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Tag words: pathogenic bacteria, bacterial pathogenicity, invasiveness, toxigenesis, colonization, specific adherence, adhesin, receptor, invasion, invasin, coagulase, leucocidin, hemolysin, streptokinase, phagocytosis, phagosome, lysosome, phagolysosome, immunological tolerance, antigenic disguise, immunosuppression, antigenic variation, protein toxins, botulinum toxin, diphtheria toxin, anthrax toxin, tetanus toxin, pertussis toxin, cholera enterotoxin, adenylate cyclase, staph enterotoxin, TSST, pyrogenic exotoxin, superantigen, shiga toxin, E. coli LT toxin, ST toxin, endotoxin, lipopolysaccharide, LPS, Lipid A, O antigen, O polysaccharide, toxoid, pathogenicity island.









Kenneth Todar currently teaches Microbiology 100 at the University of Wisconsin-Madison.  His main teaching interest include general microbiology, bacterial diversity, microbial ecology and pathogenic bacteriology.

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Mechanisms of Bacterial Pathogenicity (page 2)

(This chapter has 8 pages)

© Kenneth Todar, PhD

COLONIZATION

The first stage of microbial infection is colonization: the establishment of the pathogen at the appropriate portal of entry. Pathogens usually colonize host tissues that are in contact with the external environment. Sites of entry in human hosts include the urogenital tract, the digestive tract, the respiratory tract and the conjunctiva. Organisms that infect these regions have usually developed tissue adherence mechanisms and some ability to overcome or withstand the constant pressure of the host defenses at the surface.

Bacterial Adherence to Mucosal Surfaces. In its simplest form, bacterial adherence or attachment to a eucaryotic cell or tissue surface requires the participation of two factors: a receptor and an ligand. The receptors so far defined are usually specific carbohydrate or peptide residues on the eucaryotic cell surface. The bacterial ligand, called an adhesin, is typically a macromolecular component of the bacterial cell surface which interacts with the host cell receptor. Adhesins and receptors usually interact in a complementary and specific fashion. Table 1 is a list of terms that are used in medical microbiology to refer to microbial adherence to surfaces or tissues.
 
TABLE 1. TERMS USED TO DESCRIBE ADHERENCE FACTORS IN HOST-PARASITE INTERACTIONS
ADHERENCE FACTOR DESCRIPTION
Adhesin A surface structure or macromolecule that binds a bacterium to a specific surface
Receptor A complementary macromolecular binding site on a (eucaryotic) surface that binds specific adhesins or ligands
Lectin Any protein that binds to a carbohydrate
Ligand A surface molecule that exhibits specific binding to a receptor molecule on another surface
Mucous The mucopolysaccharide layer of glucosaminoglycans covering animal cell mucosal surfaces
Fimbriae Filamentous proteins on the surface of bacterial cells that may behave as adhesins for specific adherence
Common pili Same as fimbriae
Sex pilus A specialized pilus that binds mating procaryotes together for the purpose of DNA transfer
Type 1 fimbriae Fimbriae in Enterobacteriaceae which bind specifically to mannose terminated glycoproteins on eucaryotic cell surfaces
Type 4 pili
Pili in certain Gram-positive and Gram-negative bacteria. In Pseudomonas, thought to play a role in adherence and biofilm formation

S-layer
Proteins that form the outermost cell envelope component of a broad spectrum of bacteria, enabling them to adhere to host cell membranes and environmental surfaces in order to colonize.
Glycocalyx A layer of exopolysaccharide fibers on the surface of bacterial cells which may be involved in adherence to a surface. Sometimes a general term for a capsule.
Capsule A detectable layer of polysaccharide (rarely polypeptide) on the surface of a bacterial cell which may mediate specific or nonspecific attachment
Lipopolysaccharide (LPS) A distinct cell wall component of the outer membrane of Gram-negative bacteria with the potential structural diversity to mediate specific adherence. Probably functions as an adhesin
Teichoic acids and lipoteichoic acids (LTA) Cell wall components of Gram-positive bacteria that may be involved in nonspecific or specific adherence

Specific Adherence of Bacteria to Cell and Tissue Surfaces

Several types of observations provide indirect evidence for specificity of adherence of bacteria to host cells or tissues:

1. Tissue tropism: particular bacteria are known to have an apparent preference for certain tissues over others, e.g. S. mutans is abundant in dental plaque but does not occur on epithelial surfaces of the tongue; the reverse is true for S. salivarius which is attached in high numbers to epithelial cells of the tongue but is absent in dental plaque.

2. Species specificity: certain pathogenic bacteria infect only certain species of animals, e.g. N. gonorrhoeae infections are limited to humans; Enteropathogenic E. coli K-88 infections are limited to pigs; E. coli CFA I and CFA II infect humans; E. coli K-99 strain infects calves.; Group A streptococcal infections occur only in humans. 

3. Genetic specificity within a species: certain strains or races within a species are genetically immune to a pathogen , e.g. Certain pigs are not susceptible to E. coli K-88 infections; Susceptibility to Plasmodium vivax infection (malaria) is dependent on the presence of the Duffy antigens on the host's redblood cells.

Although other explanations are possible, the above observations might be explained by the existence of specific interactions between microorganisms and eucaryotic tissue surfaces which allow microorganisms to become established on the surface.

Mechanisms of Adherence to Cell or Tissue Surfaces

The mechanisms for adherence may involve two steps:

1.  nonspecific adherence: reversible attachment of the bacterium to the eucaryotic surface (sometimes called "docking")

2. specific adherence: reversible permanent attachment of the microorganism to the surface (sometimes called "anchoring").

The usual situation is that reversible attachment precedes irreversible attachment but in some cases, the opposite situation occurs or specific adherence may never occur.

Nonspecific adherence involves nonspecific attractive forces which allow approach of the bacterium to the eucaryotic cell surface. Possible interactions and forces involved are:

1. hydrophobic interactions

2. electrostatic attractions

3. atomic and molecular vibrations resulting from fluctuating dipoles of similar frequencies

4. Brownian movement

5. recruitment and trapping by biofilm polymers interacting with the bacterial glycocalyx (capsule)

Specific adherence involves permanent formation of many specific lock-and-key bonds between complementary molecules on each cell surface. Complementary receptor and adhesin molecules must be accessible and arranged in such a way that many bonds form over the area of contact between the two cells. Once the bonds are formed, attachment under physiological conditions becomes virtually irreversible.

Specific adherence involves complementary chemical interactions between the host cell or tissue surface and the bacterial surface. In  the language of medical microbiologist, a bacterial "adhesin" attaches covalently to a host "receptor" so that the bacterium "docks" itself on the host surface. The adhesins of bacterial cells are chemical components of capsules, cell walls, pili or fimbriae. The host receptors are usually glycoproteins located on the cell membrane or tissue surface.

Several types of experiments  provide direct evidence that receptor and/or adhesin molecules mediate specificity of adherence of bacteria to host cells or tissues. These include:

1. The bacteria will bind isolated receptors or receptor analogs.

2. The isolated adhesins or adhesin analogs will bind to the eucaryotic cell surface.

3. Adhesion (of the bacterium to the eucaryotic cell surface) is inhibited by:

    a. isolated adhesin or receptor molecules

    b. adhesin or receptor analogs

    c. enzymes and chemicals that specifically destroy adhesins or receptors

    d. antibodies specific to surface components (i.e., adhesins or receptors)



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