Download Microbial Mechanisms of Pathogenicity (Chapter 15) Lecture

Microbial Mechanisms of Pathogenicity
(Chapter 15)
Pathogenicity = ability to cause disease
Virulence = degree of pathogenicity
-pathogens must first gain access to the host:
-must adhere and penetrate before infection
is established
-then must continually evade host defenses
-infection usually causes host damage: disease
Lecture Materials
for
Amy Warenda Czura, Ph.D.
Suffolk County Community College
To cause disease a pathogen must:
1. gain access to the host
2. adhere to host tissues
3. penetrate or evade host defenses
4. damage the host, either:
- directly
- accumulation of microbial wastes
Eastern Campus
Primary Source for figures and content:
Tortora, G.J. Microbiology An Introduction 8th, 9th, 10th ed. San Francisco: Pearson
Benjamin Cummings, 2004, 2007, 2010.
Entry Into Host
1. Portals of Entry
A. Mucous membranes (moist mucosa)
-most common route for most pathogens
-entry through mucus membranes:
1. respiratory tract
(most common)
2. gastrointestinal tract
3. urinary/genital tracts
4. conjunctiva
B. Skin (keratinized cutaneous membrane)
-some pathogens infect hair follicles and
sweat glands
-few can colonize surface
-unless broken, skin is usually an
impermeable barrier to microbes
Amy Warenda Czura, Ph.D.
C. Parenteral route
-penetrate skin: punctures, injections,
bites, cuts, surgery, etc.
-deposit organisms directly into deeper
tissues
-most microbes must enter through their
preferred portal of entry in order to cause
disease
-some can cause disease from many routes of
entry
-most usually also exit the host from the same
original portal to spread disease
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SCCC BIO244 Chapter 15 Lecture Notes
2. Numbers of Invading Microbes
-likelihood of disease increases as the
number of invading pathogens increases
ID50 (Infectious Dose) = number of
microbes required to produce infection in
50% of the population
-different ID50 for different pathogens
-different ID50 for different portals of
entry for the same pathogen
LD50 (Lethal Dose) amount of toxin or
pathogen necessary to kill 50% of the
population in a particular time frame
-pathogen has surface
molecules called
adhesions or ligands
that bind specifically
to the host surface
receptors
-most microbial adhesions are glycoproteins
or lipoproteins located on the glycocalyx,
capsule, capsid, pili, fimbriae or flagella
-most host receptors are typically proteins
(for virus) or carbohydrates (for bacteria)
in the wall or membrane of host cell
Biofilms:
-formed when microbes adhere to a surface
that is usually moist and contains organic
matter
-each microbe secretes
glycocalyx
allowing other
microbes to adhere;
a large mass is formed
3. Adherence
= attachment to the host by the microbe at
portal of entry
-usually necessary for virulence
-blocking adhesion can prevent disease
-the biofilm is
resistant to
disinfectants
and antibiotics
(outer layer
protects inner
layers)
-problem for catheters and surgical implants:
serves as chronic reservoir
2. Cell Wall Components
A. M protein of Streptococcus pyogenes:
-heat and acid resistant
-mediates attachment of bacterium to
epithelial cells
-resists phagocytosis by leukocytes
http://www.primary-plus.com/wp-content/uploads/2009/12/biofilm.jpg
Penetration of Host Defenses
1. Capsules
= organized glycocalyx layer
(carbohydrates) outside cell wall
-impairs phagocytosis: prevents engulfment
and destruction
by leukocytes
-if present, is
usually required
for virulence
-some nonantigenic
Amy Warenda Czura, Ph.D.
http://www.nibib.nih.gov/nibib/image/Eadvances/June07/EHEgelman_neisseria_pili.jpg
B. Fimbriae + Opa (membrane protein) used
by Neisseria gohorrhoeae:
-promote attachment and uptake by host
epithelial cells and leukocytes
-Neisseria then grows inside these cells
C. Mycolic acid (waxy) of Mycobacterium
tuberculosis
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SCCC BIO244 Chapter 15 Lecture Notes
-resist digestion by
phagocytes
-Mycobacterium then
grows inside phagocyte
D. Collagenase: breaks down collagen
(fibrous part of connective tissue) for
invasion into muscles and organs
e.g. Clostridium species
E. IgA proteases: destroy host IgA
antibodies found in mucous secretions
to allow adherence and passage at
mucus membranes
e.g. Neisseria species that infect CNS
4. Antigenic Variation
-pathogen alters its surface antigens to escape
attack by antibodies and immune cells
e.g. Neisseria gonorrhoeae
-has many versions of the Opa gene
-can alter which one is being expressed
e.g. influenza virus
-constant genetic
recombination
between flu
viruses: always
new spike proteins
http://upload.wikimedia.org/wikipedia/commons/d
/d3/Mycobacterium_avium-intracellulare_01.png
3. Enzymes (exoenzymes)
A. Coagulases: clot fibrin in blood to create
protective barrier against host defenses
B. Kinases: dissolve clots (fibrinolysis) to
allow escape from isolated wounds e.g.
Streptokinase (Streptococcus pyogenes)
Staphylokinase (Staphylococcus aureus)
C. Hyaluronidase: hydrolyzes hyaluronic
acid (‘glue’ that holds together connective
tissues and epithelium barriers) allowing
deeper invasion
e.g. Clostridium
species: allows
them to cause
gangrene
(tissue necrosis)
http://www.humanillnesses.com/images/hdc_0001_0001_0_img0044.jpg
5. Penetration into Host Cytoskeleton
-use actin of host cell to penetrate and move
within the cell
A. Invasins: surface proteins produced by
bacteria to control actin
e.g. Salmonella
-rearrange actin:
cause the cell
membrane to
wrap around the
microbe and take it
into the cell (endocytosis)
-allows Salmonella to penetrate intestinal
epithelium
e.g. Shigella and
Listeria
-trigger
endocytosis
-polymerize
actin behind
bacterium to propel through host cell
Amy Warenda Czura, Ph.D.
B. Cadherin: allows penetration between
cells at intercellular junctions
e.g. Shigella and Listeria: move
between cells at cell junctions.
Damage to Host Cells
1. Using Hosts Nutrients
e.g. iron
-required for all cells (electron transport
chain: cytochromes) both host and
pathogen
-host usually does not have free iron
available (free iron leads to easy
colonization by pathogens)
-humans bind unused iron to transport
proteins: transferrin
-pathogens can produce siderophores:
secreted by bacteria to compete iron from
host proteins, siderophore iron complex
then absorbed by bacteria
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SCCC BIO244 Chapter 15 Lecture Notes
2. Direct Damage To Colonized Area
-growth and replication in host cells: results
in host cell lysis
-penetration through host cells (mucosa,
organs) causes damage
-lysis of host cells to obtain nutrients
3. Production of Toxins
Toxins = poisonous substance produced by
microbes
-tend to cause widespread damage/disease
in host
-may be necessary for virulence
A. Exotoxins
-produced inside the bacteria and either
secreted or released following microbe
lysis
-toxin genes are often found on plasmids or
via lysogenic phages
-most are enzymes
-function to destroy certain host cell parts
or inhibit particular metabolic functions
-damage from toxin results in the particular
signs or symptoms of a disease
-can be named for the disease, type of cell
attacked or organism that produces it
e.g. tetanus toxin: causes tetanus
(contraction) of muscle
-three types of exotoxins:
1) A-B toxins
Two parts:
A is the
enzyme
that
disrupts
some
cell
activity
B binds
surface
receptors
to bring A
into the
host cell
e.g. botulinum & tetanus toxin
e.g. leukocidins: make protein channels
in phagocytic leukocytes
e.g. hemolysins: make protein channels in
RBCs
(!-hemolysis: Steptococcus pyogenes)
3) Superantigens
-bacterial proteins that cause
proliferation of T cells and release of
cytokines
-excessive cytokines can cause fever,
nausea, vomiting, diarrhea, shock and
death (septic shock)
e.g. toxic shock syndrome
(Staphylococcus)
e.g. enterotoxins: Staphylococcal food
poisoning
B. Endotoxins
-part of the outer membrane portion of
the cell wall of gram negative bacteria:
Lipopolysaccharide (LPS)
2) Membrane disrupting toxins
-cause lysis of the host cell by
disrupting the plasma membrane
Amy Warenda Czura, Ph.D.
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SCCC BIO244 Chapter 15 Lecture Notes
-released when dead cells lyse
-in blood, causes macrophages to release
high levels of cytokines resulting in chills,
fever, weakness, aches, small blood clots,
tissue necrosis, shock and death
e.g. endotoxic shock: critical loss of blood
pressure due to bacterial endotoxins (LPS)
Sterile solutions can contain LPS: bacteria
dies in sterilization but LPS is unaltered
Due to serious consequences at very low
levels of LPS, it is essential to test medical
devices and solutions for endotoxin
-Limulus Amoebocyte Lysate Assay:
-horseshoe crab blood
-contains amoebocytes that will lyse and
clot in the presence of extremely low
levels of LPS (only way to confirm IV
solutions are “endotoxin free”)
http://www.globalclassroom.org/spawn1.jpg
http://3r-training.tierversuch.ch/files/mediapics/Fendrich_Pyrogen/full/Fennrich%20Bild07%20E.gif
Plasmids, Lysogeny and Pathogenicity
-plasmids carry genes for resistance to
antibiotics and/or virulence factors (e.g.
exotoxins, fimbriae) between bacteria
allowing new bacteria to become
pathogenic
e.g. hemorrhagic E. coli
(fimbrae + shiga toxin)
-prophages can result in lysogenic
conversion that results in pathogenic ability
of the bacteria carrying them (new
production of endotoxin)
e.g. Diptheria toxin (Cornebacterium)
Cholera toxin (Vibrio)
-phage can be transmitted to nonpathogenic
strains making them virulent
Amy Warenda Czura, Ph.D.
http://www.udel.edu/PR/UDaily/2004/hcrab404lg.jpg
Pathogenic Properties of Virus
1. Mechanisms to evade host defenses
A. Grow inside host cells to hide from
immune defense
B. Kill immune cells
e.g. HIV – TH Cells
2. Cytopathic effects
= visible effects of viral infection on
host cell: some effects will kill the cell,
some will just change the cell
A. stop DNA, RNA and/or protein synthesis
e.g. Herpes virus block mitosis
B. lysosomal autolysis of host cells
e.g. Influenza: bronchiolar epithelium
C. production of inclusion bodies (visible
viral parts inside the cell)
can identify
a particular virus
e.g. Rabies
virus:
Negri bodies
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SCCC BIO244 Chapter 15 Lecture Notes
D. syncytium formation (neighboring cells
fuse together)
e.g. Varicella
Zoster virus
Eukaryotic Pathogens
1. Fungi:
-produce toxins causing allergies or disease
e.g. -chronic sinusitis (black molds)
-Stachybotrys: headaches, vomiting,
mental disturbance
E. change in cell function
e.g. Measles
F. production of interferons by host cell
(triggers host immune response)
G. induce antigenic changes on host cell
surface (triggers destruction of infected
cell by host immune response)
H. induce chromosomal changes
I. cell transformation: may activate or
deliver oncogenes resulting in loss of
contact inhibition (cancer)
e.g. Papilloma virus
-invasive systemic mycosis in immune
compromised patients
e.g. Candida
-mushrooms: mycotoxins
may be hallucinogenic
or deadly
2. Protozoa:
-can grow inside host cells causing lysis
e.g. Malaria (Plasmodium)
-use host cells
as food source
-produce wastes
that cause disease
3. Algae
-produce neurotoxic substances
e.g. shellfish
poisoning
(dinoflagellates)
http://wiz2.pharm.wayne.edu/module/plasmodium.jpg
Amy Warenda Czura, Ph.D.
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SCCC BIO244 Chapter 15 Lecture Notes