Specific Adherence of Bacteria to Cell and Tissue Surfaces

Several types of observations have provided 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. Corynebacterium diphtheriae colonizes exclusively in the throat.

2. Species specificity. Certain pathogenic bacteria infect only certain species of animals, e.g. N. gonorrhoeae and Bordetella pertussis 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 strains infect calves.; Group A streptococcal infections occur only in humans. In addition, certain indigenous species and symbionts are quite specific in their associations with specific animal hosts.

3. Genetic specificity within a species: certain strains or races within a species may be genetically immune to a pathogen, e.g. certain pigs are not susceptible to E. coli K-88 infections; males are not susceptible to mastitis; females are not susceptible to orchitis; A percentage of females are not susceptible to urinary tract infection (UTI) caused by E. coli.

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: irreversible 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)

Type-I fimbriae enable E. coli to bind to D-mannose residues on eucaryotic cell surfaces. Type-I fimbriae are said to be "mannose-sensitive" since exogenous mannose blocks binding to receptors on red blood cells. Although the primary 17kDa fimbrial subunit is the major protein component of Type-1 fimbriae, the mannose-binding site is not located here, but resides in a minor protein (28-31kDa) located at the tips or inserted along the length of the fimbriae. By genetically varying the minor "tip protein" adhesin, the organisms can gain ability to adhere to different receptors. For example, tip proteins on pyelonephritis-associated (pap) pili recognize a galactose-galactose disaccharide, while tip proteins on S-fimbriae recognize sialic acid. S fimbriae are able to recognize receptor molecules containing sialic acid and are produced by pathogenic E. coli strains causing urinary tract infection.

Pseudomonas, Vibrio and Neisseria possess Type IV pili that contain a protein subunit with a methylated amino acid, often phenylalanine, at or near its amino terminus. These "N-methylphenylalanine pili" have been established as virulence determinants in pathogenesis of Pseudomonas aeruginosa lung infection in cystic fibrosis patients. These type of fimbriae occur in Neisseria gonorrhoeae and their receptor is thought to be an oligosaccharide. Type IV pili are the tcp (toxin coregulated pili) fimbriae used in attachment of Vibrio cholerae to the gastrointestinal epithelium.

The adhesins of Streptococcus pyogenes are controversial.  In 1972, Gibbons and his colleagues demonstrated that attachment of streptococci to the oral mucosa of mice is dependent on M protein. Olfek and Beachey argued that lipoteichoic acid (LTA), rather than M protein, was responsible for streptococcal adherence to buccal epithelial cells. In 1996, Hasty and Courtney proposed a two-step model of attachment that involved both M protein and teichoic acids.  They suggested that LTA loosely tethers streptococci to epithelial cells, and then M protein secures a firmer, irreversible association. In 1992, protein F was discovered and found to be a fibronectin binding protein. More recently, in 1998, M proteins M1 and M3 were also found to bind to fibronectin. Apparently, S. pyogenes produces multiple adhesins with varied specificities.

Electron micrograph of Streptococcus pyogenes (Group A strep) by Maria Fazio and Vincent A. Fischetti,Ph.D. with permission. The Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University. The cell surface fibrils, that consist primarily of M protein, are clearly evident.  The M protein has several possible roles in virulence: it is involved in adherence, resistance to phagocytosis, and in antigenic variation of the pathogen.

Staphylococcus aureus also binds to the amino terminus of fibronectin by means of a fibronectin-binding protein which occurs on the bacterial surface. Apparently, S. aureus and Group A streptococci use different mechanisms but adhere to the same receptor on epithelial surfaces.

Treponema pallidum has three related surface adhesins (P1, P2 and P3), which bind to a four-amino acid sequence (Arg-Gly-Asp-Ser) of the cell-binding domain of fibronectin. It is not clear if T. pallidum uses fibronectin to attach to host surfaces or coats itself with fibronectin to avoid host defenses (phagocytes and immune responses).