PATHOGENESIS OF BACTERIA

• Definitions:

• The term pathogen means microbe capable of

causing disease, in immunocompetent people.
• Opportunistic pathogen means microbe that
is capable of causing disease only in
immunocompromised people.
• Virulence

• The quantitative ability of an agent to cause

disease.
• It is a measure of a microbe's ability to cause
disease i.e. a highly virulent microbe requires
fewer organisms to cause disease than a less
virulent one.
• Toxigenicity:

• The ability of a microorganism to produce a

toxin that contributes to the development of
disease.
• Infection:

• Invasion and multiplication of an infectious

agent within the body.
• Invasion: The process whereby bacteria,
animal parasites, fungi, and viruses enter host
cells or tissues and spread in the body.
• Communicable diseases: they spread from
person to person. Many but not all infections are
communicable.
• Three epidemiologic terms are used to describe
infections:
• Endemic infections are those that occur at a
persistent, usually low level in a certain area.
• Epidemics are those infections that occur at a
much higher rate than usual.
• Pandemics are those infections that spread
rapidly over large areas of the globe.
• Mechanisms of Bacterial Infections:

• Bacteria cause disease by two major

mechanisms:

1. Toxin production

2.Invasion and inflammation.

• Toxins fall into two general categories:

A. Exotoxins

B. Endotoxins.
• Exotoxins are polypeptides released by the cell,

while endotoxins are lipopolysaccharides (LPS)

and are present as an integral part of the cell

wall.

• Endotoxins occur only in gram-negative bacteria

and are not actively released from the cell.

• Both exotoxins and endotoxins by themselves
can cause symptoms; the presence of the
bacteria in the host is not required.
• Invasive bacteria, on the other hand, grow to
large numbers locally and induce an
inflammatory response.
• Exotoxins are among the most toxic substances
known.
• Many exotoxins have an A (or active) subunit

and the B (or binding) subunit

• A subunit possesses the toxic activity, while B
subunit is responsible for binding the exotoxin
to specific receptors on the membrane of the
human cell
• When treated with formaldehyde (or acid

or heat), the exotoxin polypeptides are

converted into toxoids, which are used in
protective vaccines.
• Some important toxins include diphtheria toxin,
tetanus toxin and botulinum toxin.
• Endotoxins are integral parts of the cell walls of
both gram-negative rods and cocci.
• Endotoxins are lipopolysaccharides (LPS).

• The toxicity of endotoxins is low in comparison

with that of exotoxins.
• All endotoxins produce the same generalized
effects of fever and shock (Septic shock).
• Endotoxins are weakly antigenic.

• Endotoxins are present in outer cytoplasmic

membrane of the cell wall of gram negative
bacteria.
 Comparison of properties
Property Exotoxin Endotoxin

Source Certain species of gram-positive Cell wall of gram-negative

and gram-negative bacteria bacteria
Secreted from cell Yes No

Chemistry Polypeptide Lipopolysaccharide

Location of genes Plasmid or bacteriophage Bacterial chromosome

Toxicity High Low

Clinical effects Various effects Fever, shock

Mode of action Various modes Includes TNF and

interleukin-1
Antigenecity Highly antigenic Weakly antigenic

Toxoids used as vaccines No toxoid formed. No

Vaccines
vaccine found
Stability Destroyed at 60 0C Stable at 100 0C for 1 hour
• Stages of Bacterial Pathogenesis

1. Transmission from an external source into the

portal of entry

2. Evasion of primary host defenses such as skin

or stomach acid.

3. Adherence to mucous membranes.

4. Colonization by growth of the bacteria at the
site of adherence.

5. Disease symptoms caused by toxin production

or invasion

6. Host responses

7. Progression or resolution of the disease

• Determinants of Bacterial Pathogenesis:

1. Transmission:
• The modes of transmission of microbes include
both human-to-human and nonhuman-to-
human processes.
• Transmission from mother to child is called
vertical transmission while from person to
person is called horizontal.
• The three modes by which organisms are
transmitted vertically are across the
placenta, within the birth canal during
birth, and via breast milk from mother to
offspring.

2.Adherence to Cell Surfaces:

• Pili are the main mechanism by which
bacteria adhere to human cells.
• E.g. the pili of Neisseria gonorrhoeae and E. coli
mediate attachment to the urinary tract
epithelium.
• Glycocalyx is a polysaccharide "slime layer" that
mediates strong adherence to certain
structures such as heart valves, prosthetic
implants, and catheters.
• Similarly glycocalyx of Staphylococcus
epidermidis and certain viridans streptococci
help them to adhere to the endothelium of
heart valves.

3. Invasion, Inflammation, & Intracellular

Survival:
• One of the two main mechanisms by which
bacteria cause disease is invasion of tissue
followed by inflammation.
• Bacteria achieve this through production of
different enzymes like
• Collagenase. It degrades collagen allowing the
bacteria to spread through subcutaneous tissue
• Coagulase is produced by Staph.aureus and
accelerates the formation of a fibrin clot
from fibrinogen (this clot may protect the

bacteria from phagocytosis by walling off

the infected area and by coating the

organisms with a layer of fibrin)

3. Hyaluronidase. It degrades hyaluronic acid
allowing the bacteria to spread through
subcutaneous tissue

4. IgA protease, It degrades the secretory antibody

IgA.
• Bacteria can evade our host defenses by a
process called intracellular survival (i.e.,
bacteria that can live within cells are protected
from attack by macrophages and neutrophils).