Bacterial Infection and

Pathogenesis
•  pathogenesis(how a disease develops)
• pathogenicity (disease­causing ability of
microorganisms)
• virulence (degree of pathogenicity)
 Section 1 Normal flora 

Microorganisms that 
live on or in human 
bodies, and ordinarily 
do not cause human 
diseases
  The medical significance of 
normal flora
•  Antagonism 
– Mechanisms 
•  Competition for receptors on host cells 
•  Competition for nutrients 
•  Metabolic or toxic products 
•  Nutritional function 
•  Immunity 
 Opportunistic pathogen

normal flora  that, under ordinary 
circumstances, cause no harm but can 
cause disease under certain conditions 
 Under what conditions will opportunistic
pathogens cause human diseases?

•  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
Section 2 Bacterial infection

Cause disease
细菌

toxins
bacteria
bacteria
bacteria 细菌
细菌
bacteria
bacteria

outerbody inbody
Immune status
of the host
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 Antibody-mediated
acquired immunity
cell-mediated
 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.
 Pathogenicity of bacteria

 pathogenicity （ decide by):

 virulence factors of the bacterium
 the number of infecting bacteria
 route of entry into the body
 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.
 Portals of entry

 skin
 respiratory system
 ingestion system
 genitourinary system

C. tetani
 The size of the inoculum

 The quantity of microbes in the inoculating dose.

 The originate and progress of infection

 A.The source of the infection

 B.routes of pathogen transmission

 C.Patterns of infection
 A.The source of infection

 Living reservoirs
Persons or animals with frank symptomatic
infection are obvious sources of infection
 Nonliving reservoirs
 Sources of infectious diseases
 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 
 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
 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
 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
 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
 C. Patterns of infection
acute infection
Apparent infection
chronic 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
 Inapparent infection: also called
subclinical infection that has no
detectable clinical symptoms
 local infection
generalized/systemic infection

Localized infection stands for the case that the

microbe enters the body and remains confined to a
specific tissue
 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.
 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
 Local lesion

局局

toxin
毒 部部
病病
素 灶灶
Defense function↓↓

血液 toxin 毒素
toxin

special toxic pathogenic bacterium Organism is

can grow in blood
symptom seriously damaged,
toxic symptom all over
the body 。

Bacteremia
Toxemia
Septicemia
e.g.tetanus
 局局
毒

toxin
部部
病病
素 灶灶

blood 毒素
toxin

When Pyosis bacteria

cause Septicemia ，
New pyosis focus of multiple pyosis focus
of infection will
infection happen.e.g.
Pyosepticemia staphylococci aureus
Section 3. Bacterial pathogenicity
Pathogen
A microorganism that causes disease 
What factors determine 
bacterial pathogenicity?
•  Virulence 
•  The amount of entry 
•  The portal of entry 
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
Virulence
Toxin
1. Invasiveness

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

•  Adherence factor 
– Pilus 
– LTA 
•  Capsule  
•  Invasive enzyme
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
1.2 Adherent mechanisms

Electrostatic attraction( 静电 吸引 )
Hydrophobic interaction ( 疏水作用 ) Nonspecific adherence
Cationic bridge( 阳离 子桥联 ) (Reversible)

ligand-receptor( 配体 - 受体 )bonding Specific adherence

(Irreversible )
 Examples of Bacterial Adherence Mechanisms
Microbe Adhesin Receptor
S. Aureus LTA Unknown

S. epidermidis Slime Unknown

Streptococcus, group A LTA-M protein Fibronectin
complex
S. pneumoniae Surface protein N-acetylhexosamine-gal
E. coli Type 1 fimbriae d-Mannose
  Colonization factor GM1 ganglioside
antigen fimbriae
  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 tissue tropism for bacterial infection
Bacteria Tissue
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
 Tissue tropism

Different bacteria adhere to different

host cell by different ligand
1.3 Invasive mechanisms
1.3.1 Capsule and microcapsule
1.3.2 Invasive Enzyme( 侵袭 性酶类 )
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.
Microcolony( 微菌落 )
 1.3.3.2 Bacterial biofilms( 生物膜 )
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.
S. epidermidis biofilm colonized on surface of venous duct
 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.
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
Virulence
Toxin
2. Toxin

•Exotoxin

•Endotoxin
 Exotoxin
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.
 Exotoxin
Origin
G + bacteria (most)
G ­ bacteria

Release
Secreted by living bacteria
Physical and chemical properties

• Protein
• Heat ­resistance : Sensitive
 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.
Structure
A-B toxins

Cell surface

Active Binding

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

• High
• Tissue specificity
• Powerful antigenicity ： antitoxin and toxoid
Types
Enterotoxin
–enterotoxin (Staphylococcus aureus)
cytotoxin
– diphtheria toxin (Corynebacterium  diphtheriae)
neurotoxin
– tetanospasmin (Clostridium tetanus)
neurotoxin

Mechanism of C. tetani
Organisms produces neurotoxin (tetanospasmin)

Toxin travel along peripheral nerve to

anterior horn cells of spinal cord

Inhibit neurotransmitter from inhibitory neuron

Continuous muscle contraction

Trismus or lockjaw, risus sardonicus , opisthotonos, dysphagia, dyspnea

[dɪs'feɪdʒɪə] 咽下困难 [dɪsp'niːə] 呼吸困难 [əʊ'pɪsθəʊtənəʊz] 角弓反张
 sardonic smile (risus sardonicus)

lockjaw

Rigid paralysis
 Clostridium botulinum
Botulinum toxin
- inhibits acetylcholine release
- inhibits nerve impulses
-muscles inactive
-flacid paralysis
 Properties of A-B Type Bacterial Toxins
Subunit Target Cell
Toxin Gene Location Structure Receptor Biologic Effects

Anthrax Bacillus Plasmid Three Unknown, EF + PA: increase in target cell

toxins anthracis separate probably cAMP level, localized edema;
proteins glycoprotein LF + PA: death of target cells
(EF, LF, and experimental animals
PA)

Bordetella Bordetella Chromosomal A-B Unknown, Increase in target cell cAMP

adenylate sp. probably level, modified cell function or
cyclase glycolipid cell death
toxin
Botulinum Clostridium Phage A-B Possibly Decrease in peripheral,
toxin botulinum ganglioside presynaptic acetylcholine
(GD1b) release, flaccid paralysis

Cholera Vibrio Chromosomal A-5B Ganglioside Activation of adenylate

toxin cholerae (GM1) cyclase, increase in cAMP
level, secretory diarrhea
Diphtheria Corynebacte Phage A-B Growth Inhibition of protein synthesis,
toxin rium factor cell death
diphtheriae receptor
precursor
Heat-labile Escherichia Plasmid Similar or identical to
enterotoxins coli cholera toxin
 Properties of A-B Type Bacterial Toxins

Gene Subunit Target Cell

Toxin Organism Location Structure Receptor Biologic Effects

Pertussis Bordetella Chromoso A-5B Unknown, Block of signal transduction

toxin pertussis mal probably mediated by target G
glycoprotein proteins
Pseudomon Pseudomon Chromoso A-B Unknown, but Similar or identical to
as exotoxin as mal different from diphtheria toxin
A aeruginosa diphtheria toxin
Shiga toxin Shigella Chromoso A-5B Glycoprotein or Inhibition of protein
dysenteriae mal glycolipid synthesis, cell death
Shigalike Shigella sp., Phage Similar or identical to Shiga
toxins E. coli toxin
Tetanus Clostridium Plasmid A-B Ganglioside (GT1) Decrease in
toxin tetani and/or GD1b neurotransmitter release
from inhibitory neurons,
spastic paralysis
 Endotoxin
Origin G - bacteria
Release Cell wall lysis required
 Physical and chemical properties
• LPS Lipopolysaccharide: Lipid A
• Heat -resistance : Resistance
 Toxicity

 Low
 poor antigen , no toxoid
 Endotoxin effects: no tissue specificity
 Fever-pyrogen 1 microgram/ kg
 leukocytosis
 hypotension
 Shwartzman phenomenon and disseminated
intravascular coagulation (DIC).
 Endotoxemia and shock
 Endotoxin (LPS)-mediated toxicity

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

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
 Endotoxins

 Detection of endotoxin:
The Limulus lysate test
 The difference between exotoxin
and endotoxin
Properties Exotoxin Endotoxin
Origin G + and G - G-

Secreted from living cells or Released upon

Release
released upon bacterial lysis bacterial lysis

composition Protein LPS

Heat-resistance Sensitive Resistance

Immunity High, antitoxin, toxoid Low, no toxoid

Low, no tissue
Toxicity High, tissue specificity
specificity
 Virulence

Adherence factor
invasiveness
Capsule and slime layer
Invasive enzyme
Virulence
exotoxin
toxin
endotoxin
Virulence of pathogenic bacterial
Infection determinant interaction Infection type

Pathogenicity immunity >Virulence Inapparent

(Virulence, infection
number , Portal)

Host immunity immunity <Virulence Apparent

infection

environment immunity ≈ Virulence latent

infection
 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