Transcript Microbes and Human Disease

Microbes and Human Disease
The seven (7) components of
pathogenicity:
What it takes to cause disease
1) Maintain a reservoir
• All pathogens must have at least 1 reservoir
• Most common for humans:
– Other humans
– Animals
– Environment
Human reservoirs
• Carry MO’s too fragile to
live in the environment
– Pertussis, measles, gonorrhea
• Healthy people
– Incubatory carrier
• Staph
• Chlamydia
• HIV
– Chronic carrier
• Typhoid fever
• Strep
• Peptic ulcers?
• Sick people
Animal reservoirs
• Typically within warm-blooded
animals
• Disease transmitted from animal
to man = zoonosis (>150
known)
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Lyme disease
Rabies
Leptospirosis
RMSP
Anthrax
Typhus
West Nile encephalitis
Environmental reservoir
• Mo’s tough/robust
enough to survive
environmental variation
– From water:
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Vibrio
Salmonella
Shigella
Escherichia
– From soils:
• Clostridium
2) Enter a suitable host
• Transmission is via a “portal of entry”
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Nose/upper respiratory
Skin
Conjunctiva
Mouth – g.i.
Urethra
• Mucus membrane (400 m2 – area of basketball court)
– Placenta
Mode of transmission
a)
b)
c)
Respiratory droplets
Fomites
Direct contact
i.
ii.
d)
Fecal-oral route
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ii.
e)
direct contact
indirect contact
Arthropod vector
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ii.
f)
g)
touching/kissing
congenital
biological vector
mechanical vector
Airborne transmission
Parenteral transmission
3) Adhere to the surface of a host
• If no adhesion, there is no problem…
• Bacterial adhesins – glycoprotein
glycolipid
-Streptococcus pneumoniae
-Bordetella pertussis
-Haemophilus influenza
• Bacterial pili – Escherichia and Neisseria
• Receptors on our cells are typically sugars
Adhesins or ligands
Figure 15.1 - Overview
• Specificity exists
between pathogen and
host
• Some adhesins
stimulate host cell
phagocytosis and are
called invasins
Biofilms
• Affects blood vessels,
teeth, catheters, and
water pipes
• Strep mutans degrades
glucose  dextrans
which it uses for
capsule
• Bacterial biofilm in
b.v.’s stimulate
inflammation at site 
lipid deposition
4) Ability to invade host cells
• Invasion allows bacteria to enter safe and
nutrient rich environment
• Most penetrate via phagocytosis
• Many kill/destroy host cell
• Other effects:
– Surface damage/direct damage
– Toxin production transported by blood/lymph
to other locations
– Induce hypersensitivity/allergic reaction
Exotoxins: Type 1
• Called “superantigens”
• Stimulate  levels of
cytokines to be
released from T cells
into bloodstream
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Ex: staph food poison, staph TSST-1
Nausea
Diarrhea
Loss of blood volume
Shock  death
Exotoxins: Type II
• Extracellular enzymes
1) Act to lyse cells
– Referred to as:
• Hemolysins
• Leukocidins
• Assayed via blood agars
– α-hemolysis
– β-hemolysis
– γ-hemolysis
2) Also:
coagulases
kinases
hyaluronidase
Exotoxins: Type III
• Typical exotoxin-highly
potent!
• a domain = active
• b domain = binding
• a unit disrupts ATP
formation or disrupts
protein synthesis
Figure 15.5 - Overview
Type III Exotoxins (cont’d)
• Named several ways:
– By microbe:
• Botulinum toxin
• Vibrio enterotoxin
– By disease:
• Diptheria toxin
• Tetanus toxin
– Target tissue
• Cytotoxin
– Cardiotoxin
– Hepatotoxin
• Neurotoxin
• Enterotoxin
Antitoxins
• As with any protein,
animals can produce
antibodies against an
exotoxin = antitoxin
• “toxoids” can be
produced to trigger
antitoxin production
Endotoxins
• Requires bacterial cell
death and release of LPS
• Lipid A of LPS
• All produce similar
symptoms:
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Figure 15.6 - Overview
Fever
Weakness
Generalized aches
Shock  death
Table 15.3 (1 of 2)
Table 15.3 (2 of 2)
5) Evasion of Host defenses
• Upon entering the body foreign cells are
assaulted by cells and proteins of IR
• Bacteria have evolved several ways to block
host IR through:
1) preventing phagocytosis
2) buying time
Prevention of phagocytosis
• Primary means of
particle removal from
the body
• Capsules – insulate
surface antigens
M proteins project as pili for
strong attachment and to
prevent complement from
attaching
• M proteins
“buying time”
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Antigenic variation
IgA protease
Serum resistance
Waxes in cell wall
Sequestering Fe
6) Multiplying in the host
• Produces the disease state
– Involves components 4 and 5
• Ability to cause disease relates to:
– Toxin production
– Effects of prolonged IR to the body in chronic
infections
7) Leaving the Host
• Respiratory droplets
• gi pathogens – fecaloral route
• gu tract – across
mucus memb of
urethra
• Parenteral route – via
blood