medical Microbiology lecture power point ppt bacterial infection and pathogenesis

1. Bacterial Infection and
Pathogenesis

2. • pathogenesis (how a disease develops)
• pathogenicity (disease­causing ability of
microorganisms)
• virulence (degree of pathogenicity)

3. Section 1 Normal flora
Microorganisms that
live on or in human
bodies, and ordinarily
do not cause human
diseases

4. – Mechanisms
• Competition for receptors on host cells
• Competition for nutrients
• Metabolic or toxic products
• Nutritional function
• Immunity
The medical significance of
normal flora
• Antagonism

5. normal flora that, under ordinary
circumstances, cause no harm but can
cause disease under certain conditions
Opportunistic pathogen

6. • Alteration of colonization sites
• Declination of the host immunity defense
• Dysbacteriosis
– the state in which the proportion of bacterial
species and the number of the normal flora
colonizing in a certain site of a host present
large­scale alteration
Under what conditions will opportunistic
pathogens cause human diseases?

7. Section 2 Bacterial infection
bacteriabacteria
Immune status
of the host
inbodyouterbody
细菌细菌
细菌细菌
细菌细菌
bacteriabacteria
bbacteriaacteria
bacteriabacteria
bacteriabacteria
toxins
Causedisease

8. Why do people get infectious diseases?
From the organism’s perspectives
The number of organisms
The virulence of these organisms
From the host’s perspective
Innate immunity
acquired immunity
Antibody-mediated
cell-mediated

9. Pathogenicity of bacteria
 Pathogenicity and virulence: refer to an
organism's ability to cause disease.
 LD50 (median lethal dose) or ID50 (median
infectious dose): refers to the number of
bacteria or amount of bacterial products, such
as toxins, that cause death or bacterial disease
in 50% of animals in a defined period after the
bacteria are administrated by a designated
route.

10. Pathogenicity of bacteria
 pathogenicity （ decide by):
 virulence factors of the bacterium
 the number of infecting bacteria
 route of entry into the body

11. Portals of Entry and the size of the
inoculum
 If certain pathogen enter the wrong portal,they will
not be infectious.
 Occasionally,an infective agent can enter by more
than one portal.e.g.mycobacterium tuberculosis.

12. Portals of entry
 skin
 respiratory system
 ingestion system
 genitourinary system
C. tetani

13. The size of the inoculum
 The quantity of microbes in the inoculating dose.

14. The originate and progress of infection
 A.The source of the infection
 B.routes of pathogen transmission
 C.Patterns of infection

15. A.The source of infection
 Living reservoirs
Persons or animals with frank symptomatic
infection are obvious sources of infection
 Nonliving reservoirs

16.  Exogenous infections:
 Patients
 Carriers: those in whom pathogens are
present and may be multiplying, but who
shows no clinical response to their
presence.
 Contaminated animals
 Endogenous infections
Sources of infectious diseases

17.  Carrier state
 Definition of carriers: those in whom pathogens
are present and may be multiplying, but who
shows no clinical response to their presence
 Definition of carrier state: a type of infections
causing no signs of symptoms, in which
pathogens multiply and may be transmitted to
other individuals

18.  two major types of carrier:
Convalescent carriers: those who recover from
infectious disease and in whom the pathogens remain
and multiply without causing overt symptoms.
Healthy carriers: those who do not have the clinical
symptoms but carry pathogens indeed.
Typhoid Mary (Mary Mallon) 社会恶习的扩散者

19. B. Routes of pathogen
transmission
 1.respiratory infections: the tiny particles of
liquid released into the air form aerosols or
droplets
 2.wound infectons: in soil and feces of
human and animal
 3.intestinal infections: contaminate drinking
water and food or when used to fertilize
crops

20.  4.contact infection:directly contact between
the skin and mucous membranes of the
infected person or animal and that of healthy
person
 5.animal bites infections:the majority of
animal vectors are arthropods such as
fleas,mosquitos,flies,and ticks

21. acute infection
chronic infection
C. Patterns of infection
Apparent infection
1.apparent infection
When an infection causes pathological changes
leading to disease,it is often accompanied by a
variety of signs and symptoms
Infectons that come on rapidly,with severe but short-
lived effects,are called acute infections
The infection persists several months to several
years called chronic infection

22.  Inapparent infection: also called
subclinical infection that has no
detectable clinical symptoms

23. local infection
generalized/systemic infection
Localized infection stands for the case that the
microbe enters the body and remains confined to a
specific tissue

24. Generalized infection
 Bacteremia
 Definition: a transitory disease in which bacteria present in
the blood are usually cleared from the vascular system with
no harmful effects.
 Septicemia
 Definition: a disease in which the blood serves as a site of
bacterial multiplication as well as a means of transfer of the
infectious agent from one site to another.

25.  Toxemia
 Definition: the presence of microbial toxins
in the blood
 Pyemia
 Definition: the presence of pyogenic bacteria
in the blood as they are being spread from
one site to another in the body

26. 毒
素
血液
毒
素
toxintoxin
special toxic
symptom
e.g.tetanus
Toxemia
局
部
病
灶
局
部
病
灶
pathogenic bacterium
can grow in blood
BacteremiaBacteremia
Defense function↓↓
毒素毒素毒素毒素毒素毒素toxin
Organism is
seriously damaged,
toxic symptom all over
the body 。
Septicemia
Local lesion

27. blood
局
部
病
灶
局
部
病
灶
毒素toxin
毒
素
毒
素
toxin
New pyosis focus of
infection
Pyosepticemia
When Pyosis bacteria
cause Septicemia ，
multiple pyosis focus
of infection will
happen.e.g.
staphylococci aureus

28. A microorganism that causes disease
Pathogen
Section 3. Bacterial pathogenicity

29. • Virulence
• The amount of entry
• The portal of entry
What factors determine
bacterial pathogenicity?

30. What is virulence
The ability of any agent of infection to
produce disease. The virulence of a
microorganism (such as a bacterium or virus)
is the measurement of the severity of the
capable of disease.
Invasiveness
Toxin
Virulence

31. 1. Invasiveness
Definition
The ability of microorganisms to enter the
body and spread in the tissues.

32. Invasiveness
• Adherence factor
– Pilus
– LTA
• Capsule
• Invasive enzyme

33. 1.1 Material foundation of invasiveness
1.1.1 Adherence factor( 粘附因子 )
Definition of adherence:
The process by which bacteria stick to the
surfaces of host cells. Once bacteria have entered the
body, adherence is a major initial step in the infection
process. It is a general cellular microbiology
phenomenon take place at the early stage of infection.
The terms adherence, adhesion or attachment are
often used interchangeably

34. 1.2 Adherent mechanisms
Electrostatic attraction( 静 吸引电 )
Hydrophobic interaction ( 疏水作用 )
Cationic bridge( 子阳离 桥联 )
Nonspecific adherence
ligand-receptor( 配体 - 受体 )bonding Specific adherence
(Reversible)
(Irreversible )

37. Microbe Adhesin Receptor
S. Aureus LTA Unknown
S. epidermidis Slime Unknown
Streptococcus, group A LTA-M protein
complex
Fibronectin
S. pneumoniae Surface protein N-acetylhexosamine-gal
E. coli Type 1 fimbriae d-Mannose
Colonization factor
antigen fimbriae
GM1 ganglioside
P fimbriae P blood group glycolipid
Other Enterobacteriaceae Type 1 fimbriae d-Mannose
N. gonorrhoeae Fimbriae GD1
ganglioside
T. pallidum P1
, P2
, P3
Fibronectin
Chlamydia sp. Cell surface lectin N-acetylglucosamine
M. pneumoniae Protein P1 Sialic acid
V. cholerae Type 4 pili Fucose and mannose
Examples of Bacterial Adherence Mechanisms

38. Examples of tissue tropism for bacterial infection
Bacteria TissueTissue
N. meningitidis Nasopharynx epithelium 、、 blood vessel endothelium
N. gonorrhoeae Urethro-epithelium
V. cholerae Enteric epithelium
B. pertussis Respiratory epithelium
H. pylori Gastric mucosa
Group A Streptococcus Nasopharynx epithelium
C. Jejuni Enteric epithelium
M. Pneumoniae Respiratory epithelium

39. Tissue tropism
Different bacteria adhere to different
host cell by different ligand

40. 1.3 Invasive mechanisms
1.3.1 Capsule and microcapsule
1.3.2 Invasive EnzymeInvasive Enzyme(( 侵 性袭 酶类侵 性袭 酶类 ))

41. 1.3.3 Microcolony( 微菌落 ) and biofilm( 生物膜 )
1.3.3.1 Microcolony
By microcolony we mean a colony of bacteria
visible only under a low power microscope, and its
formation is an event preceding mature of biofilm
formation.

42. Microcolony( 微菌落 )

43. Bacterial biofilms are highly interactive, ubiquitous
bacterial ecosystems consisting of individual bacterium
bound to a foreign surface by complex matrix of
extracellular polysaccharides. They can be thought of as
“bacterial communities or cities.” Within these
communities live groups of bacteria constituting multiple
species. Individual bacterium coalesce by linking
extracellular polysaccharides on their cell walls. In nature,
biofilms constitute a protected growth modality that
allows the bacteria to survive in hostile environments.
1.3.3.2 Bacterial biofilms( 生物膜 )

44. S. epidermidis biofilm colonized on surface of venous duct

45. The characters of bacterial biofilm
※ There is a circulation system in biofilm, so bacterial
in this community can exchange nutrition and metabolic
product each other
※ Counteract the defense system of the host and toxic
effect of antibiotics
※ Transfer antibiotic resistant gene rapidly.

46. What is virulence
The ability of any agent of infection to
produce disease. The virulence of a
microorganism (such as a bacterium or virus)
is the measurement of the severity of the
capable of disease.
Invasiveness
Toxin
Virulence

47. 2. Toxin
•ExotoxinExotoxin
•EndotoxinEndotoxin

48. An exotoxin is a soluble protein excreted by a
microorganism. An exotoxin can cause damage to the
host by destroying cells or disrupting normal cellular
metabolism. most G+
and few G-
bacteria produce
exotoxins. They are highly potent and can cause major
damage to the host. Exotoxins may be secreted, or,
similar to endotoxin, may be released during lysis of
the cell.
ExotoxinExotoxin

49. Exotoxin
Origin
G + bacteria (most)
G ­ bacteria
Release
Secreted by living bacteria

50. Physical and chemical properties
• Protein
• Heat ­resistance : Sensitive

51. Thermolabile （ inactivated after treated
with 60 ～ 80 for 30 minutes).℃
Exception ： staphylococcal enterotoxin can
resist
the treatment of 100 for 30 minutes℃ ，
and it is also resist the digestion of digestive
enzymes.

52. ActiveActive BindingBinding
AA
Cell surfaceCell surface
BB
A-B toxinsA-B toxins
Structure

53. B subunit
（ Binding ）
• Determine the tissue
specificity of the toxin
• Powerful antigenicity
• can not be inactivated by
formaldehyde, while it can
be purified for subunit
vaccine.--Toxoid
A subunit
(Toxic)
• Determine the toxic
of the toxin
• weak antigenicity
• can be inactivated
by formaldehyde
A-B toxinsA-B toxins

54. Immunity
• Antitoxin
– An antibody that specifically interacts with and
neutralizes a toxin
– Application: treatment or urgent prevention
measure
• Toxoid
– An exotoxin modified so that it is no longer toxic
but is still able to induce antibody formation
– Application: vaccine

55. Toxicity
• High
• Tissue specificity
• Powerful antigenicity ： antitoxin and toxoid

56. Types
Enterotoxin
–enterotoxin (Staphylococcus aureus)
cytotoxin
– diphtheria toxin (Corynebacterium diphtheriae)
neurotoxin
– tetanospasmin (Clostridium tetanus)

57. Mechanism of C. tetaniMechanism of C. tetani
Organisms produces neurotoxin (tetanospasmin)Organisms produces neurotoxin (tetanospasmin)
Toxin travel along peripheral nerve toToxin travel along peripheral nerve to
anterior horn cells of spinal cordanterior horn cells of spinal cord
Inhibit neurotransmitter from inhibitory neuronInhibit neurotransmitter from inhibitory neuron
Continuous muscle contractionContinuous muscle contraction
TrismusTrismus or lockjaw, risus sardonicus , opisthotonos, dysphagia, dyspneaor lockjaw, risus sardonicus , opisthotonos, dysphagia, dyspnea
[d s'fe d ə]ɪ ɪ ʒɪ[d s'fe d ə]ɪ ɪ ʒɪ 咽下困难咽下困难 [d sp'ni ə]ɪ ː[d sp'ni ə]ɪ ː 呼吸困难呼吸困难 [ə 'p sθə tənə z]ʊ ɪ ʊ ʊ[ə 'p sθə tənə z]ʊ ɪ ʊ ʊ 角弓反张角弓反张
neurotoxin

58. sardonic smile (risus sardonicus)sardonic smile (risus sardonicus)
lockjawlockjaw
Rigid paralysisRigid paralysis

59. Clostridium botulinumClostridium botulinum
Botulinum toxinBotulinum toxin
- inhibits acetylcholine release- inhibits acetylcholine release
- inhibits nerve impulses- inhibits nerve impulses
-muscles inactive-muscles inactive
-flacid paralysis-flacid paralysis

60. Toxin Gene Location
Subunit
Structure
Target Cell
Receptor Biologic Effects
Anthrax
toxins
Bacillus
anthracis
Plasmid Three
separate
proteins
(EF, LF,
PA)
Unknown,
probably
glycoprotein
EF + PA: increase in target cell
cAMP level, localized edema;
LF + PA: death of target cells
and experimental animals
Bordetella
adenylate
cyclase
toxin
Bordetella
sp.
Chromosomal A-B Unknown,
probably
glycolipid
Increase in target cell cAMP
level, modified cell function or
cell death
Botulinum
toxin
Clostridium
botulinum
Phage A-B Possibly
ganglioside
(GD1b
)
Decrease in peripheral,
presynaptic acetylcholine
release, flaccid paralysis
Cholera
toxin
Vibrio
cholerae
Chromosomal A-5B Ganglioside
(GM1
)
Activation of adenylate
cyclase, increase in cAMP
level, secretory diarrhea
Diphtheria
toxin
Corynebacte
rium
diphtheriae
Phage A-B Growth
factor
receptor
precursor
Inhibition of protein synthesis,
cell death
Heat-labile
enterotoxins
Escherichia
coli
Plasmid Similar or identical to
cholera toxin
Properties of A-B Type Bacterial Toxins

61. Pertussis
toxin
Bordetella
pertussis
Chromoso
mal
A-5B Unknown,
probably
glycoprotein
Block of signal transduction
mediated by target G
proteins
Pseudomon
as exotoxin
A
Pseudomon
as
aeruginosa
Chromoso
mal
A-B Unknown, but
different from
diphtheria toxin
Similar or identical to
diphtheria toxin
Shiga toxin Shigella
dysenteriae
Chromoso
mal
A-5B Glycoprotein or
glycolipid
Inhibition of protein
synthesis, cell death
Shigalike
toxins
Shigella sp.,
E. coli
Phage Similar or identical to Shiga
toxin
Tetanus
toxin
Clostridium
tetani
Plasmid A-B Ganglioside (GT1
)
and/or GD1b
Decrease in
neurotransmitter release
from inhibitory neurons,
spastic paralysis
Toxin Organism
Gene
Location
Subunit
Structure
Target Cell
Receptor Biologic Effects
Properties of A-B Type Bacterial Toxins

62. Endotoxin
Origin G - bacteria
Release Cell wall lysis required

63. Physical and chemical properties
• LPS Lipopolysaccharide: Lipid A
• Heat -resistance : Resistance

64.  Low
 poor antigenpoor antigen , no toxoid
 Endotoxin effects:Endotoxin effects: no tissue specificity
 Fever-pyrogen 1 microgram/ kgFever-pyrogen 1 microgram/ kg
 leukocytosisleukocytosis
 hypotensionhypotension
 Shwartzman phenomenon and disseminatedShwartzman phenomenon and disseminated
intravascular coagulation (DIC).intravascular coagulation (DIC).
 Endotoxemia and shockEndotoxemia and shock
Toxicity

65. Lipid A of lipopolysaccharide
is responsible for endotoxin
activity
Pathogenesis of sepsis
(septicemia)
Endotoxin (LPS)-mediated toxicity

66. Fever,
leukopenia followed by leukocytosis,
activation of complement, thrombocytopenia,
disseminated intravasacular coagulation,
decreased peripheral circulation and perfusion to
major organs (multiple organ system failure),
Shock and death.
Peptidoglycan, teichoic and lipoteichoic acids of gram-
positive bacteria stimulate pyrogenic acute phase
responses and produce endotoxin-like toxicity
Back
Endotoxin-mediated toxicity

67. Endotoxins
 Detection of endotoxin:
The Limulus lysate test

68. Low, no toxoid
Low, no tissue
specificity
High, antitoxin, toxoid
High, tissue specificity
Immunity
Toxicity
ResistanceHeat-resistance Sensitive
LPSProteincomposition
Secreted from living cells or Released upon
released upon bacterial lysis bacterial lysis
Release
Endotoxin
G -
Exotoxin
G + and G -
Properties
Origin
The difference between exotoxin
and endotoxin

69. Virulence
invasiveness
Virulence
Adherence factor
exotoxin
toxin
endotoxin
Capsule and slime layer
Invasive enzyme

70. Virulence of pathogenic bacterial

71. InfectionInfection determinantdeterminant interactioninteraction Infection typeInfection type
immunity >Virulence
immunity <Virulence
immunity ≈Virulence
Inapparent
infection
Apparent
infection
latent
infection
environment
Host immunity
Pathogenicity
(Virulence,
number , Portal)

72. Exercises
• Definitions: normal flora, opportunistic pathogen,
exotoxin, endotoxin, antitoxin, toxoid,
bacteremia, septicemia, toxemia,
endotoxemia, carrier
1.The medical significance of normal flora
2.The conditions causing opportunistic infections
3.Virulence of bacteria