TRIPASS XR تري باس

 Virulence factors are those characteristics of a bacterium that enhance its pathogenicity, that is, properties

that enable a microorganism to establish itself and replicate on or within a specific host; they are as

follows:

8

Arranged by Sarah Mohssen

Section I– Microbiology Introductory By Dr. Mohammed Ayad

1. Entry into the host

The first step of the infectious process is the entry of the microorganism into the host by one of several

ports: by the respiratory, GI, or urogenital tract or through skin that has been cut, punctured, or burned.

Once entry is achieved, the pathogen must overcome diverse host defenses before it can establish itself.

These include phagocytosis; the acidic environments of the stomach and urogenital tract; and various

hydrolytic and proteolytic enzymes found in the saliva, stomach, and small intestine.

Bacteria that have an outer polysaccharide capsule (for example, Streptococcus pneumoniae and

Neisseria meningitidis) have a better chance of surviving these primary host defenses.

2. Adherence to host cells

Some bacteria (e.g. Escherichia coli) use pili to adhere to the surface of host cells. Group A Streptococci

have similar structures (fimbriae). Other bacteria have cell surface adhesion molecules or particularly

hydrophobic cell walls that allow them to adhere to the host cell membrane.

The adherence enhances virulence by preventing the bacteria from being carried away by mucus or

washed from organs with significant fluid flow, such as the urinary and the GI tracts. Adherence also

allows each attached bacterial cell to form a microcolony. An example of the importance of adhesion is

that of Neisseria gonorrhoeae in which strains that lack pili are not pathogenic.

3. Invasiveness

Invasive bacteria are those that can enter host cells or penetrate mucosal surfaces, spreading from the

initial site of infection. Invasiveness is facilitated by several bacterial enzymes, the most notable of which

are collagenase and hyaluronidase. These enzymes degrade components of the extracellular matrix,

providing the bacteria with easier access to host cell surfaces.

Many bacterial pathogens express membrane proteins known as "invasins" that interact with host cell

receptors, thereby eliciting signaling cascades that result in bacterial uptake by induced phagocytosis.

Invasion is followed by inflammation, which can be either pyogenic (involving pus formation) or

granulomatous (having nodular inflammatory lesions), depending on the organism.

The pus of pyogenic inflammations contains mostly neutrophils, whereas granulomatous lesions contain

fibroblasts, lymphocytes, and macrophages.

4. Iron sequestering

Iron is an essential nutrient for most bacteria. To obtain the iron required for growth, bacteria produce

iron-binding compounds, called siderophores. These compounds capture iron from the host by chelation,

and then the ferrated siderophores binds to specific receptors on the bacterial surface. Iron is actively

transported into the bacterium, where it is incorporated into essential compounds such as cytochromes.

The pathogenic Neisseria species are exceptions in that they do not produce siderophores but instead

utilize host iron-binding proteins, such as transferrin and lactoferrin, as iron sources.

Virulence factors that inhibit phagocytosis

1. The most important antiphagocytic structure is the capsule external to the cell wall, such as in S.

pneumoniae and N. meningitidis.

9

Arranged by Sarah Mohssen

Section I– Microbiology Introductory By Dr. Mohammed Ayad

2. The second group of antiphagocytic factors is the cell wall proteins of gram-positive cocci, such as

protein A of Staphylococcus and M protein of group A Streptococci.

5- Bacterial toxins

Some bacteria cause disease by producing toxic substances, of which there are two general types:

exotoxins and endotoxin. Exotoxins, which are proteins, are secreted by both gram-positive and gramnegative bacteria.

In contrast, endotoxin, which is lipopolysaccharide (LPS), is not secreted but instead is an integral

component of the cell walls of gram-negative bacteria.

a. Exotoxins: These include some of the most poisonous substances known. It is estimated that as little

as 1 μg of tetanus exotoxin can kill an adult human. Exotoxin proteins generally have two polypeptide

components. One is responsible for binding the protein to the host cell, and one is responsible for the toxic

effect.

In several cases, the precise target for the toxin has been identified. For example, diphtheria toxin is an

enzyme that blocks protein synthesis. It does so by attaching an adenosine diphosphate–ribosyl group to

human protein elongation factor EF-2, thereby inactivating it. Most exotoxins are rapidly inactivated by

moderate heating (60o C), notable exceptions being Staphylococcal enterotoxin and E. coli heat-stable

toxin (ST).

Also, treatment with dilute formaldehyde destroys the toxic activity of most exotoxins but does not affect

their antigenicity.

Formaldehyde-inactivated toxins, called toxoids, are useful in preparing vaccines.

Exotoxin proteins are, in many cases, encoded by genes carried on plasmids or temperate bacteriophages.

An example is the diphtheria exotoxin that is encoded by the tox gene of a temperate bacteriophage that

can lysogenize Corynebacterium diphtheriae. Strains of C. diphtheriae that carry this phage are

pathogenic, whereas those that lack the phage are nonpathogenic.

b. Endotoxins: These are heat-stable, LPS components of the outer membranes of gram-negative (but

not gram-positive) bacteria. They are released into the host’s circulation following bacterial cell lysis.

LPS consists of polysaccharide composed of repeating sugar subunits (O antigen), which protrudes from

the exterior cell surface; a core polysaccharide; and a lipid component called lipid A that is integrated into

the outer leaflet of the outer membrane.

The lipid A is responsible for the toxicity of this molecule. The main physiologic effects of LPS

endotoxin are fever, shock, hypotension, and thrombosis, collectively referred to as septic shock. These

effects are produced indirectly by macrophage activation, with the release of cytokines, activation of

complement, and activation of the coagulation cascade. Death can result from multiple organ failure.

Elimination of the causative bacteria with antibiotics can initially exacerbate the symptoms by causing

sudden massive release of endotoxin into the circulation. Although gram-positive bacteria do not contain

LPS, their cell wall peptidoglycan and teichoic acids can elicit a shock syndrome similar to that caused

by LPS but usually not as severe.