The Bacterial Cell Pathogenesis

THE BACTERIAL CELL
PATHOGENESIS
Pathogenesis is a multi-factorial process which depends on the immune status of the host,
the nature of the species or strain (virulence factors) and the number of organisms in the
initial exposure.
A limited number of bacterial species are responsible for the majority of infectious
diseases in healthy individuals. Due to the success of vaccination, antibiotics, and
effective public health measures, until recently, epidemics were felt to be a thing of the
past. Due to the development of antibiotic resistant organisms, this situation is changing
rapidly.
All humans are infected with bacteria (the normal flora) living on their external surfaces
(including the skin, gut and lungs). We are constantly also exposed to bacteria (including
air, water, soil and food). Normally due to our host defenses most of these bacteria are
harmless. In compromised patients, whose defenses are weakened, these bacteria often
cause opportunistic infectious diseases when entering the bloodstream (after surgery,
catheterization or other treatment modalities). When initiated in the hospital, these
infectious diseases are referred to as nosocomial. Some common bacteria found in the
normal flora include Staphylococcus aureus, S. epidermidis and Propionibacterium acnes
(found on the skin) and Bacteroides and Enterobacteriaceae found in the intestine.
TRANSMISSION
Specific bacterial species (or strains within a species) initiate infection after being
transmitted by different routes to specific sites in the human body. For example, bacteria
are transmitted in airborne droplets to the respiratory tract, by ingestion of food or water
or by sexual contact.
ADHESION
Bacterial infections are usually initiated by adherence of the microbe to a specific
epithelial surface of the host. Otherwise the organism is removed e.g. by peristalsis and
defecation (from the gut) ciliary action, coughing and sneezing (from the respiratory tract)
or urination (from the urogenital tract). Adhesion is not non-specific "stickiness". Specific
interactions between external constituents on the bacterial cell (adhesins) and on the host
cell (receptors) occur i.e. an adhesin-receptor interaction.
PENETRATION AND SPREAD
Some bacterial pathogens reside on epithelial surfaces e.g. Vibrio cholerae. Other species
are able to penetrate these barriers but remain locally. Others pass into the bloodstream
or from there onto other systemic sites. This often occurs in the intestine, urinary tract
1
and respiratory tract, and much less commonly through the skin. For example, Shigella
penetrates by activating epithelial cells of the intestine to become endocytic; the Shigella
do not usually spread into the bloodstream. In other cases, bacteria (e.g. Salmonella
typhi) pass through epithelial cells into the bloodstream. Thus, invasion can refer to the
ability of an organism to enter a cell, although in some instances it can mean further
passage into the systemic vasculature. Borrelia burgdorferi is transmitted into the
bloodstream through the skin by a tick bite. Certain degradative exotoxins secreted by
some bacteria (e.g. hyaluronidase or collagenase) can loosen the connective tissue matrix
increasing the ease of passage of bacteria through these sites.
SURVIVAL IN THE HOST
Many bacterial pathogens are able to resist the cytotoxic action of plasma and other body
fluids involving antibody and complement (classical pathway) or complement alone
(alternate pathway) or lysozyme. Killing of extracellular pathogens largely occurs within
phagocytes after opsonization (by antibody and/or complement) and phagocytosis.
Circumvention of phagocytosis by extracellular pathogens is thus a major survival
mechanism. Capsules (many pathogens), protein A (S. aureus) and M protein (S.
pyogenes) function in this regard.
Intracellular pathogens (both obligate and facultative) must be able to avoid being killed
within phagolysozomes. This can occur from by-passing or lysing these vesicles and then
residing free in the cytoplasm. Alternatively, they can survive in phagosomes (fusion of
phagosomes with lysosomes may be inhibited or the organism may be resistant to
degradative enzymes if fusion with lysosomes occurs).
TISSUE INJURY
Bacteria cause tissue injury primarily by several distinct mechanisms involving:
Exotoxins
Endotoxins and non-specific immunity
Specific humoral and cell mediated immunity
Exotoxins
Many bacteria produce proteins (exotoxins) that modify, by enzymatic action, or otherwise
destroy certain cellular structures. Effects of exotoxins are usually seen acutely, since they
are sufficiently potent that serious effects (e.g. death) often result. Examples of this are
botulism, anthrax, cholera and diphtheria. If the host survives the acute infection,
neutralizing antibodies (anti-toxins) are often elicited that neutralize the affect of the
exotoxin.
Classes of exotoxins include:
Toxins that act on the extracellular matrix of connective tissue
e.g. Clostridium perfringens collagenase, Staphylococcus aureus hyaluronidase.
Toxins that have a cell binding "B" component and an active "A" enzymatic
component (A-B type toxins)
These include: a). cholera toxin, E. coli heat labile toxin, Pseudomonas aeruginosa and
diphtheria toxins, shiga and shiga-like (vero) toxins., botulinum toxin, tetanus toxin and
anthrax lethal toxin.
Membrane Damaging Toxins e.g. Staphylococcus aureus delta toxin
Toxins which act extracellularly. These include proteases, collagenases and
hyaluronidases. For example, Clostridium perfringens produces a potent collagenase,
whilst Staphylococcus aureus produces a hyaluronidase. Damage to the connective tissue
matrix (by hyaluronidase and collagenase) can "loosen up" the tissue fibers allowing the
organism to spread through the tissues more readily. Also included in this group is the
2
exfoliatin of Staphylococcus aureus which causes separation of the layers within the
epidermis and is the causative agent of scalded skin syndrome in the newborn.
Endotoxins
Despite the advances of the antibiotic era, around 200,000 patients will develop Gram
negative sepsis each year of whom around 25-40% will ultimately die of septic shock.
Septic shock involves hypotension (due to tissue pooling of fluids), disseminated
intravascular coagulation and fever and is often fatal from massive system failure. This
includes lack of effective oxygenation of sensitive tissues such as the brain. There is no
effective therapy to reverse the toxic activity of lipid A or peptidoglycan in patients.
Endotoxins are toxic components of the bacterial cell envelope. The classical and most
potent endotoxin is lipopolysaccharide. However, peptidoglycan displays many endotoxinlike properties. Certain peptidoglycans are poorly biodegradable and can cause chronic as
well as acute tissue injury. Endotoxins are "non-specific" inciters of inflammation. For
example, cells of the immune system and elsewhere are stimulated to release cytokines
(including interleukin 1 and tumor necrosis factor). Endotoxins also activate the alternate
complement pathway. The production of these cytokines results in attraction of
polymorphonuclear cells into affected tissues. PG and LPS and certain other cell wall
components (e.g. pneumococcal teichoic acid) are also activators of the alternate
complement cascade.
SOURCES: Dr. Alvin Fox, Donald Stahly, University of Iowa, Iowa City, Iowa and The
MicrobeLibrary
Microbiology and Immunology on line http://pathmicro.med.sc.edu/book/welcome.htm

The Bacterial Cell Pathogenesis

Uploaded by

Copyright:

Available Formats

The Bacterial Cell Pathogenesis

Uploaded by

Document Information

Original Description:

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

The Bacterial Cell Pathogenesis

Uploaded by

Copyright:

Available Formats

THE BACTERIAL CELL

You might also like