Mechanisms of Bacterial Pathogenicity (page 4)
(This chapter has 8 pages)
© Kenneth Todar, PhD
The invasion of a host by a pathogen may be aided by the production
of bacterial extracellular substances which act against the host by
down primary or secondary defenses of the body. Medical microbiologists
have long referred to these substances as invasins. Most
proteins (enzymes) that act locally to damage host cells and/or have
immediate effect of facilitating the growth and spread of the pathogen.
The damage to the host as a result of this invasive activity may become
part of the pathology of an infectious disease.
The extracellular proteins produced by bacteria which promote their
invasion are not clearly distinguished from some extracellular protein
toxins ("exotoxins") which also damage the host. Invasins usually act
a short range (in the immediate vicinity of bacterial growth) and may
actually kill cells as part of their range of activity; exotoxins are
and may act at remote sites (removed from the site of bacterial
Also, exotoxins typically are more specific and more potent in their
than invasins. Even so, some classic exotoxins (e.g. diphtheria toxin,
anthrax toxin) may play some role in colonization or invasion in the
early stages of an
infection, and some invasins (e.g. staphylococcal leukocidin) have a
specific cytopathic effect.
A Survey of Bacterial Invasins
"Spreading Factors" is a descriptive term for a family of bacterial
that affect the physical properties of tissue matrices and
spaces, thereby promoting the spread of the pathogen.
Hyaluronidase. is the original spreading factor. It is
by streptococci. staphylococci, and clostridia. The enzyme attacks the
interstitial cement ("ground substance") of connective tissue by
Collagenase is produced by Clostridium histolyticum
perfringens. It breaks down collagen, the framework of muscles,
facilitates gas gangrene due to these organisms.
Neuraminidase is produced by intestinal pathogens such as Vibrio
cholerae and Shigella dysenteriae. It degrades neuraminic
(also called sialic acid), an intercellular cement of the epithelial
of the intestinal mucosa.
Streptokinase and staphylokinase are produced by
and staphylococci, respectively. Kinase enzymes convert inactive
to plasmin which digests fibrin and prevents clotting of the blood. The
relative absence of fibrin in spreading bacterial lesions allows more
diffusion of the infectious bacteria.
Enzymes that Cause Hemolysis and/or
These enzymes usually act on the animal cell membrane by insertion
the membrane (forming a pore that results in cell lysis), or by
attack on phospholipids, which destabilizes the membrane. They may be
to as lecithinases or phospholipases, and if they lyse
blood cells they are sometimes called hemolysins. Leukocidins,
produced by staphylococci and streptolysin produced by streptococci
specifically lyse phagocytes and their granules. These latter two
are also considered to be bacterial exotoxins.
Phospholipases, produced by Clostridium perfringens
alpha toxin), hydrolyze phospholipids in cell membranes by removal
polar head groups.
Lecithinases, also produced by Clostridium perfringens,
destroy lecithin (phosphatidylcholine) in cell membranes.
Hemolysins, notably produced by staphylococci (i.e.,
toxin), streptococci (i.e., streptolysin) and various clostridia, may
channel-forming proteins or phospholipases or lecithinases that destroy
red blood cells and other cells (i.e., phagocytes) by lysis.
Beta-hemolytic Streptococcus. This is the characteristic appearance of
a blood agar plate culture of the bacterium. Note the translucency
around the bacterial colonies, representing hemolysis of the red cells
in the culture medium due to production of a diffusible hemolysin
Coagulase, formed by Staphylococcus aureus, is a
and diffusible enzyme that converts fibrinogen to fibrin which causes
Coagulase activity is almost always associated with pathogenic S.
and almost never associated with nonpathogenic S. epidermidis,
has led to much speculation as to its role as a determinant of
Possibly, cell bound coagulase could provide an antigenic disguise if
clotted fibrin on the cell surface. Or a staphylococcal lesion encased
in fibrin (e.g. a boil or pimple) could make the bacterial cells
to phagocytes or tissue bactericides or even drugs which might be
to diffuse to their bacterial target.
Extracellular Digestive Enzymes
Heterotrophic bacteria, in general, produce a wide variety of
enzymes including proteases, lipases, glycohydrolases,
etc., which are not clearly shown to have a direct role in invasion or
pathogenesis. These enzymes presumably have other functions related to
bacterial nutrition or metabolism, but may aid in invasion either
Toxins With Short-Range Effects Related to
Bacterial protein toxins which have adenylate cyclase activity, are
thought to have immediate effects on host cells that promote bacterial
invasion. One component of the anthrax toxin (EF or Edema
is an adenylate cyclase that acts on nearby cells to cause
levels of cyclic AMP and disruption of cell permeability. One of the
of Bordetella pertussis, the agent of whooping cough, has
a similar effect. These toxins may contribute to invasion through their
effects on macrophages or lymphocytes in the vicinity which are
an essential role to contain the infection. For example, since they use
ATP as a substrate, they may deplete phagocyte reserves of energy
needed for ingestion. Edema is seen as a pathology because the increase
in cAMP in affected cells disrupts equilibrium.
Gelatinous edema seen in a cutaneous
anthrax lesion. CDC.
The following table summarizes the activities of many bacterial
that are noted for their contribution to bacterial invasion of tissues.
TABLE 3. SOME
PROTEINS THAT ARE CONSIDERED INVASINS
||Streptococci, staphylococci and clostridia
||Degrades hyaluronic of connective tissue
||Dissolves collagen framework of muscles
||Vibrio cholerae and Shigella
||Degrades neuraminic acid of intestinal mucosa
||Converts fibrinogen to fibrin which causes
||Staphylococci and streptococci
||Converts plasminogen to plasmin which digests
||Disrupts neutrophil membranes and causes
||Repels phagocytes and disrupts phagocyte
membrane and causes
of lysosomal granules
||Streptococci, staphylococci and
||Phospholipases or lecithinases that destroy
red blood cells
cells) by lysis
||Destroy lecithin in cell membranes
||Destroy phospholipids in cell membrane
||One component (EF) is an adenylate cyclase
of intracellular cyclic AMP
||One toxin component is an adenylate cyclase
that acts locally
an increase in intracellular cyclic AMP