Mechanisms of Bacterial Pathogenesis
Mechanisms of Bacterial Pathogenesis
Mechanisms of Bacterial Pathogenesis
Two broad qualities of pathogenic bacteria underlie the means by which they
cause disease
Exotoxins are released from bacterial cells and may act at tissue sites away
from the site of bacterial growth.
Some bacterial toxins may also act at the site of colonization and play a role in
invasion
Mechanisms of Bacterial Pathogenicity:
Entry sites: In human hosts the urogenital tract, the digestive tract, the
respiratory tract and the conjunctiva.
1. Tissue tropism: apparent preference for certain tissues over others, e.g.
Streptococcus mutans is abundant in dental plaque but not on epithelial surfaces of the
tongue.
Streptococcus salivarius high numbers to epithelial cells of the tongue but absent in
dental plaque.
E. Coli CFA I and CFA II infect humans; E. Coli K-99 strain infects calves.;
1. Hydrophobic interactions
2. Electrostatic attractions
4. Brownian movement
Specific adherence:
Invasins usually act at a short range (in the immediate vicinity of bacterial
growth) and may not actually kill cells as part of their range of activity;
exotoxins are often cytotoxic and may act at remote sites.
Exotoxins typically are more specific and more potent in their activity than
invasins.
INVASION:
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 relatively specific cytopathic
effect .
Pathogenic mycobacteria have a waxy cell wall that resists attack or digestion
by most tissue bactericides
Bacteria that readily attract phagocytes, and that are easily ingested and killed,
are generally unsuccessful as parasites
4. Hide the antigenic surface of the bacterial cell. Some pathogens can cover the
surface of the bacterial cell with a component which is seen as "self" by the host
phagocytes and immune system.
Phagocytes cannot recognize bacteria upon contact and the possibility of opsonization
by antibodies to enhance phagocytosis is minimized.
For example, pathogenic Staphylococcus aureus produces cell-bound
coagulase which clots fibrin on the bacterial surface. Treponema pallidum binds
fibronectin to its surface. Group A streptococci are able to synthesize a capsule
composed of hyaluronic acid.
Avoiding Contact with Phagocytes:
The environment of the phagocyte may be a protective one, protecting the bacteria
during the early stages of infection or until they develop a full complement of virulence
factors. The intracellular environment guards the bacteria against the activities of
extracellular bactericides, antibodies, drugs, etc.
Survival Inside of Phagocytes:
Little is known of how bacteria can resist phagocytic killing within the phagocytic
vacuole, but it may be due to the surface components of the bacteria or due to
extracellular substances that they produce which interfere with the mechanisms of
phagocytic killing.
Early escape from the phagosome vacuole is essential for growth and virulence of some
intracellular pathogens. This is a very clever strategy employed by the Rickettsi as
which produce a phospholipase enzyme that lyses the phagosome membrane within
thirty seconds of after ingestion.
Products of Bacteria that Kill or Damage Phagocytes:
One obvious strategy in defense against phagocytosis is direct attack by the bacteria
upon the professional phagocytes. Any of the substances that pathogens produce that
cause damage to phagocytes have been referred to as "aggressins". Most of these are
actually extracellular enzymes or toxins that kill phagocytes. Phagocytes may be killed
by a pathogen before or after ingestion.
Evading Complement:
Antibodies that are bound to bacterial surfaces will activate complement by the classical
pathway and bacterial polysaccharides activate complement by the alternative pathway.
Bacteria in serum and other tissues, especially Gram-negative bacteria, need protection from
the antimicrobial effects of complement before and during an immunological response.
One role of capsules in bacterial virulence is to protect the bacteria from complement
activation and the ensuing inflammatory response.
Polysaccharide capsules can hide bacterial components such as LPS or peptidoglycan which
can induce the alternate complement pathway. Some bacterial capsules are able to inhibit
formation of the C3b complex on their surfaces, thus avoiding C3b opsonization and
subsequent formation of C5b and the membrane attack complex (MAC) on the bacterial cell
surface. Capsules that contain sialic acid (a common component of host cell glycoproteins),
such as found in Neisseria meningitidis, have this effect.
Products of Bacteria that Kill or Damage Phagocytes:
Evading Complement:
LPS can be modified by pathogens in two ways that affects its interaction with
complement. First, by attachment of sialic acid residues to the LPS O antigen, a
bacterium can prevent the formation of C3 convertase just as capsules that contain
sialic acid can do so. Both Neisseria meningitidis and Haemophilus influenzae, which
cause bacterial meningitis, are able to covalently attach sialic acid residues to their O
antigens resulting in resistance to MAC.
Second, LPS with long, intact O antigen side-chains can prevent effective MAC killing.
Apparently the MAC complex is held too far from the vulnerable outer membrane to
be effective.
Bacteria that are not killed and lysed in serum by the complement MAC are said to be
serum resistant. Many of the Gram-negative bacteria that cause systemic infections,
(bacteremia or septicemia) are serum resistant. Gram-positive bacteria are naturally
serum-resistant since their cells are not enclosed in an outer membrane.
Products of Bacteria that Kill or Damage Phagocytes:
Evading Complement:
Other ways that pathogens are able to inhibit the activity of complement is to destroy
one or more of the components of complement. Pseudomonas aeruginosa produces an
extracellular elastase enzyme that inactivates components of complement.
Once the epithelial surfaces have been penetrated, however, the major host defenses of
inflammation, complement, phagocytosis, Antibody-mediated Immunity (AMI), and
Cell-mediated Immunity (CMI) are encountered. If there is a way for a pathogen to
successfully bypass or overcome these host defenses, then some bacterial pathogen has
probably discovered it.
Bacteria evolve very rapidly in relation to their host, so that most of the feasible anti-
host strategies are likely to have been tried out and exploited.
Products of Bacteria that Kill or Damage Phagocytes:
Ability to defeat the immune defenses may play a major role in the virulence of a
bacterium and in the pathology of disease. Several strategic bacterial defenses are
described below.
1.Fetal exposure to Ag
Antigenic Disguise :
Bacteria may be able to coat themselves with host proteins (fibrin, fibronectin, antibody
molecules) or with host polysaccharides (sialic acid, hyaluronic acid) so that they are
able to hide their own antigenic surface components from the immunological system.
Immunosuppression:
Some pathogens (mainly viruses and protozoa, rarely bacteria) cause
immunosuppression in the infected host. This means that the host shows depressed
immune responses to antigens in general, including those of the infecting pathogen.
Suppressed immune responses are occasionally observed during chronic bacterial
infections such as leprosy and tuberculosis.
For example, small amounts of endotoxin (LPS) may be released into surrounding
fluids by Gram-negative bacteria.
Antigenic Variation:
One way bacteria can avoid forces of the immune response is by periodically changing
antigens, i.e., undergoing antigenic variation. Some bacteria avoid the host antibody
response by changing from one type of fimbriae to another, by switching fimbrial tips.
This makes the original AMI response obsolete by using new fimbriae that do not bind
the previous antibodies. Pathogenic bacteria can vary (change) other surface proteins
that are the targets of antibodies. Antigenic variation is prevalent among pathogenic
viruses as well.
Changing antigens during the course of an infection:
Antigens may vary or change within the host during the course of an infection, or
alternatively antigens may vary among multiple strains (antigenic types) of a parasite in
the population. Antigenic variation is an important mechanism used by pathogenic
microorganisms for escaping the neutralizing activities of antibodies.