Pathogenesis of

Bacterial Infection

Ivy June T. Minerva, MD

 Bacterial
Infection

• initiation of the infectious process

• mechanisms that leads to the development of the

signs and symptoms of the disease.
 Terms

• Adherence (adhesion, attachment): The process by which

bacteria stick to the surfaces of host cells.

• Carrier - Human or animal carrier; Asymptomatic but can

transfer infection to a susceptible person
 Terms

• Infection - Multiplication of an infectious agent /

pathogenic bacteria within the body

• Invasion - the property of microorganisms to enter the

body (host cell or tissue) and spread disease or
infection.
 Terms

• Pathogen - a microorganism that is known to cause a

disease

• Non-pathogen - a microorganism that does not cause

disease; may be part of the normal flora.
 Terms

• Opportunistic pathogen - a microorganism that is capable

of producing the disease only when the host cell’s
resistance is impaired (immunocompromised).

• Pathogenecity - the ability / potential of the microorganism

to cause disease;
 Terms

• Toxigenicity - the ability of the microorganism to produce

toxins contributing to pathogenicity.

• Virulence - quantitative ability of an agent to cause

disease. Involves adherence, invasion, and toxigenicity
 Koch’s Postulate

• Robert Koch, 1884

• Proposed a series of statements that have been

applied to specific (or most) of the bacterial species
and how they produce disease.
 Koch’s Postulates
1. The microorganism should be found in all cases of the
disease in question. The distribution in the body should be in
accordance with the lesions observed.

2. The microorganism should be grown in pure culture in vitro

(or outside the body of the host) for several generations.

3. When such a pure culture is inoculated into susceptible

animal species, the typical disease must result.

4. The microorganism must again be isolated from the le-

sions of such experimentally produced disease.
 Exceptions to Koch’s
postulate

• Treponema pallidum (Syphilis)

• Mycobacterium leprae (Leprosy)

• both cannot be grown in artificial medium (in vitro)

but through live animal inoculation (in vivo)
• Koch’s postulates allowed the classification of
bacteria as either pathogen, opportunistic pathogens
or non pathogens.

• Molecular genetics

• PCR (polymerase chain reaction)

• able to amplify (replicate) microorganism specific

nucleic acid sequence from host tissues or fluids
and identify disease cause.
PCR
Transmission of Infection
• Bacteria adapt to the environment

• Bacteria ensures their survival and possibility of transmission.

• Eg. Salmonella and Campylobacter - exists primarily in

animals but can incidentally infect humans.

• Some are inadvertent (not part of the their normal life cycle)
but cause severe disease when they adapt to human form

• Yersinia pestis (plague) - well established life cycle in

rodents and fleas — > human contact.
Transmission of Infection
• Clinical manifestation of disease produced by
microorganisms often promote transmission of the
agents

• Eg. Vibrio cholerae — causes Cholera; from

ingestion contaminated fresh water, drinking water
and seafood; causes voluminous diarrhea

• excreted water products may continually

contaminate food within the community
•
Portals of Entry
Sites where mucous membranes meet with the skin:

• Respiratory

• GIT

• GUT

• Abnormal areas of

• Mucous membrane & skin

• (cuts, burns, traumatic injuries)

 The Infectious Process
• 1. attachment of bacteria (epithelial cells)

• Primary site of infection

• Multiply and spread  tissues or via bloodstream and lymphatics

• Infection can be transient or persistent.

• Eg. Streptococcus pneumoniae (seen 5 - 40% in some nasopharynx -

when aspirated into the lungs, may cause infection developing into the
alveoli causing Pneumonia)

• May enter the lymphatics —>bloodstream causing bacteremia

• May spread to CSF, heart and joints causing meningitis, endocarditis.

• Transfer of extrachromosomal genetic elements for
exchange of genetic information

• phages and plasmids

• results in transfer of virulence factors

Pathogenicity Islands (PAIs)
• large organized groups of genes (10 - 200 kb)

• one or more virulence genes

• present in the genome of pathogenic members of a

species but absent in the non-pathogenic members

• different content as to purine and pyrimidine bases

• associated with mobile genetic elements

• genetic instability
Bacterial Virulence Factors
1. Adherence Factors

2. Invasion of Host Cells

3. Toxins

4. Enzymes

5. Antiphagocytic Factors

6. Intracellular Pathogenecity

7. Antigenic Heterogeneity

8. Requirement for Iron

 Adherence Factors
• adherence of a bacterial cell once it enters the body
of the host. (or they may be swept away by mucus
and other fluids)

• followed by development of micro colonies and

subsequent steps in the pathogenesis

• Pili - hairlike appendages that extend from the

bacterial cell surface and help mediate adherence of
the bacteria to host cell surfaces.
 Adherence Factor
• Escherichia coli

• Type 1 Pili - adherence to epithelial cell receptors (GUT)

• P pili - attached to blood cell antigen causing UTI

• Group A Streptococci (Streptococcus pyogenes)

• Fimbriae with Protein F and M Protein, and lipotechoic acid

• Lipotechoic acid and Protein F cause adherence to buccal

epithelial cells.

• M protein acts as antiphagocytic factor.

Adherence
 Invasion of Host Cells and
Tissues
• Central to the infectious process

• Invade through junctions of the host cell (Salmonella)

• Other bacteria invade epithelial cells then tissues (Neisseria and

Chlamydia)

• Bacteria may remain in a vacuole enclosed by host cell

membrane

• Vacuole may dissolve and bacteria may be dispersed in the

cytoplasm

• Bacterial may multiply inside host cells.

 Invasion of Host Cells and
Tissues
• HeLa cells - cervical cancer cells experimentally infected with
Shigella (bacteria causing diarrheal disease Shigellosis)

• Adherence of Shigella noted with formation of pseudopods to engulf

the bacteria

• Shigella inside HeLa cells were released and escaped from the
phagocytic vacuole and multiplied inside the cytoplasm

• Actin polymerization propels Shigella from one cell to another

• May multiply inside macrophages and eventually lyse upon release.

Invasion
 Toxins (Exotoxins and
Endotoxins)
A. Exotoxins

B. Exotoxins associated with diarrheal diseases and

food poisoning

C. LPS of gram negative bacteria

D. Peptidoglycan of gram positive bacteria

 Exotoxins Endotoxins
Excreted by living cells, high concentration in liquid Integral part of the gram negative bacterial cell wall;
medium released upon bacterial death.

Produced by both gram (-) and (+) bacteria Produced by gram (-) bacteria only.

Relatively unstable, destroyed by heat Relatively stable, can withstand temperature (> 60
(>60 C) C) without loss of toxicity

Highly antigenic Weakly immunogenic

Can be converted to toxoids Cannot be converted to toxoids

Highly toxic, fatal in microgram quantities or less Moderately toxic, fatal in hundreds of micrograms

Usually bind to specific receptors to cells No specific receptors found on cells

Usually does not produce fever in the host Produce fever through the release of IL 1

Controlled by extrachromosomal genes (phages

Directed by own chromosomal genes
and plasmids)
 Exotoxin
• Clostridium tetani (Tetanus)

• anaerobic Gram (+) rod

• Contaminates wounds

• Toxin - Tetanospasmin; binds to receptors of the presynaptic

neuron

• retrograde migrations to the spinal cord and brain stem

• Release of inhibitory neurotransmitters is blocked and the

neurons are not inhibited —> Spastic paralysis
 Clostridium tetani

• Toxoids - made from toxins modified to be no longer

toxic

• Composed of A and B Subunits

• A - toxic activity

• B - mediates adherence
Tetanus
 Clostridium botulinum
• Found in soil and water; food (canned and vacuum)

• Toxins (type A, B, E) - most commonly associated with human

disease

• Botulinum toxin - most potent toxin known to man

• absorbed from the GUT and binds to receptors of the pre-synaptic

membrane

• inhibits the release of Ach at the synapse

• lack of muscle contraction and paralysis

• Respiratory muscles of breathing — leads to death

Botulism
Corynebacterium diphtheriae

• Diphtheria

• Gm (+) rod

• mucous membrane (URT)

• carry bacteriophage to produce diphtheria toxin

Diphtheria
 Clostridium perfringens
• Gas gangrene - distention of tissue by gas formed by
carbohydrates; necrotizing effect.

• Food poisoning

• introduced into the wound by contamination with soil /

feces.

• Necrotic tissue, spores germinate and vegetative cells

produce toxins

• Lecithinase (alpha toxin)

Gas Gangrene
 Staphylococcus aureus

• Toxic Shock Syndrome Toxin - 1 (TSST - 1)

• shock, high fever, red rash with desquamation

(peels off)

• implicated to grow on mucous membranes (eg.

menstruation)
Toxic Shock Syndrome
 Exotoxins Associated with Diarrheal
Disease and Food Poisoning
• Vibrio cholerae

• Cholera; penetrates the intestinal mucosa

• produces enterotoxin two subunits A and B

• rapid secretion of electrolytes into the small bowel lumen

• impairment of Na and Cl absorption leading to life

threatening massive diarrhea

• fluid loss, acid-base and electrolyte imbalance

 Staphylococcus aureus
• Staphylococcal enterotoxin - super antigen

• Growing on meat, dairy products and food

• Absorbed in the GUT to stimulate neural receptors

• Stimulation of vomitting

• Staphylococcal food poisoning (most common

cause of food poisoning)
 Lipopolysaccharide of
Gram (-) Bacteria

• LPS (endotoxin) are derived from cell wall

• often liberated where bacteria becomes lysed

• heat - stable
LPS of Gram (-) Bacteria
• Pathophysiologic effects (except for Bacteroides)

• Bloodstream

• Fever

• Leukopenia (then leukocytosis)

• Hypoglycemia

• Hypotension - widespread arteriolar and ventral constriction

• Dilatation of vessels, vascular permeability, decrease in venous

return, lowered cardiac output→
LPS of Gram (-) Bacteria
• DIC (Disseminated Intravascular Coagulation)

• frequent complication of LPS (Gram (-)

bacteremia

• activates the clotting system

• fibrinogen to fibrin

• platelets adhere to the vascular endothelium and

occlusion of small blood vessels.
 Peptidoglycan of Gram (+)
Bacteria

• Same but less potent than LPS

 Enzymes

• Tissue degrading enzymes

• IgA1 Proteases
Tissue Degrading Enzymes
1. Lecithinase - C. perfringens

2. Collagenase - C. perfringens; degrades collagen (major

protein of fibrous connective tissue and promotes
spread of infection)

3. Coagulase - S. aureus; contributes to formation of fibrin

walls around staphylococcus lesions

4. Hyaluronidase - hydrolyzes hyaluronic acid (ground

substance) of connective tissues; spread of bacteria
within the tissues.
Tissue Degrading Enzymes
5. Streptokinase (Fibrinolysin) - activates proteolytic enzyme
of plasma; dissolves fibrin clots of coagulated plasma; spread
of streptococci to tissue.

6. Cytolysin - cell lysis; Hemolysin (RBC); Leukocidin (WBC)

Eg. Streptococci

Streptolysin ‘O’ - hemolytic for RBC

Streptolysin ’S’ - non - antigenic

 IgA1 proteases

• IgA - main antibody found in mucous membranes

• Some bacteria produce enzymes that attack IgA

• Eliminates protection of the host by the antibody

• N. gonorrheae, N. meningitidis, H. influenzae, S.

pneumoniae
 Antiphagocytic Factors
• Pathogens that evade phagocytosis or leukocyte
antimicrobial mechanisms

• Bacteria of many types or strains; not all types may

be protected

• S. aureus - Protein A

• S. pneumoniae and N. meningitidis -

polysaccharide capsules
Antiphagocytic Factors
 Antigenic Heterogeneity
• Surface structures of bacteria used as part of a serologic
classification system

• E.g Salmonella

• 200+ types based on ‘O’ (LPS) and ‘H’ (flagellum)

antigen.

• E. coli

• 100+ E. coli (K) capsule antigen types

• 150+ ‘O’ (LPS) types.

 Requirement for Iron

• Bacteria needs iron to grow

• Humans (and animals) have an abundant amount of

iron

• Iron assimilation
 Bacterial Biofilms

• Biofilms - aggregate of interactive bacteria attached to a solid

surface or to each other and encased in an extra polysaccharide
matrix

• forms a shiny coat on solid surfaces and occur throughout nature

• important in infections that are difficult to treat

• S. aureus, S. epidermidis

• catheters, contact lenses, artificial heart valves, etc.

 Bacterial Biofilms
• Initial step - colonisation of the surface

• Uses flagella to move and colonize

• Uses pili to create clumps.