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Microbial Mechanisms of
Pathogenicity
Basic Medical Microbiology, 2016
Pathogenic mechanisms of microorganisms
pathogenicity
virulence factors
toxigenesis
normal micro biota
Resident flora
The resident flora are a huge and rich mixed population
of microorganisms residing on body surfaces exposed
to the environment including the skin, mucous
membranes, parts of the gastrointestinal tract, urinary
tract, reproductive tract, and upper respiratory tract, and
are important to the host.
Respiratory System
 Staphylococcus,
Corynebacterium,
Haemophilus
influenzae, Strep. Pneumoniae, Step. Viridans
Skin
 Staphylococcus, Corynebacterium, Propionibacterium
genera, fungi (genus
Factors affecting the Course of
Infection and Disease
1.
2.
3.
Pathogenicity and Virulence
Mechanism of Infection and Disease
Virulence factors
Pathogenicity and Virulence
• Pathogenicity is a property/ability of microorganisms to cause
infection and disease
• Virulence is the precise factors used by the microbe to invade, and
damage host tissues (helps define the degree of pathogenicity)
• Pathogenicity varies with a microbe’s ability to invade or harm
host tissues, and with the condition of host defenses
• A true /primary pathogen produces virulence factors that allow
it to readily evade host defenses and to harm host tissues. True
pathogens can infect normal, healthy hosts with intact defenses
• An opportunistic pathogen is not highly virulent but can cause
disease in persons whose defenses are compromised by
predisposing conditions such as age, genetic defects, medical
procedures, and underlying organic disease.
Mechanism of Infection and
Disease
• The portal of entry is the route by which microbes
enter the tissues; primarily via skin, alimentary tract,
respiratory tract (pneumonia, tuberculosis), urinogenital
tract (sexually transmitted diseases), or placenta.
• Pathogens that come from outside the body are
exogenous; those that originate from normal flora are
endogenous
• The size of the infectious dose is of great importance in
pathogenesis
• In the process of adhesion, a microbe attaches to the
host cell by means of fimbriae, flagella, capsules or
receptors that position it for invasion
Virulence Factors
• Exoenzymes digest epithelial tissues, disrupt
tissues, and permit invasion of pathogens
• Toxigenicity is a microbe’s capacity to produce
toxins at site of multiplication which affect cellular
targets.
• Antiphagocytic factors include Leukocidins (white
blood cell poisons) and capsules
Steps for infections by pathogenic
bacteria include;
1.
2.
3.
4.
5.
6.
7.
Maintain a reservoir
Initially be transported to the host.
Adhere to, and/ or colonize the host
Multiply (grow) or complete its life cycle on
or in the host or the host’s cells.
Initially evade the host defense mechanisms
Possess the ability to damage the host.
Leave the host and return to the reservoir or
enter a new host (portal of exit).
Pathogenicity - ability to cause disease
Virulence - degree of pathogenicity

Many properties that determine a microbe’s
pathogenicity or virulence are unclear or
unknown

But, when a microbe overpowers the hosts
defenses, disease results!
10
Defense Mechanisms of the Host

To protect the body against pathogens, the
immune system relies on a multilevel network of
physical barriers, immunologically active cells,
and a variety of chemicals.
• first line of defense – any barrier that blocks invasion
at the portal of entry – nonspecific
• second line of defense – protective cells and fluids;
inflammation and phagocytosis – nonspecific
• third line of defense – acquired with exposure to
foreign substance; produces protective antibodies and
creates memory cells – specific
11
Physical or Anatomical Barriers:
First Line of Defense
Skin and mucous membranes of respiratory, urogenital,
eyes and digestive tracts
• outermost layer of skin is composed of epithelial cells
compacted, cemented together and impregnated with
keratin; few pathogens can penetrate if intact
• flushing effect of sweat glands
• damaged cells are rapidly replaced
• mucous coat impedes attachment and entry of bacteria
• blinking and tear production
• stomach acid
• nasal hair traps larger particles
12
Nonspecific Chemical Defenses

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Sebaceous secretions
Lysozyme, an enzyme that hydrolyzes the cell wall of
bacteria, in tears
High lactic acid and electrolyte concentration in sweat
Skin’s acidic pH
Hydrochloric acid in stomach
Digestive juices and bile of intestines
Semen contains antimicrobial chemical.
Vagina has acidic pH.
13
14
Genetic Defenses



Some hosts are genetically immune to the
diseases of other hosts.
Some pathogens have great specificity.
Some genetic differences exist in
susceptibility.
15
Portals of Entry

1. Mucus Membranes

2. Skin

3. Parentarel
1. Mucus Membranes

A. Respiratory Tract
• microbes inhaled into
mouth or nose in
droplets of moisture or
dust particles
• Easiest and most
frequently traveled
portal of entry
Common Diseases contracted via
the Respiratory Tract

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
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


Common cold
Flu
Tuberculosis
Whooping cough
Pneumonia
Measles
Strep Throat
Diphtheria
Mucus Membranes

B. Gastrointestinal Tract
• microbes gain entrance thru
contaminated food & water
or fingers & hands
• most microbes that enter the
G.I. Tract are destroyed by
HCL & enzymes of stomach
or bile & enzymes of small
intestine
Common diseases contracted via
the G.I. Tract
 Salmonellosis
• Salmonella sp.

Shigellosis
• Shigella sp.

Cholera
• Vibrio cholorea

Ulcers
• Helicobacter pylori

Botulism
• Clostridium botulinum
Fecal - Oral Diseases

These pathogens enter the G.I. Tract at one
end and exit at the other end.

Spread by contaminated hands & fingers or
contaminated food & water

Poor personal hygiene.
Mucus Membranes of the Genitourinary System - STD’s
Gonorrhea
Neisseria gonorrhoeae
Syphilis
Treponema pallidum
Chlamydia
Chlamydia trachomatis
HIV
Herpes Simplex II
Mucus Membranes

D. Conjunctiva –
•

mucus membranes that cover
the eyeball and lines the eyelid
Trachoma
• Chlamydia trachomatis
2nd Portal of Entry: Skin

Skin - the largest organ of the body. When
unbroken is an effective barrier for most
microorganisms.

Some microbes can gain entrance thru
openings in the skin: hair follicles and sweat
glands
3rd Portal of Entry: Parentarel

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
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Microorganisms are deposited into the
tissues below the skin or mucus membranes
Punctures
injections
bites
scratches
surgery
splitting of skin due to swelling or dryness
Preferred Portal of Entry


Just because a pathogen enters your body it
does not mean it’s going to cause disease.
pathogens - preferred portal of entry
Preferred Portal of Entry

Streptococcus pneumoniae
• if inhaled can cause pneumonia
• if enters the G.I. Tract, no disease

Salmonella typhi
• if enters the G.I. Tract can cause Typhoid Fever
• if on skin, no disease
Number of Invading Microbes


LD50 - Lethal Dose of a microbes toxin that
will kill 50% of experimentally inoculated
test animal
ID50 - infectious dose required to cause
disease in 50% of inoculated test animals
• Example: ID50 for Vibrio cholerea 108 cells
(100,000,000 cells)
• ID50 for Inhalation Anthrax - 5,000 to 10,000
spores ????
How do Bacterial Pathogens
penetrate Host Defenses?
1. Adherence - almost all
pathogens have a means to
attach to host tissue
Binding Sites
adhesins
ligands
Adhesins and ligands are usually
on Fimbriae

Neisseria gonorrhoeae
 ETEC
(Entertoxigenic E. coli)

Bordetello pertussis
2. Capsules

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K. pneumoniae

Prevent phagocytosis
attachment
Streptococcus
pneumoniae
Klebsiella pneumoniae
Haemophilus
influenzae
Bacillus anthracis
Streptococcus mutans
Yersinia pestis
3. Enzymes

Many pathogens secrete enzymes that
contribute to their pathogenicity
A. Leukocidins

Attack certain types of WBC’s

1. Kills WBC’s which prevents phagocytosis
2. Releases & ruptures lysosomes

• lysosomes - contain powerful hydrolytic
enzymes which then cause more tissue damage
B. Hemolysins - cause the lysis of RBC’s
Streptococci
1. Alpha Hemolytic Streptococci
- secrete hemolysins that cause the
incomplete lysis or RBC’s
2. Beta Hemolytic Streptococci
- secrete hemolysins that cause the complete lysis
of RBC’s
3. Gamma Hemolytic Streptococci - do
not secrete any hemolysins
C. Coagulase - cause blood to
coagulate

Blood clots protect bacteria from
phagocytosis from WBC’s and other host
defenses

Staphylococci - are often coagulase positive
• boils
• abscesses
D. Kinases - enzymes that dissolve
blood clots


1. Streptokinase - Streptococci
2. Staphylokinase - Staphylococci

Helps to spread bacteria - Bacteremia

Streptokinase - used to dissolve blood clots in the
Heart (Heart Attacks due to obstructed coronary blood
vessels)
E. Hyaluronidase

Breaks down Hyaluronic acid (found in
connective tissues)

“Spreading Factor”

mixed with a drug to help spread the drug
thru a body tissue
F. Collagenase

Breaks down collagen (found in many connective
tissues)

Clostridium perfringens - Gas Gangrene
• uses this to spread thru muscle tissue
G. Necrotizing Factor
- causes death (necrosis) to tissue cells
“Flesh Eating Bacteria”
Necrotizing fasciitis
Summary of How Bacterial
Pathogens Penetrate Host Defenses



1. Adherence
2. Capsule
3. Enzymes
•
•
•
•
•
•
•
A. leukocidins
B. Hemolysins
C. Coagulase
D. Kinases
E. Hyaluronidase
F. Collagenase
G. Necrotizing Factor
4. Toxins


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Poisonous substances produced by
microorganisms
toxins - primary factor - pathogenicity
220 known bacterial toxins
• 40% cause disease by damaging the Eukaryotic
cell membrane

Toxemia
• Toxins in the bloodstream
Diseases caused by exotoxins
Disease
Bacterium
Botulinism
Clostridium botulinum
Tetanus
Clostridium tetani
Gas gangrene & food poisoning
Clostridium perfringens & other species of clostridium
Diphtheria
Corynebacterium diphtheriae
Scalded skin syndrome, food Staphylococcus aureus
poisoning, and toxic shock
syndrome
Cholera
Vibrio cholera
Scarlet fever
Streptococcus pyogenes
Traveler’s diarrhea
Enterotoxigenic E. coli & Shigella spp
2 Types of Toxins

1. Exotoxins
• secreted outside the bacterial cell

2. Endotoxins
• part of the outer cell wall of Gram (-) bacteria
Exotoxins

Mostly seen in Gram (+) Bacteria

Most gene that code for exotoxins are
located on plasmids or phages
3 Types of Exotoxins

1. Cytotoxins
• kill cells

2. Neurotoxins
• interfere with normal nerve impulses

3. Enterotoxins
• effect cells lining the G.I. Tract
Response to Toxins

If exposed to exotoxins: antibodies against the
toxin (antitoxins)
 Exotoxins inactivated ( heat, formalin or phenol)
no longer cause disease, but stimulate the
production of antitoxin
• altered exotoxins - Toxoids

Toxoids - injected to stimulate the production of
antitoxins and provide immunity
Example: DPT Vaccine

D - Diphtheria
• Corynebacterium diphtheriae

P - Pertussis
• Bordetello pertussis

T - Tetanus
• Clostridium tetani
DPT - Diphtheria Toxoid
Pertussis Antigen
Tetanus Toxoid
Required Immunizations
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1. Diphtheria
2. Pertussis
3. Tetanus
4. Measles
5. Mumps
6. Rubella
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Corynebacterium diphtheriae
Bordetello pertussis
Clostridium tetani
Measles virus
Mumps virus
Rubella virus
• German Measles

7. Polio
 8. Hib
 9. Hepatitis B
 10.Chicken Pox

Polio virus
 Haemophilus influenzae
 Hepatitis B Virus
 Varicella-zoster virus
Type of Vaccines

D
 P
 T
 M
 M
 R
 Polio
• Salk
• Sabin
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Hib
HBV
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Toxoid
Antigen
Toxoid
Attenuated
Attenuated
Attenuated
IPV – Inactivated Polio virus (Killed) 1953
OPV – Oral Polio vaccine (attenuated) 1964
Conjugated vaccine
Recombinant vaccine (antigen) yeast
• Capsid produced by genetically
engineered yeast

Chicken Pox  Attenuated
Most genes that code for exotoxins - plasmids
or phages

Lysogenic convergence
 Diphtheria
 Cytotoxin inhibits
protein synthesis resulting in cell death
 Pseudomembrane
• fibrin, dead tissue,
bacterial cells
Lysogenic Convergence


Scarlet Fever
Streptococcus pyogenes
• lysogenic convergence

prophage
• cytotoxin - damages blood capillaries and results in a skin rash
• Strep Thoat with a rash
Diseases caused by Neurotoxins

Botulism
• Clostridium botulinum
• Gram (+), anaerobic, spore-forming rod, found in
soil
• works at the neuromuscular junction
• prevents impulse from nerve cell to muscle cell
• results in muscle paralysis
Tetanus (Lock Jaw)


Clostridium tetani
Gram (+), spore-forming, anaerobic rod
 neurotoxin acts on nerves, resulting in the
inhibition of muscle relaxation
 tetanospasmin - “spasms” or “Lock Jaw”
Diseases caused by Enterotoxins

Cholera
• Vibrio cholerae
• Gram (-) comma
shaped rods
Cholera toxin


Converts ATP into cAMP
causes cells to excrete Cl- ions and inhibits
absorption of Na+ ions
 Electrolyte imbalance
 H2O leaves by osmosis
 H2O Loss (Diarrhea)
Severe cases, 12 - 20 liters of liquid lost
in a day

Untreated cases - Mortality Rate about 50%

Mortality may be reduced to about 1%
• administering fluids and electrolytes
EHEC (Enterohemorrhagic E. coli)
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E. coli (0157:H7)
enterotoxin causes a hemolytic
inflammation of the intestines
results in bloody diarrhea
• Toxin
•
•
•
•
•
alters the 60S ribosomal subunit
inhibits Protein Synthesis
Results in cell death
lining of intestine is “shed”
Bloody Diarrhea (Dysentary)
Endotoxins - part of the Gram (-)
Bacterial cell wall

LPS (Lipopolysaccharides)
• O Antigen
• Lipid A

Lipid A - Toxin portion of the LPS
• responsible for Fever that is associated with
many Gram (-) Bacterial infections
• Gram (-) cells are “digested” endotoxins are
released - fever
• Antibiotics
Differences between exotoxins and endotoxins
Property
Exotoxins
Endotoxins
Bacterial source
Mostly from gram-positive bacteria
Almost exclusively from gram-negative bacteria
plus a few gram-positive bacteria
Relation
microbe
to Metabolic product of growing cell
Presence from LPS of outer membrane of cell wall
& released only with lysis of cell
Chemistry
Protein or short peptide
Lipid portion (lipid A) of LPS of outer membrane
Heat stability
Unstable; can easily be destroyed at 60- 80oC (except Stable, can withstand autoclaving (121oC for one
staphylococcal enterotoxins)
hour.
Toxicity
High
Immunology
Can be converted to toxoids, neutralized by Not easily neutralized by antitoxin, therefore
antitoxins
effective toxoids cant be made
Pharmacology
Specific for a particular cell structure or function in General such as fever, weakness, aches, and shock;
the host (mainly cytotoxins, neurotoxins & all produce the same effects
enterotoxins)
Lethal dose
Small
Representative
disease
Gas gangrene, tetanus, botulinism, diphtheria, scarlet Typhoid fever, urinary tract infections, and
fever, cholera, traveler’s diarrhea
meningococcal meningitis
Low
Considerably large