Colonization and Invasion by Bacterial Pathogens (page 2)
(This chapter has 4 pages)
© Kenneth Todar, PhD
Specific Adherence of Bacteria to Cell and
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
preference for certain tissues over others, e.g. S. mutans is
in dental plaque but does not occur on epithelial surfaces of the
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
certain species of animals, e.g. N. gonorrhoeae and Bordetella pertussis infections are
to humans; enteropathogenic E. coli K-88 infections are limited
to pigs; E. coli CFA I and CFA II infect humans; E. coli
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
within a species may be genetically immune to a pathogen, e.g. certain
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
be explained by the existence of specific interactions between
and eucaryotic tissue surfaces which allow microorganisms to become
on the surface.
Mechanisms of Adherence to Cell or Tissue
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
microorganism to the surface (sometimes called "anchoring").
The usual situation is that reversible attachment precedes
attachment but in some cases, the opposite situation occurs or specific
adherence may never occur.
Nonspecific adherence involves
attractive forces which allow approach of the bacterium to the
cell surface. Possible interactions and forces involved are:
1. hydrophobic interactions
2. electrostatic attractions
3. atomic and molecular vibrations resulting from fluctuating
of similar frequencies
4. Brownian movement
5. recruitment and trapping by biofilm polymers interacting with the
bacterial glycocalyx (capsule)
Specific adherence involves
formation of many specific lock-and-key bonds between complementary
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,
under physiological conditions becomes virtually irreversible.
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
and/or adhesin molecules mediate specificity of adherence of
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
3. Adhesion (of the bacterium to the eucaryotic cell surface) is
a. isolated adhesin or receptor molecules
b. adhesin or receptor analogs
c. enzymes and chemicals that specifically destroy adhesins or
d. antibodies specific to surface components (i.e., adhesins or
Some Specific Bacterial Adhesins and their
The adhesins of E. coli are their common
A single strain of E. coli is known to be able to express
distinct types of fimbriae encoded by distinct regions of the
or plasmids. This genetic diversity permits an organism to adapt to its
changing environment and exploit new opportunities presented by
host surfaces. Many of the adhesive fimbriae of E. coli have
evolved from fimbrial ancestors resembling Type-I and Type IV pili.
Type-I fimbriae enable E. coli to bind to D-mannose residues
on eucaryotic cell surfaces. Type-I fimbriae are said to be
since exogenous mannose blocks binding to receptors on red blood cells.
Although the primary 17kDa fimbrial subunit is the major protein
of Type-1 fimbriae, the mannose-binding site is not located here, but
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
For example, tip proteins on pyelonephritis-associated (pap) pili
a galactose-galactose disaccharide, while tip proteins on S-fimbriae
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
at or near its amino terminus. These "N-methylphenylalanine pili" have
as virulence determinants in pathogenesis of Pseudomonas aeruginosa
lung infection in cystic fibrosis patients. These type of fimbriae
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
Gram stain of Neisseria gonorrhoeae, the
agent of the STD gonorrhea. The bacteria are seen as pairs of
cocci (diplococci) in association with host pmn's (polymorphonuclear
leukocytes). Gonorrhea is the second most prevalent bacterial STD in
behind chlamydia. The bacterium has multiple determinants of virulence
including the ability to attach to and enter host cells, resist
phagocytic killing and produce endotoxins which eventually lead to an
intense inflammatory response. CDC.
The adhesins of Streptococcus pyogenes are
In 1972, Gibbons and his colleagues demonstrated that attachment of
to the oral mucosa of mice is dependent on M protein. Olfek and Beachey
argued that lipoteichoic acid (LTA), rather than M protein, was
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
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
in 1998, M proteins M1 and M3 were also found to bind to fibronectin.
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
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
the bacterial surface. Apparently, S. aureus and Group A
use different mechanisms but adhere to the same receptor on epithelial
Treponema pallidum has three related surface adhesins
(P1, P2 and P3), which bind to a four-amino acid sequence
of the cell-binding domain of fibronectin. It is not clear if T.
uses fibronectin to attach to host surfaces or coats itself with
to avoid host defenses (phagocytes and immune responses).
Treponema pallidum, the spirochete
that causes syphilis. Silver stain. CDC.
TABLE 2. EXAMPLES OF SPECIFIC
OF BACTERIA TO HOST CELL OR TISSUE SURFACES
||Amino terminus of fibronectin
||Pellicle of tooth
||Buccal epithelium of tongue
||Amino terminus of fibronectin
||Type IV pili (N-methylphenyl- alanine pili)
|Enterotoxigenic E. coli
|Uropathogenic E. coli
||Type I fimbriae
|Uropathogenic E. coli
||Globobiose linked to ceramide lipid
||Upper urinary tract
||Fimbriae ("filamentous hemagglutinin")
||Galactose on sulfated glycolipids
|Fucose and mannose carbohydrate
||Peptide in outer membrane
||Surface protein (fibronectin)
||Conjunctival or urethral epithelium
||Conjunctivitis or urethritis