Transcript Microbiology

Ch 15
Microbial
Mechanisms
of
Pathogenicity
Student Learning Outcomes
Identify the principal portals of entry and exit.
Using examples, explain how microbes adhere to host cells.
Explain how capsules and cell wall components contribute to
pathogenicity.
Compare the effects of coagulases, hyaluronidase, and
collagenase.
Describe the function of siderophores.
Provide an example of direct damage, and compare this to
toxin production.
Contrast the nature and effects of exotoxins and endotoxins.
Outline the mechanisms of action of A-B toxins and
superantigens
Vocabulary
Pathogenicity: Ability of a pathogen to cause disease by
overcoming the host defenses
Virulence: ________ of pathogenicity.
Attachment via
______________
is step 1:
Bacteria use
___________
___________
Viruses use
___________
(Preferred) Portals of Entry
Mucous membranes
 Conjunctiva
 Respiratory tract: Droplet inhalation of moisture
and dust particles. Most common portal of entry.
 GI tract: food, water, contaminated fingers
 Genitourinary tract
Skin
 Impenetrable for most microorganisms; possible to
enter through hair follicles and sweat ducts.
Parenteral Route
Trauma (S. aureus, C. tetani)
Arthropods (Y. pestis)
Injections
Numbers of Invading Microbes
ID50: ____________________________________
LD50: ____________________________________
Bacillus anthracis
Portal of Entry
ID50
Skin
10–50 endospores
Inhalation
10,000–20,000 endospores
Ingestion
250,000–1,000,000 endospores
at http://www.cdc.gov/ncidod/EID/vol5no4/cieslak.htm
Clinical and Epidemiologic Principles of Anthrax
What is the LD50 for the bacterial
toxin tested in the example below?
Adherence
Adhesins: surface
projections on pathogen,
mostly made of glycoproteins
or lipoproteins.
Adhere to complementary
receptors on the host cells.
Adhesins can be part of:
 Glycocalyx: e.g.Streptococcus mutans
Fig 15.1
 Fimbriae (also pili and flagella): e.g.E. coli
Host cell receptors are most commonly sugars (e.g.
mannose for E. coli
Biofilms provide attachment and resistance to
antimicrobial agents.
Penetration of Host Defenses
 Capsules: inhibition or prevention of _____________
 Cell Wall Proteins: e.g. M protein of S. pyogenes
 Antigenic Variation:
Avoidance of IS, e.g.
Trypanosoma
Neisseria
 Penetration into the Host Cell Cytoskeleton:
Salmonella and E. coli produce invasins, proteins that
cause the actin of the host cell’s cytoskeleton to form a
basket that carries the bacteria into the cell. See Fig 15.2
MASTERING ANIMATION Virulence Factors: Hiding from Host Defenses
Penetration into the Host Cell Cytoskeleton
 Invasins
 Salmonella
alters host
actin to
enter a host
cell
 Use actin to
move from
one cell to
the next
 Listeria
Fig 15.2
Enzymes
Coagulase: Blood clot formation. Protection from
phagocytosis (virulent S. aureus)
Kinase: blood clot dissolve (e.g.: streptokinase)
Hyaluronidase: (Spreading factor) Digestion of
“intercellular cement”  tissue penetration
Collagenase: Collagen hydrolysis
IgA protease: IgA destruction
Enzymes Used for Penetration
How Pathogens Damage Host Cells
1. Direct damage
2. Use host’s nutrients; e.g.: Iron
3. Produce toxins
4. Induce hypersensitivity
reaction
Mastering: Virulence Factors – Penetrating Host Tissues &
Enteric Pathogens
Toxins
Exotoxins: proteins (Gramand + bacteria can produce)
Endotoxins: Gram- bacteria
Foundation Fig 15.4
only. LPS, Lipid A part 
released upon cell death.
Symptoms due to vigorous
inflammation. Massive
release  endotoxic shock
Mastering: Virulence Factors – Exotoxins
Vocabulary related to Toxin Production
 Toxin: Substances that contribute to
pathogenicity.
 Toxigenicity: Ability to produce a toxin.
 Toxemia:
 Toxoid:
 Antitoxin:
Exotoxins Summary
Source:
Relation to microbe:
Chemistry:
Fever?
Neutralized by
antitoxin?
LD50:
Gram + and Gram -
By-products of growing cell
_________
No
_________
Small
Circulate to site of activity. Affect body before immune
response possible.
Exotoxins with special action sites: Neuro-, and enterotoxins
Toxin Examples
Portal of Entry
Botulinum (in mice)
Staphylococcal enterotoxin
Shiga toxin
LD50
0.03 ng/kg
1.35 g/kg
250 ng/kg
Which is the least potent toxin?
A. Botulinum
B. Shiga
C. Staph
Type of Exotoxins:
A-B
Exotoxins
Fig 15.5
Fig 15.5
Superantigens as Toxins
Special type of Exotoxin
Nonspecifically stimulate T-cells.
 Intense immune response due to
release of cytokines.
 Fever, nausea, vomiting,
diarrhea, shock,
and death.
Representative Examples of Exotoxins
Bacterial Species
Exotoxin
C. diphtheriae
A-B toxin
S. pyogenes
Membrane-disrupting
erythrogenic toxin
C. botulinum
A-B toxin; neurotoxin
C. tetani
A-B toxin; neurotoxin
V. cholerae
A-B toxin; enterotoxin
S. aureus
Superantigen
Endotoxins
 Bacterial cell death, antibiotics, and antibodies may
cause the release of endotoxins.
 Endotoxins cause fever (by inducing the release of
interleukin-1) and shock (because of a TNF-induced
decrease in blood pressure).
 TNF release also allows bacteria to cross BBB.
 The LAL assay (Limulus amoebocyte lysate) is used to
detect endotoxins in drugs and on medical devices.
Fig 15.6
Endotoxin Summary
Source:
Relation to
microbe:
Chemistry:
Gram –
Present in LPS of outer
membrane
_____________________
Fever?
Neutralized by
antitoxin?
Yes
LD50:
Relatively large
_______
Pathogenic Properties
of Viruses
Evasion of IS by
 Growing inside cells
 Rabies virus spikes
mimic ACh
 HIV hides attachment site  CD4 long and slender
Visible effects of viral infection = Cytopathic
Effects
1. cytocidal (cell death)
2. noncytocidal effects (damage but not death).
Pathogenic Properties of Fungi
 Fungal waste products
may cause symptoms
Fungal Toxins
 Chronic infections provoke
allergic responses
 Ergot toxin
 Proteases
 Aflatoxin
 Candida, Trichophyton
 Capsule prevents
phagocytosis
 Cryptococcus
 Claviceps purpurea
 Aspergillus flavus
Pathogenic Properties of Protozoa & Helminths
 Presence of protozoa
 Protozoan waste products may cause symptoms
 Avoid host defenses by
 Growing in phagocytes
 Antigenic variation
 Presence of helminths interferes
with host function
 Helminths metabolic waste
can cause symptoms
Wuchereria bancrofti
Portals of Exit
 Respiratory tract:
Coughing and sneezing
 Gastrointestinal tract:
Feces and saliva
 Genitourinary tract:
Urine and vaginal
secretions
 Skin
 Blood: Biting
arthropods and
needles or syringes
Microbial Mechanisms of Pathogenicity Overview
Foundation Fig 15.9