Bacterial Phathogenesis and associated notes .ppt

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1. Microbial Mechanisms
of Pathogenicity

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

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

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
•LD
50 - Lethal Dose of a microbes toxin
that will kill 50% of experimentally
inoculated test animal
•ID
50 - infectious dose required to cause
disease in 50% of inoculated test animals
–Example: ID
50 for Vibrio cholerea 10
8
cells
(100,000,000 cells)
–ID
50 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. ??

60. Exotoxins versus Endotoxins

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. 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

67. Lysogenic Convergence
•Scarlet Fever
•Streptococcus pyogenes
– lysogenic convergence
•cytotoxin - damages blood capillaries
and results in a skin rash
–Strep Thoat with a rash

68. Rash of Scarlet Fever Caused by Erythrogenic
Toxins of Streptococcus pyogenes

69. Diseases Caused by Staphylococcal Toxins
Scalded Skin Syndrome Toxic Shock Syndrome

70. 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

71. 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”

72. 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

73. Diseases caused by
Enterotoxins
Cholera
–Vibrio cholerae
–Gram (-) comma shaped rods

74. Cholera toxin
Converts ATP into cAMP
causes cells to excrete Cl
-
ions and
inhibits absorption of Na
+
ions
Electrolyte imbalance
H
2O leaves by osmosis
H
2O 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.

75. 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

76. 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

77. 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)

78. M
o
r
e

o
n

T
o
x
in
s

79. 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.

80. Exotoxins vs. Endotoxins

81. Endotoxin is LPS

82. 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.

83. 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.

84. Microbial Mechanisms of Pathogenicity:
How Microorganisms Cause Disease

85. 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

86. 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)

87. 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

88. 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

89. 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

90. 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

91. 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

92. III. C. Generalized Stages of Infection
6.Decline of Infection
5.Convalescence

93. 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.