To be able to explain about pathomechanisms of infection

To know how to explain about:

the steps of bacterial pathogenesis
the microbial factors involved in the

onset and spread of microbial infection.

the strategy for bacterial survival
the factors affect the outcome of infection

 Definition : terms connected

Transmission Infection

Steps of bacterial pathogenesis

Factors affect the outcomes of infection

Summary

 Normal Flora: microorganisms that are frequently

found in various body sites in normal, healthy individuals.

Pathogens :

- in medicine: pathogen is any microorganisms capable of

causing diseases

- Microbiology: being pathogen microbe must posses

virulence factors (microbial pathogenicity)

Pathogen opportunistic
Non-pathogen bacteria pathogen on susceptible host

 Pathogenesis = pathogeny:
the organization & development of infection

Pathogenicity: the quality or state or being pathogenic;

degree of pathogenic capacity.

Invasion: the penetration of the hosts body by

microorganisms

General Concepts

Host Susceptibility
Resistance to bacterial infections is
enhanced by phagocytic cells and an
intact immune system. Initial resistance
is due to nonspecific mechanisms.
Specific immunity develops over time.
Susceptibility to some infections is
higher in the very young and the very
old and in immunosuppressed patients.

antibody response to Salmonella typhi during typhoid fever

relationship to septicemia.

Bacterial Infectivity
Bacterial infectivity results from a
disturbance in the balance between
bacterial virulence and host
resistance. The "objective" of
bacteria is to multiply rather than to
cause disease; it is in the best
interest of the bacteria not to kill the
host.

Host Resistance
Numerous physical and chemical attributes of the
host protect against bacterial infection. These
defenses include the antibacterial factors in
secretions covering mucosal surfaces and rapid rate
of replacement of skin and mucosal epithelial cells.
Bacteria invading tissues encounter phagocytic cells
that recognize them as foreign, and through a
complex signaling mechanism involving interleukins,
eicosanoids, and complement, mediate an
inflammatory response in which many lymphoid cells
participate.

Genetic and Molecular Basis for

Virulence
Bacterial virulence factors may be
encoded on chromosomal, plasmid,
transposon, or temperate
bacteriophage DNA; virulence factor
genes on transposons or temperate
bacteriophage DNA may integrate
into the bacterial chromosome.

Host-Mediated Pathogenesis
In certain infections (e.g.,
tuberculosis), tissue damage results
from the toxic mediators released by
lymphoid cells rather than from
bacterial toxins.

eralized mechanisms of bacterial pathogenesis: bacteria-ind

toxicity or host-mediated damage.

Intracellular Growth
Some bacteria (e.g., Rickettsia
species) can grow only within
eukaryotic cells, whereas others
(e.g., Salmonella species) invade
cells but do not require them for
growth.

les of pathogenic bacteria, indicating their preferred growth

within the host. (ETEC:enterotoxigenic E coli)

Virulence Factors
Virulence factors help bacteria to (1)
invade the host, (2) cause disease,
and (3) evade host defenses.

The following are types of

virulence factors:

Adherence Factors: Many pathogenic bacteria

colonize mucosal sites by using pili (fimbriae) to
adhere to cells.
Invasion Factors: Surface components that allow
the bacterium to invade host cells can be
encoded on plasmids, but more often are on the
chromosome.
Capsules: Many bacteria are surrounded by
capsules that protect them from opsonization and
phagocytosis.

Endotoxins: The lipopolysaccharide endotoxins on

Gram-negative bacteria cause fever, changes in
blood pressure, inflammation, lethal shock, and
many other toxic events.
Exotoxins: Exotoxins include several types of
protein toxins and enzymes produced and/or
secreted from pathogenic bacteria. Major categories
include cytotoxins, neurotoxins, and enterotoxins.
Siderophores: Siderophores are iron-binding factors
that allow some bacteria to compete with the host
for iron, which is bound to hemoglobin, transferrin,
and lactoferrin

1. Encounter port the entry: epithel cell

2. Attachment to host cells = adherence
3. Invasion
4. Multiplication
5. Dissemination

1. Encounter port the entry: epithel cell

Site of Microbial Contamination

or

Port the Entry

1. Encounter port the entry: epithel cell

2. Attachment to host cells = adherence

Pili = fimbriae

Bacteria :
adhesin

Host epithel:
receptor

Non- fibrillae

- Pilli or fibrillae

- Afibrial adhesins
* Lectin (carbohydrate-binding-protein)

* Lipoteichoic acid
* Fibronectin-binding-protein
* M-protein
* Outer membrane protein
* Polysaccharide capsule

1. Encounter
2. Attachment to host cells

3. Invasion

Multiply

Colonization
Carrier state
(pathogen)

1. Encounter port the entry: epithel cell

2. Attachment to host cells
3. Invasion

The penetration of the body of a host by

a microorganism (Merriam Websters Medical
Desk Dictionary)

 Getting into cells multiplication

Resisting the degradative enzymes
The advantages for intracellular (epithelia or
PMN cells) pathogens :
. Environment potentially rich in nutrients
. No competing microorganisms
. No immune system

Mechanisms
Survival the phagocyte &
Complement attack
Inhibition of chemotaxis
Killing by phagocyte before
ingestion
Avoiding ingestion (Phagocytose)

Examples
C5a peptidase by Str. pyogenes
-toxin and leukocidin by Staph.
aureus
Bacterial capsule (Streptococcus

pneumoniae.)
LPS O Ag in Gr-neg rods
Coating with IgA Antibodies
(Neisseria meningitidis)
M. protein (Streptococcus
pyogenes)

Mechanisms

Examples
Inhibition of phagosome fusion
(Chlamydia trachomatis)
Escape phagolysosome
(Listeria monocytogenes)
Resistance to lysosomal product
(Salmonella typhimurium)
Inhibition of early host gene
expression (M. tuberculose)

Surviving within phagocytes

Antigenic variation
Tolerance

Shift and drift in influenza A virus

Immunosuppression
-Destroying lymphocytes
- Proteolysis of antibodies
Presence in inaccessible sites

Prenatal infections
Depletion of CD4+ T cells by HIV
IgA protease by H. influenzae
Latent infection in dorsal root
ganglia (Herpes simplex virus)

1. Encounter entry
2. Attachment to host cells
3. Invasion
4. Multiplication

Metabolite excretion
Tissue Damage

Primary lesion

MECHANISMS OF CELL AND TISSUE

DAMAGE BY MICROORGANISMS
Mechanism
Direct damage
by
microorganisms

Production of toxins

Examples
See next table

Production of enzymes Proteases, coagulase,

DNAse,
Apoptosis
Virus induced
cytopathic effects:
cell lysis
formation of
syncytium
Inclusion bodies:
- intracytoplasmic
- Nuclear
Transformation

HIV (CD4+ T cells),

Shigella flexneri
(macrophage)

Cytomegalovirus
Respiratory syncytial
virus
Rabies
Herpes viruses
Human papilloma-viruses
type 16

MECHANISMS OF CELL AND TISSUE

DAMAGE BY MICROORGANISMS
Mechanism

Examples

Damage via Cytotoxic T cells & Production of measles

natural killer
rash
the host
lymphocytes
immune
Autoimmunity
Acute Rheumatic fever
response
Immediate hypersensitivity

Rashes associated with

helminthic infection

Cytotoxic hypersensitivity

Cell necrosis induced by

hepatitis B

Immune complexes Glomerulonephritis in

malaria
Delayed type
hypersensitivity

Tuberculosis granuloma

EXAMPLES OF BACTERIAL TOXINS

Toxin type

Sources

Toxin

Endotoxin
(LPS, lipid
A)

Gr- Bacteria

Endotoxin

Macrophage,
Neutrophils,
lymphocytes,
Plasma
components

Septic shock

Membrane
disrupting
toxins

Staph. aureus

-toxin

Many cells
types

Tissue necrosis

L.monocytoges

Listeriolysin

Many cells
types

Escape from the

phagosome

Cl. perfringens Perfringolysin-O

Many cells
types

Gas gangrene

Cl. tetani

Tetanospasmin

Synaptic
transmission

Spastic paralysis

C. diphtheriae

Diphtheria
toxin

Many cells
types

Paralysis

Vibrio cholerae Cholera toxin

Intestinal
cells

Profuse watery
diarrhea

Str. pyogenes

T. cells,
macrophage

Fever, eruption,
toxic-shock like

A-B type
toxins

Superantigen

Streptococcal
pyogenic

Target

Effects

NO.

V. FACTORS

USED FOR

1.
2.

Pilli
Capsule

Attachment
Avoiding ingestion

3.
4.

Protein M
Outer membrane protein

Attachment
Attachment

5.
6.

Toxin
Hyaluronidase

See Toxin tables

Spreading

7.
8.

IgA protease
DNAse

Breaking Surface IgA

Destroying hosts cell

9.

Coagulase

Avoiding ingestion

 Endotoxin
- = Lypopolysacchride (LPS) wall of

negative-gram bacteria
- Septic shock

Exotoxin
- Metabolite excretion protein
- Effect: Lyses
Neurotoxin
Enterotoxin

1. Encounter entry
2. Attachment to host cells
3. Invasion
4. Multiplication
5. Dissemination

Directly

Indirectly
-hematogenously
--lymphatogenously

Bacteria can be eliminated by:

1. Natural host defense:
- Lysozyme and other enzyemes
- Acid
- Complement

2. Acquired host defense:

- Antibodies

3. Antibiotics therapy

Symptomatic
Asymptomatic disease
= sub-clinic diseases
Depend on:
1. The organisms ability to breach host barrier & to
evade destruction by innate local and tissue host defenses.

2. The organisms biochemical tactics to replicate, to spread, to

establish infection, and to cause disease.

3. The microbes ability to transmit to a new susceptible host.

4. The hosts innate and adaptive immunologic ability to control
and eliminate the invading microbes.

DOSE OF MICROORGANISMS REQUIRED TO

PRODUCE INFECTION IN HUMAN VOLUNTERS
MICROBE

ROUTE

DISEASE-PRODUCING DOSE

Rhinovirus

Pharynx

200

Salmonella typhi

Oral

105

Shigella spp.

Oral

10 - 1000

Vibrio cholerae

Oral

108

Mycobacterium
tuberculosis

Inhalation

1 - 10

1. Pathogen:
- Posses virulence factors
- Opportunistic pathogen:
NF or colonization of pathogens on carrier
Environment bacteria

2. Outcomes of infection is depend on:

- Pathogenicity of bacteria
- Dose of contamination
- Host defense mechanisms

FURTHER READING

Brooks, GF., Butel, JS., Morse, SA. Jawetz, melnick, &

Adelbergs Medical Microbiology. 23rd Edition, International
Edition, McGraw-Hill, Singapore, 2004.
Cohen, J. et al. Infectious Diseases, 2nd Edition, Mosby,
Sydney, 2004.
Joklik, WK., Willett, HP., Amos, DB., Wifert, CM. Zinsser
Microbiology, 20th edition, Appleton & Lange,
Connecticut1992.
Mims, C., et al. Medical Microbiology, 3rd Edition, Mosby,
Sydney, 2004
Ryan, KJ., Ray, CG. Sherris Medical Microbiology , an
Introduction to Infectious Diseases, McGraw-Hill,
Singapore, 2004.
Virella G. Microbiology and Infectious Diseases, 3rd Edition,
Edited., Williams and Wilkins, Baltimore, 1997.