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Microbial Mechanisms of
Pathogenicity
Infection and Disease
A. Definitions
B. Generalized Stages of Infection
C. Virulence Factors and Toxins
A. Definitions
 Disease and Infectious Disease
• Disease
• Any deviation from a condition of good
health and well-being
• Infectious Disease
 A disease condition caused by the presence
or growth of infectious microorganisms or
parasites
A. Definitions
 Pathogenicity and Virulence
• Pathogenicity
• The ability of a microbe to cause disease
• This term is often used to describe or compare
species
• Virulence
• The degree of pathogenicity in a microorganism
• This term is often used to describe or compare
strains within a species
Definitions
 Acute infection vs. chronic infection
• Acute Infection
• An infection characterized by sudden onset,
rapid progression, and often with severe
symptoms
• Chronic Infection
• An infection characterized by delayed onset
and slow progression
Definitions
 Primary infection vs. secondary infection
• Primary Infection
• An infection that develops in an otherwise
healthy individual
• Secondary Infection
• An infection that develops in an individual
who is already infected with a different
pathogen
Definitions
 Localized infection vs. systemic infection
• Localized Infection
• An infection that is restricted to a specific
location or region within the body of the host
• Systemic Infection
• An infection that has spread to several
regions or areas in the body of the host
Definitions
 Clinical infection vs. subclinical infection
• Clinical Infection
• An infection with obvious observable or
detectable symptoms
• Subclinical Infection
• An infection with few or no obvious
symptoms
Definitions
 Opportunistic infection
• An infection caused by microorganisms that are
commonly found in the host’s environment.
This term is often used to refer to infections
caused by organisms in the normal flora.
Definitions
 The suffix “-emia”
• A suffix meaning “presence of an infectious agent”
• Bacteremia = Presence of infectious bacteria
• Viremia = Presence of infectious virus
• Fungemia = Presence of infectious fungus
• Septicemia = Presence of an infectious agent in
the bloodstream
Definitions
 The suffix “-itis”
• A suffix meaning “inflammation of”
• Examples:
–Pharyngitis = Inflammation of the pharynx
–Endocarditis = Inflammation of the heart
chambers
–Gastroenteritis = Inflammation of the
gastointestinal tract
Definitions
 Epidemiology
• The study of the transmission of disease
 Communicable Disease
• A disease that can be transmitted from one
individual to another
 Noncommunicable Disease
• A disease that is not transmitted from one
individual to another
Definitions
 Endemic Disease
• A disease condition that is normally found in a
certain percentage of a population
 Epidemic Disease
• A disease condition present in a greater than
usual percentage of a specific population
 Pandemic Disease
• An epidemic affecting a large geographical
area; often on a global scale
Definitions
 Reservoir of Infection
• The source of an infectious agent
 Carrier
• An individual who carries an infectious agent
without manifesting symptoms, yet who can
transmit the agent to another individual
 Fomites
• Any inanimate object capable of being an
intermediate in the indirect transmission of an
infectious agent
Definitions
• Animal Vectors
• An animal (nonhuman) that can transmit an
infectious agent to humans
• Two types: mechanical and biological
• Mechanical animal vectors: The infectious agent is
physically transmitted by the animal vector, but the agent
does not incubate or grow in the animal; e.g, the
transmission of bacteria sticking to the feet of flies
• Biological animal vectors: The infectious agent must
incubate in the animal host as part of the agent’s
developmental cycle; e.g, the transmission of malaria
by infected mosquitoes
Definitions
 Direct Mechanisms of Disease Transmission
• Directly From Person to Person
• Examples:
Direct Skin Contact
Airborne (Aerosols)
Definitions
 Indirect Mechanisms of Disease Transmission
• Examples:
Food & Waterborne Transmission
Fomites
Animal Vectors
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, infectious disease results!
Molecular Determinants of Pathogenicity
Production
and delivery
of various
factors
Attachment
to host
tissues
Replication
and evasion
of immunity
Damage to
host tissues
Microbial Mechanisms of Pathogenicity:
How Microorganisms Cause Disease
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
 Common cold
 Flu
 Tuberculosis
 Whooping cough
 Pneumonia
 Measles
 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
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 through
openings in the skin: hair follicles and sweat
glands, wound …etc
3rd Portal of Entry: Parentarel
 Microorganisms are deposited into the
tissues below the skin or mucus membranes
 Punctures and scratches
 injections
 bites
 surgery
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
Some cells use fimbriae to
adhere.
Fimbriae can play
a role in tissue
tropism. Example -
attachment of Candida
to vaginal epithelial
cells
Adhesins and ligands are usually
on Fimbriae
 Neisseria gonorrhoeae
 ETEC
(Entertoxigenic E. coli)
 Bordetello pertussis
Bacteria typically employ proteins known as Adhesins to
attach to host tissues, which usually are located on ends of
fimbriae.
Alternatively, adhesins can consist of glycocalyx.
2. Capsules
 Prevent phagocytosis
 attachment
 Streptococcus
pneumoniae
 Klebsiella pneumoniae
 Haemophilus
influenzae
 Bacillus anthracis
 Streptococcus mutans
K. pneumoniae
Avoidance of Phagocytosis
Capsules are Involved in
avoidance of phagocyte-
mediated recognition
and attachment.
Cell Wall Components
M protein: Found on cell surface and
fimbriae of Streptococcus pyogenes.
Mediates attachment and helps resist
phagocytosis. M-protein is heat and
acid resistant
Waxes [ Mycolic Acid]: In cell wall
of Mycobacterium tuberculosis helps
resist digestion after phagocytosis and
can multiply inside WBC.
3. Enzymes
 Many pathogens secrete enzymes that
contribute to their pathogenicity
Enzymes and toxins that harm eukaryotic cells.
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 (α) Hemolytic Streptococci
- secrete hemolysins that cause the incomplete
lysis or RBC’s
Incomplete
Lysis of RBC
2. Beta (β) Hemolytic Streptococci
- secrete hemolysins that cause the complete lysis
of RBC’s
Complete
Lysis of RBC
3. Gamma (γ) 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
 Staphylococcus aureus - are often coagulase
positive
Fibrinogen ----------------- Fibrin ( Clot)
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
through a body tissue
 Streptococci, Staphylococci, Clostridia and
pneumococci.
F. Collagenase
 Breaks down collagen (found in many connective
tissues)
 Clostridium perfringens - Gas Gangrene
• uses this to spread through muscle tissue
Severe gangrene caused by Clostridium perfringens.
Source: Tropical Medicine and Parasitology, 1997
Tissue Damage Caused by Microbial
Enzymes of Clostridium perfringens
G. Necrotizing Factor
- causes death (necrosis) to tissue cells
“Flesh Eating Bacteria”
Necrotizing fasciitis
H. Lecithinase
 Destroys lecithin ( phosphatidylcholine)
component of plasma membrane.
 Allowing pathogen to spread
 Clostridium perfringens
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 H. Lecithinase
4. Toxins
 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
• Toxigenicity: Capacity of microorganisms to
produce toxins.
Two Types of Toxins
 1. Exotoxins
• secreted outside the bacterial cell
 2. Endotoxins
• part of the outer cell wall of Gram (-) bacteria.
??
Exotoxins versus Endotoxins
I- Exotoxins
 Mostly seen in Gram (+) Bacteria
 Most gene that code for exotoxins are
located on plasmids or phages
Three Types of Exotoxins
 1. Cytotoxins
• kill cells e.g. Diphtheria toxin
 2. Neurotoxins
• interfere with normal nerve impulses.e.g.
Botulinum Toxin
 3. Enterotoxins
• effect cells lining the G.I. Tract. e.g. Cholera
toxin or choleragen.
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 - modified toxin by heat, chemical,
radiation, that have lost their toxicity. 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 in Jordan
 1. Diphtheria
 2. Pertussis
 3. Tetanus
 4. Measles
 5. Mumps
 6. Rubella
• German Measles
 7. Polio
 9. Hepatitis B
 Corynebacterium diphtheriae
 Bordetello pertussis
 Clostridium tetani
 Measles virus
 Mumps virus
 Rubella virus
 Polio virus
 Hepatitis B Virus
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
 cytotoxin - damages blood capillaries and results in a
skin rash
• Strep Thoat with a rash
Rash of Scarlet Fever Caused by Erythrogenic
Toxins of Streptococcus pyogenes
Diseases Caused by Staphylococcal Toxins
Scalded Skin Syndrome Toxic Shock Syndrome
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”
Neonatal Tetanus (Wrinkled brow and risus sardonicus)
Source: Color Guide to Infectious Diseases, 1992
Muscle Spasms of Tetanus are Caused by
Neurotoxin of Clostridium tetani
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)
 Two polypeptides: A (active) and B (binding).
The A subunit of enterotoxin causes epithelial
cells to discharge large amounts of fluids and
electrolytes.
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
Rice-water stool of cholera. The A subunit of enterotoxin causes
epithelial cells to discharge large amounts of fluids and electrolytes.
Source: Tropical Medicine and Parasitology, 1995
Vibrio Enterotoxin Causes Profuse Watery Diarrhea
EHEC (Enterohemorrhagic E. coli)
 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)
More
on
Toxins
II- Endotoxins
• Part of outer membrane surrounding gram-negative
bacteria.
• Endotoxin is lipid portion of lipopolysaccharides (LPS),
called lipid A.
• Effect exerted when gram-negative cells die and cell
walls undergo lysis, liberating endotoxin.
• All produce the same signs and symptoms:
• Chills, fever, weakness, general aches, blood clotting
and tissue death, shock, and even death. Can also
induce miscarriage.
• Fever: Pyrogenic response is caused by endotoxins.
Exotoxins vs. Endotoxins
Endotoxin is LPS
Endotoxins (Continued)
• Endotoxins do not promote the formation of
effective antibodies.
• Organisms that produce endotoxins include:
• Salmonella typhi
• Proteus spp.
• Pseudomonas spp.
• Neisseria spp.
• Medical equipment that has been sterilized may
still contain endotoxins.
• Limulus amoebocyte assay (LAL) is a test used to
detect tiny amounts of endotoxin.
Events leading to fever:
• Gram-negative bacteria are digested by
phagocytes.
• LPS is released by digestion in vacuoles, causing
macrophages to release interleukin-1 (IL-1).
• IL-1 is carried via blood to hypothalamus, which
controls body temperature.
• IL-1 induces hypothalamus to release
prostaglandins, which reset the body’s
thermostat to higher temperature.
Microbial Mechanisms of Pathogenicity:
How Microorganisms Cause Disease
III. B. The Normal Flora of
Humans
 Types of Symbiosis
• Mutualism
• A symbiotic relationship in which both
species benefit
• Commensalism
• A symbiotic relationship in which one
species benefits, and the other species is
neither helped nor harmed
III. B. The Normal Flora of
Humans
 Types of Symbiosis (cont.)
• Parasitism
• A symbiotic relationship in which one
species benefits, and the other species is
harmed
• Generally, the species that benefits (the
parasite) is much smaller than the species
that is harmed (the host)
III. B. The Normal Flora of
Humans
 Normal flora is present in
• skin
• upper respiratory tract
• oral cavity
• intestine, especially large intestine
• vaginal tract
 Very little normal flora in eyes & stomach
III. B. The Normal Flora of
Humans
 Notably absent in most all internal organs
• Absent in:
• lower respiratory tract
• muscle tissue
• blood & tissue fluid
• cerebrospinal fluid
• peritoneum
• pericardium
• meninges
III. B. The Normal Flora of
Humans
 Benefits of the normal flora
• Nutrient production/processing
eg Vitamin K production by E. coli
• Competition with pathogenic microbes
• Normal development of the immune system
 Normal flora and opportunistic infections
III. C. Generalized Stages of
Infection
1. Entry of Pathogen
• Portal of Entry
2. Colonization
• Usually at the site of entry
3. Incubation Period
• Asymptomatic period
• Between the initial contact with the microbe
and the appearance of the first symptoms
III. C. Generalized Stages of
Infection
4. Prodromal Symptoms
• Initial Symptoms
5. Invasive period
• Increasing Severity of Symptoms
• Fever
• Inflammation and Swelling
• Tissue Damage
• Infection May Spread to Other Sites
III. C. Generalized Stages of
Infection
6. Decline of Infection
5. Convalescence
Course of Infectious Disease
Incubation period is
the interval between
exposure and
illness onset.
Convalescence is
a time of
recuperation and
recovery from
illness.
Depending on various
factors an individual may
still be infectious during
either incubation or
convalescence.
Lecture 6- Bacteria- Pathathogenesis.ppt

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  • 2. Infection and Disease A. Definitions B. Generalized Stages of Infection C. Virulence Factors and Toxins
  • 3. A. Definitions  Disease and Infectious Disease • Disease • Any deviation from a condition of good health and well-being • Infectious Disease  A disease condition caused by the presence or growth of infectious microorganisms or parasites
  • 4. A. Definitions  Pathogenicity and Virulence • Pathogenicity • The ability of a microbe to cause disease • This term is often used to describe or compare species • Virulence • The degree of pathogenicity in a microorganism • This term is often used to describe or compare strains within a species
  • 5. Definitions  Acute infection vs. chronic infection • Acute Infection • An infection characterized by sudden onset, rapid progression, and often with severe symptoms • Chronic Infection • An infection characterized by delayed onset and slow progression
  • 6. Definitions  Primary infection vs. secondary infection • Primary Infection • An infection that develops in an otherwise healthy individual • Secondary Infection • An infection that develops in an individual who is already infected with a different pathogen
  • 7. Definitions  Localized infection vs. systemic infection • Localized Infection • An infection that is restricted to a specific location or region within the body of the host • Systemic Infection • An infection that has spread to several regions or areas in the body of the host
  • 8. Definitions  Clinical infection vs. subclinical infection • Clinical Infection • An infection with obvious observable or detectable symptoms • Subclinical Infection • An infection with few or no obvious symptoms
  • 9. Definitions  Opportunistic infection • An infection caused by microorganisms that are commonly found in the host’s environment. This term is often used to refer to infections caused by organisms in the normal flora.
  • 10. Definitions  The suffix “-emia” • A suffix meaning “presence of an infectious agent” • Bacteremia = Presence of infectious bacteria • Viremia = Presence of infectious virus • Fungemia = Presence of infectious fungus • Septicemia = Presence of an infectious agent in the bloodstream
  • 11. Definitions  The suffix “-itis” • A suffix meaning “inflammation of” • Examples: –Pharyngitis = Inflammation of the pharynx –Endocarditis = Inflammation of the heart chambers –Gastroenteritis = Inflammation of the gastointestinal tract
  • 12. Definitions  Epidemiology • The study of the transmission of disease  Communicable Disease • A disease that can be transmitted from one individual to another  Noncommunicable Disease • A disease that is not transmitted from one individual to another
  • 13. Definitions  Endemic Disease • A disease condition that is normally found in a certain percentage of a population  Epidemic Disease • A disease condition present in a greater than usual percentage of a specific population  Pandemic Disease • An epidemic affecting a large geographical area; often on a global scale
  • 14. Definitions  Reservoir of Infection • The source of an infectious agent  Carrier • An individual who carries an infectious agent without manifesting symptoms, yet who can transmit the agent to another individual  Fomites • Any inanimate object capable of being an intermediate in the indirect transmission of an infectious agent
  • 15. Definitions • Animal Vectors • An animal (nonhuman) that can transmit an infectious agent to humans • Two types: mechanical and biological • Mechanical animal vectors: The infectious agent is physically transmitted by the animal vector, but the agent does not incubate or grow in the animal; e.g, the transmission of bacteria sticking to the feet of flies • Biological animal vectors: The infectious agent must incubate in the animal host as part of the agent’s developmental cycle; e.g, the transmission of malaria by infected mosquitoes
  • 16. Definitions  Direct Mechanisms of Disease Transmission • Directly From Person to Person • Examples: Direct Skin Contact Airborne (Aerosols)
  • 17. Definitions  Indirect Mechanisms of Disease Transmission • Examples: Food & Waterborne Transmission Fomites Animal Vectors
  • 18.
  • 19. 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, infectious disease results!
  • 20. Molecular Determinants of Pathogenicity Production and delivery of various factors Attachment to host tissues Replication and evasion of immunity Damage to host tissues
  • 21. Microbial Mechanisms of Pathogenicity: How Microorganisms Cause Disease
  • 22. Portals of Entry  1. Mucus Membranes  2. Skin  3. Parentarel
  • 23. 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
  • 24. Common Diseases contracted via the Respiratory Tract  Common cold  Flu  Tuberculosis  Whooping cough  Pneumonia  Measles  Diphtheria
  • 25. 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
  • 26. Common diseases contracted via the G.I. Tract  Salmonellosis • Salmonella sp.  Shigellosis • Shigella sp.  Cholera • Vibrio cholorea  Ulcers • Helicobacter pylori  Botulism • Clostridium botulinum Clostridium botulinum
  • 27. 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.
  • 28. Mucus Membranes of the Genitourinary System - STD’s Gonorrhea Neisseria gonorrhoeae Syphilis Treponema pallidum Chlamydia Chlamydia trachomatis HIV Herpes Simplex II
  • 29. Mucus Membranes  D. Conjunctiva – • mucus membranes that cover the eyeball and lines the eyelid  Trachoma • Chlamydia trachomatis
  • 30. 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 through openings in the skin: hair follicles and sweat glands, wound …etc
  • 31.
  • 32. 3rd Portal of Entry: Parentarel  Microorganisms are deposited into the tissues below the skin or mucus membranes  Punctures and scratches  injections  bites  surgery
  • 33. 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
  • 34. 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
  • 35. 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 ????
  • 36. How do Bacterial Pathogens penetrate Host Defenses? 1. Adherence - almost all pathogens have a means to attach to host tissue Binding Sites adhesins ligands
  • 37. Some cells use fimbriae to adhere. Fimbriae can play a role in tissue tropism. Example - attachment of Candida to vaginal epithelial cells
  • 38. Adhesins and ligands are usually on Fimbriae  Neisseria gonorrhoeae  ETEC (Entertoxigenic E. coli)  Bordetello pertussis
  • 39. Bacteria typically employ proteins known as Adhesins to attach to host tissues, which usually are located on ends of fimbriae. Alternatively, adhesins can consist of glycocalyx.
  • 40. 2. Capsules  Prevent phagocytosis  attachment  Streptococcus pneumoniae  Klebsiella pneumoniae  Haemophilus influenzae  Bacillus anthracis  Streptococcus mutans K. pneumoniae
  • 41. Avoidance of Phagocytosis Capsules are Involved in avoidance of phagocyte- mediated recognition and attachment.
  • 42. Cell Wall Components M protein: Found on cell surface and fimbriae of Streptococcus pyogenes. Mediates attachment and helps resist phagocytosis. M-protein is heat and acid resistant Waxes [ Mycolic Acid]: In cell wall of Mycobacterium tuberculosis helps resist digestion after phagocytosis and can multiply inside WBC.
  • 43. 3. Enzymes  Many pathogens secrete enzymes that contribute to their pathogenicity
  • 44. Enzymes and toxins that harm eukaryotic cells.
  • 45. 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
  • 46. B. Hemolysins - cause the lysis of RBC’s Streptococci
  • 47. 1. Alpha (α) Hemolytic Streptococci - secrete hemolysins that cause the incomplete lysis or RBC’s Incomplete Lysis of RBC
  • 48. 2. Beta (β) Hemolytic Streptococci - secrete hemolysins that cause the complete lysis of RBC’s Complete Lysis of RBC
  • 49. 3. Gamma (γ) Hemolytic Streptococci - do not secrete any hemolysins
  • 50. C. Coagulase - cause blood to coagulate  Blood clots protect bacteria from phagocytosis from WBC’s and other host defenses  Staphylococcus aureus - are often coagulase positive Fibrinogen ----------------- Fibrin ( Clot)
  • 51. 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)
  • 52. E. Hyaluronidase  Breaks down Hyaluronic acid (found in connective tissues)  “Spreading Factor”  mixed with a drug to help spread the drug through a body tissue  Streptococci, Staphylococci, Clostridia and pneumococci.
  • 53. F. Collagenase  Breaks down collagen (found in many connective tissues)  Clostridium perfringens - Gas Gangrene • uses this to spread through muscle tissue
  • 54. Severe gangrene caused by Clostridium perfringens. Source: Tropical Medicine and Parasitology, 1997 Tissue Damage Caused by Microbial Enzymes of Clostridium perfringens
  • 55. G. Necrotizing Factor - causes death (necrosis) to tissue cells “Flesh Eating Bacteria” Necrotizing fasciitis
  • 56. H. Lecithinase  Destroys lecithin ( phosphatidylcholine) component of plasma membrane.  Allowing pathogen to spread  Clostridium perfringens
  • 57. 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 H. Lecithinase
  • 58. 4. Toxins  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 • Toxigenicity: Capacity of microorganisms to produce toxins.
  • 59. Two Types of Toxins  1. Exotoxins • secreted outside the bacterial cell  2. Endotoxins • part of the outer cell wall of Gram (-) bacteria. ??
  • 61.
  • 62. I- Exotoxins  Mostly seen in Gram (+) Bacteria  Most gene that code for exotoxins are located on plasmids or phages
  • 63. Three Types of Exotoxins  1. Cytotoxins • kill cells e.g. Diphtheria toxin  2. Neurotoxins • interfere with normal nerve impulses.e.g. Botulinum Toxin  3. Enterotoxins • effect cells lining the G.I. Tract. e.g. Cholera toxin or choleragen.
  • 64. 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 - modified toxin by heat, chemical, radiation, that have lost their toxicity. Injected to stimulate the production of antitoxins and provide immunity.
  • 65. Example: DPT Vaccine  D - Diphtheria • Corynebacterium diphtheriae  P - Pertussis • Bordetello pertussis  T - Tetanus • Clostridium tetani DPT - Diphtheria Toxoid Pertussis Antigen Tetanus Toxoid
  • 66. Required Immunizations in Jordan  1. Diphtheria  2. Pertussis  3. Tetanus  4. Measles  5. Mumps  6. Rubella • German Measles  7. Polio  9. Hepatitis B  Corynebacterium diphtheriae  Bordetello pertussis  Clostridium tetani  Measles virus  Mumps virus  Rubella virus  Polio virus  Hepatitis B Virus
  • 67. 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
  • 68. Lysogenic Convergence  Scarlet Fever  Streptococcus pyogenes • lysogenic convergence  cytotoxin - damages blood capillaries and results in a skin rash • Strep Thoat with a rash
  • 69. Rash of Scarlet Fever Caused by Erythrogenic Toxins of Streptococcus pyogenes
  • 70. Diseases Caused by Staphylococcal Toxins Scalded Skin Syndrome Toxic Shock Syndrome
  • 71. 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
  • 72. 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”
  • 73. Neonatal Tetanus (Wrinkled brow and risus sardonicus) Source: Color Guide to Infectious Diseases, 1992 Muscle Spasms of Tetanus are Caused by Neurotoxin of Clostridium tetani
  • 74. Diseases caused by Enterotoxins  Cholera • Vibrio cholerae • Gram (-) comma shaped rods
  • 75. 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)  Two polypeptides: A (active) and B (binding). The A subunit of enterotoxin causes epithelial cells to discharge large amounts of fluids and electrolytes.
  • 76. 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
  • 77. Rice-water stool of cholera. The A subunit of enterotoxin causes epithelial cells to discharge large amounts of fluids and electrolytes. Source: Tropical Medicine and Parasitology, 1995 Vibrio Enterotoxin Causes Profuse Watery Diarrhea
  • 78. EHEC (Enterohemorrhagic E. coli)  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)
  • 80. II- Endotoxins • Part of outer membrane surrounding gram-negative bacteria. • Endotoxin is lipid portion of lipopolysaccharides (LPS), called lipid A. • Effect exerted when gram-negative cells die and cell walls undergo lysis, liberating endotoxin. • All produce the same signs and symptoms: • Chills, fever, weakness, general aches, blood clotting and tissue death, shock, and even death. Can also induce miscarriage. • Fever: Pyrogenic response is caused by endotoxins.
  • 83. Endotoxins (Continued) • Endotoxins do not promote the formation of effective antibodies. • Organisms that produce endotoxins include: • Salmonella typhi • Proteus spp. • Pseudomonas spp. • Neisseria spp. • Medical equipment that has been sterilized may still contain endotoxins. • Limulus amoebocyte assay (LAL) is a test used to detect tiny amounts of endotoxin.
  • 84. Events leading to fever: • Gram-negative bacteria are digested by phagocytes. • LPS is released by digestion in vacuoles, causing macrophages to release interleukin-1 (IL-1). • IL-1 is carried via blood to hypothalamus, which controls body temperature. • IL-1 induces hypothalamus to release prostaglandins, which reset the body’s thermostat to higher temperature.
  • 85. Microbial Mechanisms of Pathogenicity: How Microorganisms Cause Disease
  • 86. III. B. The Normal Flora of Humans  Types of Symbiosis • Mutualism • A symbiotic relationship in which both species benefit • Commensalism • A symbiotic relationship in which one species benefits, and the other species is neither helped nor harmed
  • 87. III. B. The Normal Flora of Humans  Types of Symbiosis (cont.) • Parasitism • A symbiotic relationship in which one species benefits, and the other species is harmed • Generally, the species that benefits (the parasite) is much smaller than the species that is harmed (the host)
  • 88. III. B. The Normal Flora of Humans  Normal flora is present in • skin • upper respiratory tract • oral cavity • intestine, especially large intestine • vaginal tract  Very little normal flora in eyes & stomach
  • 89. III. B. The Normal Flora of Humans  Notably absent in most all internal organs • Absent in: • lower respiratory tract • muscle tissue • blood & tissue fluid • cerebrospinal fluid • peritoneum • pericardium • meninges
  • 90. III. B. The Normal Flora of Humans  Benefits of the normal flora • Nutrient production/processing eg Vitamin K production by E. coli • Competition with pathogenic microbes • Normal development of the immune system  Normal flora and opportunistic infections
  • 91. III. C. Generalized Stages of Infection 1. Entry of Pathogen • Portal of Entry 2. Colonization • Usually at the site of entry 3. Incubation Period • Asymptomatic period • Between the initial contact with the microbe and the appearance of the first symptoms
  • 92. III. C. Generalized Stages of Infection 4. Prodromal Symptoms • Initial Symptoms 5. Invasive period • Increasing Severity of Symptoms • Fever • Inflammation and Swelling • Tissue Damage • Infection May Spread to Other Sites
  • 93. III. C. Generalized Stages of Infection 6. Decline of Infection 5. Convalescence
  • 94. Course of Infectious Disease Incubation period is the interval between exposure and illness onset. Convalescence is a time of recuperation and recovery from illness. Depending on various factors an individual may still be infectious during either incubation or convalescence.