PATHOGENESIS OF BACTERIAL INFECTION

GLOSSARY Jawetz Medical Microbiology, 26th Ed., pp. 149-150

Characteristics of Pathogenic Bacteria:
1. Transmissibility
2. Adherence to host cells
3. Persistence
4. Invasion of host cells and tissues
5. Toxigenicity
6. Ability to evade or survive the hosts immune system
Identifying Bacteria that Cause Disease
1. KOCHS POSTULATES (1884)
2. MOLECULAR KOCHS POSTULATES
3. MOLECULAR GUIDELINES FOR ESTABLISHING MICROBIAL DISEASE
CAUSATION
VIRULENCE
Quantitative measure of pathogenicity
Measured by the number of organisms required to cause disease
LD50 (50% lethal dose)- # of organisms needed to kill half of the hosts
ID50 (50% infectious dose)- # of organisms needed to cause infection in
half of
the hosts
Bacteria cause disease by:
1. Toxin Production
2. Invasion And Inflammation
3. Immunopathogenesis
Types of Bacterial Infection:
EPIDEMIC occurs much more frequently than usual
PANDEMIC worldwide distribution
ENDEMIC constantly present at a low level in a specific population
INAPPARENT/SUBCLINICAL detected only by demonstrating a rise in antibody
titer or by isolating the organism
LATENT STATE reactivation of the growth of the organism and recurrence of
symptoms may occur
CHRONIC CARRIER STATE organisms continue to grow with or without producing
symptoms in the host
STAGES
1.
2.
3.
4.
5.

OF BACTERIAL PATHOGENESIS:
TRANSMISSION from an external source into the portal of entry
EVASION of primary host defenses (skin, stomach acid)
ADHERENCE to mucous membranes usually by bacterial pili
COLONIZATION by growth of the bacteria at the site of adherence
DISEASE SYMPTOMS caused by toxin production or invasion accompanied by
inflammation
6. HOST RESPONSES (nonspecific, specific)
7. PROGRESSION or RESOLUTION of the disease

GENOMICS & BACTERIAL PATHOGENICITY

Mechanisms used by bacteria to transmit virulence genes from one to another:
1. Transformation- DNA from one organism is released into the
environment and is taken up by a different organism that is capable of
recognizing and binding DNA
2. Mobile genetic elements- plasmids, transposons, bacteriophages
VIRULENCE FACTORS ENCODED BY GENES ON MOBILE GENETIC ELEMENTS
(Table 9-2, p153)
PATHOGENICITY ISLANDS (PAIs)
Large group of genes that are associated with pathogenicity located on bacterial
chromosomes; 10-200 kb
Properties:
1. > 1 virulence genes
2. present in the genome of pathogenic members of a species, absent in
nonpathogenic members

3.
4.
5.
6.
7.
8.

large
different guanine + cytosine content (G+C) than the rest of the bacterial genome
commonly associated with tRNA genes
often found with parts of the genome associated with mobile genetic elements
often have genetic instability
often represent mosaic structures with components acquired at different times

DETERMINANTS OF BACTERIAL PATHOGENESIS

I.
TRANSMISSION
II.
ADHERENCE TO CELL SURFACES
III.
INVASION, INFLAMMATION & INTRACELLULAR SURVIVAL
IV.
TOXIN PRODUCTION
V.
IMMUNOPATHOGENESIS
TRANSMISSION
An understanding of the mode of transmission of bacteria and other
infectious agents is important because interrupting the chain of
transmission is an excellent way to prevent infectious diseases.
IMPORTANT MODES OF TRANSMISSION
Mode of
Transmission
I. HUMAN TO
HUMAN
A. Direct
Contact
B. No direct
contact
C.
Transplacental
D. Blood-borne
II. NONHUMAN
TO
HUMAN
A. Soil Source
B. Water Source
C. Animal Source
1. Directly
2. Via insect
vector
3. Via
animal
excreta
D. Fomite
Source

Clinical
Example

Gonorrhea
Dysentery
Congenital
syphilis
Syphilis

Intimate contact (sexual or passage through birth

canal)
Fecal-oral (excreted in human feces, then ingested in
food or water)
Bacteria cross the placenta and infect the fetus
Transfused blood or IV drug use can transmit
bacteria and viruses

Tetanus
Legionnaires
Disease

Spores in soil enter wound in skin

Bacteria in water aerosol are inhaled into lungs

Cat-scratch
Fever
Lyme Disease

Bacteria enter in cat scratch

Bacteria enter in tick bite

HUS by E. coli
0-157
Staphylococcal
skin infection

Bacteria in cattle feces are ingested in undercooked

hamburger
Bacteria on an object (towel) are transferred onto the
skin

VERTICAL TRANSMISSION from mother to offspring

Within birth canal/ at
the time of birth

Breast milk

Transplacental

Streptococcus agalactiae
(Group B streptococci)

Neonatal sepsis and meningitis

Escherichia coli
Chlamydia trachomatis
Neisseria gonorrhoeae

Neonatal sepsis and meningitis

Conjunctivitis and pneumonia
Conjunctivitis

Herpes simplex type-2

Skin, CNS, disseminated infection

(sepsis)
Hepatitis B
Asymptomatic infection

Hepatitis B virus
Human immune-deficiency
virus
Candida albicans
Staphylococcus aureus
Cytomegalovirus
Human T-cell leukemia
virus
Treponema pallidum

Thrush
Oral or skin infections
Asymptomatic infection
Asymptomatic infection
Congenital syphilis

Listeria monocytogenes
Cytomegalovirus

Neonatal sepsis and meningitis

Congenital abnormalities

Parvovirus
Toxoplasma gondii

Hydrops fetalis
Toxoplasmosis

IMPORTANT
1.
2.
3.
4.

PORTALS OF ENTRY
respiratory tract(upper and lower airways)
GIT (primarily mouth)
genital tract
urinary tract

Portal of
Entry
Respiratory
Tract

GIT

Skin

Pathogen

Disease

Streptococcus
pneumoniae
Neisseria
meningitides
Haemophilus
influenza
Mycobacterium
tuberculosis
Influenza virus
Rhinovirus
Epstein-Barr virus
Coccidiodes immitis
Histoplasma
capsulatum
Shigella dysenteriae
Salmonella typhi
Vibrio cholera
Hepatitis A virus
Poliovirus
Trichinella spiralis
Clostridium tetani

Pneumonia

Rickettsia rickettsi
Rabies virus
Trichophyton rubrum

Genital Tract

Plasmodium vivax
Neisseria
gonorrhoeae
Treponema pallidum
Chlamydia
trachomatis
Human papilloma
virus
Candida albicans

Meningitis
Meningitis
Tuberculosis
Influenza
Common cold
Infectious mononucleosis
Coccidiodomycosis
Histoplasmosis
Dysentery
Typhoid fever
Cholera
Infectious hepatitis
Poliomyelitis
Trichinosis
Tetanus
Rocky Mountain Spotted
Fever
Rabies
Tinea pedis (athletes
foot)
Malaria
Gonorrhea
Syphilis
Urethritis
Genital warts
Vaginitis

TRANSMISSION OF IMPORTANT WATERBORNE DISEASES

Portal of Entry
Respiratory Tract
Inhalation of water
aerosol
Skin
Penetration through
skin
Nose
Penetration through
cribriform plate
Gastrointestinal
Tract
1. Ingestion of
drinking water

2. Ingestion of water
while swimming

Pathogen

Disease

Legionella
pneumophila

Pneumonia (Legionnaires
disease)

Pseudomonas
aeruginosa
Schistosoma mansoni

Hot-tub folliculitis

Naegleria fowleri

Meningoencephalitis

Schistosomiasis

Salmonella species

Diarrhea

Shigella species

Diarrhea

Campylobacter jejuni

Diarrhea

Norovirus (Norwalklike viruses)

Giardia lambllia
Cryptosporidium
parvum
Leptospira
interrogans

Diarrhea
Diarrhea
Diarrhea
Leptospirosis

DIARRHEAL DISEASES TRANSMITTED BY FOOD

Bacterium

Typical Food

Main

Disease
Reserv
oir

Diarrheal Diseases
Gram-positive cocci
Staphylococcus aureus

Gram-positive rods
Bacillus cereus
Clostridium
perfringens
Listeria
monocytogenes
Gram-negative rods
Eschericia coli
E. coli O157:H7 strain

Custard-filled
pastries, potato,
egg, tuna fish
salad

Humans

Food poisoning, esp.

vomiting

Reheated rice
Cooked meat, stew
and gravy
Unpasteurized milk
products

Soil
Soil, animals
or humans
Soil, animals
or plants

Diarrhea
Diarrhea

Various foods and

water
Undercooked meat

Salmonella enteritidis
Salmonella typhi
Shigella species
Vibrio cholera
Vibrio parahaemolyticus
Campylobacter jejuni
Yersinia enterocolitica

Diarrhea

Humans
Cattle

Diarrhea
Hemorrhagic colitis

Domestic
animals
(esp.
poulty)
Humans
Humans
Humans
Warm salt
water
Domestic
animal
s
Domestic
animal
s

Diarrhea

Improperly canned
vegetables and
smoked fish
Unpasteurized milk
products

Soil

Botulism

Cows

Sepsis in neonate or mother

Seafood
Meat and milk
Meat

Warm salt
water
Domestic
animal
s
Rabbits
Cows

Sepsis
Brucellosis
Tularemia

Poultry, meats and

eggs
Various foods
Various foods and
water
Various foods and
water
Seafood
Various foods
Various foods

Typhoid Fever
Diarrhea
Diarrhea (dysentery)
Diarrhea
Diarrhea
Diarrhea

Nondiarrheal Diseases
Gram-positive rods
Clostridium botulinum

Listeria monocytogenes
Gram-negative rods
Vibrio vulnificus
Brucella species
Francisella tularensis

Mycobacteria
Mycobacterium bovis

Milk

Intestinal tuberculosis

BACTERIAL DISEASES TRANSMITTED BY INSECTS

Bacterium
Gram-negative rods
Yersinia pestis
Francisella
tularensis
Spirochetes
Borrelia burgdorferi
Borrelia recurrentis
Rickettsias
Rickettsia rickettsia
Rickettsia
prowazekii

Insect
Rat fleas
Ticks (Dermacentor)

Reservoir
Rodents (rats, prairie
dogs)

Disease
Plague
Tularemia

Many animals
(rabbits)
Ticks (Ixodes)
Humans

Mice
Humans

Ticks (Dermacentor)
Lice
Ticks (Dermacentor,

Dogs, rodents, ticks

Lyme disease
Relapsing fever

PROPERTY
Ehrlichia
Source
chaffeensis
Secreted from
cell
Chemistry
Location of
genes
Toxicity
Clinical effects
Mode of action
Antigenicity
Vaccines
Heat stability

Typical
diseases

EXOTOXIN
Ixodes)
Certain species of G(+) &
Gram (-) bacteria
Yes

ENDOTOXIN

Polypeptide
Plasmid or bacteriophage

Lipopolysaccharide
Bacterial chromosome

High
Various

Low
Fever, shock

Various
Induces high-titer antibodies
(antitoxins)
Toxoids used as vaccines

Includes TNF, IL-1

Poorly antigenic

Destroyed rapidly at 60oC

(except staphylococcal
enterotoxin)
Tetanus, botulism, diphtheria

Stable at 100oC for 1 hour

Cell wall of G(-) bacteria

No

No toxoids formed and no

vaccines available

Meningococcemia, sepsis

ADHERENC
E TO CELL
SURFACES
PILI (Neisseria
gonorrhoeae,
Escherichia coli)
CAPSULES
GLYCOCALYCES
(Staphylococcus
epidermidis,
viridans
streptococci)
Various
molecules that
mediate

adherence to cell surfaces are called ADHESINS

INVASION, INFLAMMATION & INTRACELLULAR SURVIVAL
ENZYMES
1. COLLAGENASE degrade collagen
2. HYALURONIDASE degrade hyaluronic acid
3. COAGULASE accelerates the formation of fibrin clot from fibrinogen; clot
protects the bacteria from phagocytosis by walling off the infected area
and coating the microorganism
4. IMMUNOGLOBULIN A (IgA) PROTEASE degrades IgA
5. LEUKOCIDINS destroy neutrophilic leukocytes and macrophages
VIRULENCE FACTORS
1. CAPSULE Streptococcus pneumoniae, Neisseria meningitidis

6. CELL WALL PROTEINS OF GRAM (+) COCCI M protein (group A

streptococci Streptococcus pyogenes, Protein A of Staphylococcus aureus)
INTRACELLULAR SURVIVAL
Mycobacterium, Legionella, Brucella, Listeria, Histoplasma
1. inhibition of the fusion of phagosome with the lysosome (avoid degradative
enzymes in the lysosome)
2. inhibition of acidification of the phagosome (reduces activity of lysosomal
degradative enzymes )
3. escape from phagosome into the cytoplasm (no degradative enzymes )
Bacteria cause disease by: INFLAMMATION and TOXIN PRODUCTION
TOXIN PRODUCTION
MAIN FEATURES OF EXOTOXINS AND ENDOTOXINS

EXOTOXINS have A-B subunit

A (active)- possesses the toxic activity
B (binding)- responsible for binding the exotoxin to specific receptors on the
membrane of the human cell)
A-subunit: act by ADP-ribosylation (A-subunit is an enzyme that catalyzes the
addition of adenosine diphosphate ribose- ADP-ribose- to the target protein in the
human cell INACTIVATES or HYPERACTIVATE THE CELL SYMPTOMS
EXOTOXINS are released from bacterial by SECRETION SYSTEMS
INJECTOSOME/TYPE III SECRETION SYSTEM molecular syringe (needlelike projection) & transport pumps in the bacterial cell membrane

EFFECTS OF ENDOTOXINS
CLINICAL FINDINGS

MEDIATOR/MECHANISM

FEVER

IL-1, IL-6

HYPOTENSION
(SHOCK)
INFLAMMATION

TNF, NITRIC OXIDE, BRADYKININ

COAGULATION (DIC)

C5a produced by the alternative pathway of complement

attracts neutrophils
Activation of tissue factor

IMPORTANT MECHANISMS OF ACTION OF BACTERIAL EXOTOXINS

IMPORTANT BACTERIAL EXOTOXINS
MECHANISM OF
ACTION
ADP- ribosylation

EXOTOXIN
Diphtheria toxin, cholera toxin, Escherichia coli
heat-labile toxin, pertussis toxin

Superantigen

TSST, staphylococcal enterotoxin, erythrogenic

toxin
BACTERIUM
MECHANISM
OF
ACTION
Protease
Tetanus toxin,
botulinum
toxin,
lethal factor of
Corynebacterium anthrax toxin,
Inactivates
EF-2
by
ADP-ribosylation (inhibits protein
scalded skin toxin
diphtheria
synthesis)
Lecithinase
Clostridium
perfringens alpha toxin
Clostridium tetani
Blocks the release of the inhibitory NT GLYCINE by
proteolytic cleavage of releasing proteins
Clostridium botulinum
Clostridium difficile

Blocks release of ACETYLCHOLINE by proteolytic

cleavage of releasing proteins
Exotoxins A and B inactivate GTPases by glycosylation

Clostridium perfringens

Alpha toxin is a lecithinase; enterotoxin is a superantigen

Bacillus anthracis

Edema factor is an adenylate cyclase; lethal factor is a

protease that cleaves MAP kinase (required for cell
division)