteria that degrades the cement between adjacent cellular structures in the connective tissue. There are nucleases that degrade DNA, phospholipases that degrade cell walls, and proteases that degrade proteins. One protease is called collagenase, which is a major part of connective tissue. It is seen in gas gangrene caused by Clostridium perfringens.

Toxins are important to invasion and tissue damage. Certain pathogens will release toxins. There are endotoxins and exotoxins. Endotoxins are found on the bacterium itself. These can be released when the cell divides or dies off. Lipid A on gram-negative bacteria is an endotoxin. It triggers an immune response in the host. Too much of an immune response can lead to sepsis and host death.

Exotoxins are mostly made by gram-positive bacteria. These are different from endotoxins, which have specific actions on the host cells rather than just triggering an immune response. Exotoxins are heat labile so they can be inactivated but they are far more lethal than endotoxins. Exotoxins are proteins, while endotoxin is a part of a lipopolysaccharide.

There are three types of exotoxins. There are those that target something within the cell, called intracellular targeting toxins. There are membrane disrupting toxins, which damage the host cell membrane, and there are superantigen toxins, which activate the immune system.

Examples of intracellular targeting toxins are those leading to cholera, tetanus, botulism, and diphtheria. Membrane-disrupting toxins include those from Pseudomonas, Clostridium perfringens, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. Superantigens are those that cause staphylococcal toxic shock syndrome and certain streptococcal infections from Streptococcus pyogenes.

There are two parts to an intracellular targeting toxin, an A subunit and a B subunit. The B subunit is the one that gives the toxin its host cell specificity, while the A subunit confers the actual toxic response. The toxin is brought into the cell through endocytosis.

Diphtheria exotoxin is an AB toxin that inhibits protein synthesis. Cholera enterotoxin has an A subunit that increases cyclic AMP, leading to excessive fluid and electrolyte secretion into the gut. Botulinum toxin is a neurotoxin that is the most toxic substance in the world. The A subunit is a protease that blocks the release of the neurotransmitter that helps skeletal muscle contract. The tetanus toxin blocks the release of GABA, another neurotransmitter, in the tissues, leading to permanent muscle contractions.

Membrane disrupting toxins may form pores in the cell membrane or may disrupt the lipid bilayer of the cell. Hemolysins and leukocidins cause pores to form in the cell membrane. Streptolysin is made by Streptococcus pyogenes; it causes a pore to form in erythrocytes or red blood cells. Staphylococcus aureus and Streptococcus pneumoniae both produce these types of toxins.

Toxins that degrade the cell membrane include phospholipases, made by Rickettsia, Legionella, and Bacillus anthracis. These can lyse the phagosomes inside phagocytes. Clostridium perfringens, Pseudomonas aeruginosa, and certain beta-Staphylococcus aureus species make phospholipases that degrade the cell wall.

Superantigens trigger a massive immune response. They cause cells to secrete cytokines, which are chemical messengers in the immune system. There will be hypotension, high fever, and multiple organ failure from toxic shock. Toxic shock syndrome is an example of this but it can also happen with Streptococcus pyogenes.

There are virulence factors in prokaryotes that help the organism evade the immune system. Bacterial capsules can help prevent ingestion of the organism by the phagocytes. Streptococcus pneumoniae can do this. Those that are encapsulated tend to be more virulent than those without capsules. Other organisms will produce proteases to prevent phagocytosis. They can attack and destroy antibodies that aid in the phagocytic process. Fimbriae will contain proteins that block complement from binding so that phagocytosis doesn’t occur. Mycobacterium tuberculosis will make a mycolic acid substance that resists killing by the phagolysosome of the phagocyte.

Other bacteria make coagulase, which causes blood clotting and the coating of the bacterium with fibrin, which prevents phagocytosis. This is true of Staphylococcus aureus. There are also kinases that digest fibrin clots so that pathogens can escape a