VIRULENCE FACTORS

Are phenotypic characteristics that enable microbes to be virulent or to cause a disease,

and one of the obvious virulence factor are Toxins.

Attachment
When a certain pathogen gained access to the body, they can be able to attach or cause
disease to a host cell.

Receptors and Adhesins

A pathogens that are able to recognize and attach to
A particular pathogen can only attach to cells bearing the appropriate receptor
(glycoprotein).

*Certain viruses cause respiratory infections because they are able to recognize and
attach to certain receptors that are present on cells that line the respiratory tract. Because
those particular receptors are not present on cells lining the gastrointestinal tract, the virus
is unable to cause gastrointestinal infections. Similarly, certain viruses cause infections
in dogs, but not in humans, because dog cells possess a receptor that human cells lack.

*S. pyogenes is a cell that has an adhesin (called protein F). On their surfaces that enables
this pathogen to adhere to a protein—fibronectin—that is found on many host cell
surfaces. Human immunodeficiency virus (HIV; the virus that causes acquired
immunodeficiency syndrome [AIDS]) is able to attach to cells bearing a surface receptor
called CD4. Such cells are known as CD4_ cells. A category of lymphocytes called T-
helper cells (the primary target cells for HIV) are examples of CD4_ cells.

Adhesin and ligand a molecules on a pathogen’s surface that recognize and attach to
receptors on a host cell’s surface.

*For example, the adhesin on the envelope of HIV that recognizes and binds to the CD4
receptor is a glycoprotein molecule designated gp120. (Entry of HIV into a host cell is a
rather complex event, requiring several adhesins and several co-receptors.)
Adhesin enable pathogens to attach to host cells, they are considered virulence factors.

*In some cases, antibodies directed against such adhesins prevent the pathogen from
attaching and, thus, prevent infection by that pathogen.
Bacterial Fimbriae (Pili) are long, thin, hairlike, flexible projections composed
primarily of an array of proteins called pilin. Fimbriae are considered to be virulence
factors because they enable bacteria to attach to surfaces, including various tissues within
the human body

*Fimbriated (piliated) strains of N. gonorrhoeae are able to anchor themselves to the

inner walls of the urethra and cause urethritis. (Virulent)

*Nonfimbriated (nonpiliated) strains of N. gonorrhoeae gain access to the urethra;

they are flushed out by urination and are thus unable to cause urethritis. (avirulent)

*Fimbriated strains of Escherichia coli that gain access to the urinary bladder are able
to anchor themselves to the inner walls of the bladder and cause cystitis. (Virulent)

*Nonfimbriated strains of E. coli gain access to the urinary bladder; they are flushed
out by urination and are unable to cause cystitis. ( avirulent)

M-protein serves as a virulence factor in two ways:

(a) It enables the bacteria to adhere to pharyngeal cells; and
(b) It protects the cells from being phagocytized by white blood cells (i.e., the M-protein
serves an antiphagocytic function).

* Other bacterial pathogens possessing fimbriae are Vibrio cholerae, Salmonella spp.,
Shigella spp., Pseudomonas aeruginosa, and Neisseria meningitidis. Because bacterial
fimbriae enable bacteria to colonize surfaces, they are sometimes referred to as
colonization factors.

Obligate Intracellular Pathogens

A certain pathogen like Gram-negative bacteria (Rickettsia and Chlamydia) that live
within host cells to survive and multiply.

* Rickettsias invade and live within endothelial cells and vascular smooth muscle cells;
capable of synthesizing proteins, nucleic acids, and adenosine triphosphate (ATP), but are
thought to require an intracellular environment because they possess an unusual
membrane transport system; they are said to have leaky membranes.

*chlamydias invade different types of cells, including conjunctival epithelial cells and
cells of the respiratory and genital tracts; produce ATP molecules, they preferentially use
ATP molecules produced by host cells; this has earned them the title of “energy
parasites.”

*Ehrlichia and Anaplasma spp. are intraleukocytic pathogens, whereas Plasmodium

and Babesia spp. are intraerythrocytic pathogens.
Facultative Intracellular Pathogens
Pathogens that can live both within and outside of host cells
*Ex. M. Tuberculosis

Intracellular Survival Mechanisms

Two most important categories of phagocytes in the human body (referred to as
“professional phagocytes”) are macrophages and neutrophils.

* Once phagocytized, most pathogens are destroyed within the phagocytes by hydrolytic
enzymes (e.g., lysozyme, proteases, lipases, DNase, RNase, myeloperoxidase), hydrogen
peroxide, superoxide anions, and other mechanisms. However, certain pathogens are
able to survive and multiply within phagocytes after being ingested.

* Mycobacterial cell walls contain waxes, and it is thought that these waxes protect the
organisms from digestion.

Capsules
Bacterial capsules serve as an antiphagocytic function (i.e., they protect encapsulated
bacteria from being phagocytized by phagocytic white blood cells).

* Phagocytes are unable to attach to encapsulated bacteria because they lack surface
receptors for the polysaccharide material of which the capsule is made. If they cannot
adhere to the bacteria, they cannot ingest them. Because encapsulated bacteria that gain
accesses to the bloodstream or tissues are protected from phagocytosis, they are able to
multiply, invade, and cause disease.

* Nonencapsulated bacteria, on the other hand, are phagocytized and killed.

Encapsulated bacteria include S. pneumoniae, Klebsiella pneumoniae, H. influenzae, and
N. meningitidis. The capsule of the yeast, Cryptococcus neoformans, is also considered
to be a virulence factor.

Flagella
are considered to be virulence factors because they enable flagellated (motile) bacteria to
invade areas of the body that nonflagellated (nonmotile) bacteria cannot reach.
* Difficult for phagocytes to catch a moving target.

Exoenzymes
Enable to evade host defense mechanisms, invade, or cause damage to body tissues.
(Include necrotizing enzymes, coagulase, kinases, hyaluronidase, collagenase,
hemolysins, and lecithinase.)
*The major mechanisms by which pathogens cause disease are certain exoenzymes
or toxins that they produce
Necrotizing Enzymes
Are exoenzymes that cause destruction of cells and tissues.

* Examples are the flesh-eating strains of S. pyogenes, which produce proteases and other
enzymes that cause very rapid destruction of soft tissue, leading to a disease called
necrotizing fasciitis
***Shy, yung picture nasa p.246, fig. 14-8*** labyu! :D
Coagulase
Is a virulence factor that causes clotting (S. aureus). Binds to prothrombin, forming a
complex called staphylothrombin.\
-Enable S. aureus to clot plasma and thereby to form a sticky coat of fibrin around
themselves for protection from phagocytes, antibodies, and other host defense
mechanisms.

Kinases
are exoenzymes that dissolve clots; therefore, pathogens that produce kinases are able to
escape from clots.

*Streptokinase is the name of a kinase produced by streptococci; has been used to treat
patients with coronary thrombosis. Because S. aureus produces both coagulase and
staphylokinase

*staphylokinase is the name of a kinase produced by staphylococci.

*S. aureus , not only can cause the formation of clots, but it can also dissolve them.

Hyaluronidase
“Spreading factor”
Enables pathogens to spread through connective tissue by breaking down hyaluronic
acid, the polysaccharide “cement” that holds tissue cells together.
*secreted by several pathogenic species of Staphylococcus, Streptococcus, and
Clostridium.

Collagenase
Breaks down collagen (the supportive protein found in tendons, cartilage, and bones);
enables the pathogens to invade tissues.

*Clostridium perfringens, amajor cause of gas gangrene, spreads deeply within the body
by secreting both collagenase and hyaluronidase.
Hemolysins
are enzymes that cause damage to the host’s red blood cells (erythrocytes).

* The hemolysins produced by a-hemolytic bacteria cause a partial breakdown of

hemoglobin in the red blood cells, resulting in a green zone around the colonies of a-
hemolytic bacteria. The hemolysins produced by B-hemolytic bacteria cause complete
lysis of the red blood cells, resulting in a clear zone around the colonies of B-hemolytic
bacteria

Lecithinase
is an exoenzyme that causes destruction of host cell membranes

*C. perfringens, the major cause of gas gangrene, is able to rapidly destroy extensive
areas of tissue, especially muscle tissue.

Toxins
The ability of pathogens to damage host tissues and cause disease may depend on the
production and release of various types of poisonous substances

*The two major categories of toxins are endotoxins and exotoxins

Endotoxins which are integral parts of the cell walls of Gram-negative bacteria, can
cause a number of adverse physiologic effects.

**Septicemia (often referred to as sepsis) is a very serious disease consisting of chills,

fever, prostration (extreme exhaustion), and the presence of bacteria or their toxins in the
bloodstream

** Substances that cause fever are known as pyrogens.

** Shock is a life-threatening condition resulting from very low blood pressure and an
inadequate blood supply to body tissues and organs, especially the kidneys and brain.

** The type of shock that results from Gram-negative sepsis is known as septic shock.

Exotoxins, on the other hand, are toxins that are produced within cells and then released
from the cells; are poisonous proteins that are secreted by a variety of pathogens; they are
often named for the target organs that they affect.

** Examples, include neurotoxins, enterotoxins, cytotoxins, exfoliative toxin,

erythrogenic toxin, and diphtheria toxin.
Neurotoxins -the most potent exotoxins, which affect the central nervous system.

**The neurotoxins produced by Clostridium tetani and Clostridium botulinum—

tetanospasmin and botulinal toxin— cause tetanus and botulism, respectively.
Tetanospasmin affects control of nerve transmission, leading to a spastic, rigid type of
paralysis in which the patient’s muscles are contracted
***Shy, p.248, fig. 14-9 :D
** Botulinal toxin also blocks nerve impulses but by a different mechanism, leading to a
generalized, flaccid type of paralysis in which the patient’s muscles are relaxed. Both
diseases are often fatal.

Enterotoxins - are toxins that affect the gastrointestinal tract, often causing diarrhea and
sometimes vomiting.

** Examples of bacterial pathogens that produce enterotoxins are Bacillus cereus, certain
serotypes of E. coli, Clostridium difficile, C. perfringens, Salmonella spp., Shigella spp.,
V. cholerae, and some strains of S. aureus.

Exfoliative toxin - (or epidermolytic toxin) of S. aureus causes the epidermal layers of
skin to slough away, leading to a disease known as scalded skin syndrome. S. aureus also
produces a variety of toxins that destroy cell membranes.

Erythrogenic toxin, produced by some strains of S. pyogenes, causes scarlet fever.

**Leukocidins are toxins that destroy white blood cells (leukocytes).

Diphtheria toxin, produced by toxigenic strains of C. diphtheriae, inhibits protein

synthesis. It kills mucosal epithelial cells and phagocytes and adversely affects the heart
and nervous system.

Mechanisms by which Pathogens Escape Immune Responses

Immunology, the study of the immune system. A primary role of the immune system is to
recognize and destroy pathogens that invade our bodies.
*** is discussed in detail in Chapter 16

Antigenic Variation
Some pathogens are able to periodically change their surface antigens, a phenomenon
known as antigenic variation.
***discusses detail in Chapter 16
Camouflage and Molecular Mimicry
Adult schistosomes (trematodes that cause schistosomiasis) are able to conceal their
foreign nature by coating themselves with host proteins—a sort of camouflage.

In molecular mimicry, pathogens cover their surface antigens with host proteins, so the
pathogens will not be recognized as being foreign.

Destruction of Antibodies
Several bacterial pathogens, including H. influenzae, N. gonorrhoeae, and streptococci,
produce an enzyme (IgA protease) that destroys IgA antibodies

** These pathogens are capable of destroying some of the antibodies that the host’s
immune system has produced in an attempt to destroy them.