Baedah Madjid

Depart. of Microbiology,
Medical Faculty, Hasanuddin University.
2007

Student must able to explain about the

patho-mechanisms of infection
Student must know how to explain about:
the role of the bacterial normal flora
the stages of the bacterial pathogenesis
the microbial factors involved in the

onset and spread of the microbial infection.

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

 Definition : terms connected

The Role of the Normal flora in Diseases
Transmission of the Infection
The Stages of bacterial pathogenesis
Factors affect the outcomes of the infection
Summary

 Normal Flora: microorganisms that are frequently

found in the various body sites in normal, healthy individuals.

Pathogens :
- in medicine: the pathogen is any microorganisms capable
of causing diseases

- microbiology: being pathogen microbe must posses

virulence factors (microbial pathogenicity)

Pathogen opportunistic
The non-pathogen bacteria pathogen on susceptible host

 Pathogenesis = pathogeny:
the organization & development of the infection

Pathogenicity: the quality or state or being pathogenic;

degree of pathogenic capacity.

Invasion: the penetration of the hosts body by

microorganisms

Normal Flora: microorganisms that

are frequently
found in various body sites in
normal, healthy
Origin
individuals.
of human NF: environment :
other human
skin & mucous, water, air
One organism will always
predominate in one
anatomical site. This balance
between microbes
The
and
the host tends
benumbers
stable. of
constituents
andto
the
the flora vary in
different areas and sometime at
different ages &

 Mostly bacteria, & some fungi

- Non pathogen
- Pathogen

Carrier state

Bacterial normal flora :

- Resident NF: strain that have an establish niche at
one of the body sites

-Transient NF:
acquired from the environment
establish themselves briefly
excluded by:
competition
hosts innate or immune defense mechanisms.

Ecology is a science concerned with

the inter- relationship of organisms
and their environment.
The environment of an organism is
the product of the presence and
activities of other organisms that
inhibit it is of nonliving chemical and
physical forces.
That product are from :
- other microorganisms
- the host
The organisms tend to segregate and
to becoe adapted to a particular
habitat or environment niche.

Host - NF relationship symbiotic

:
living animals/human use as
habitats by other organisms can
be
grouped as: : one species use the
Commensalisms
body of
other larger species

Mutualism: provide reciprocal benefits

for the
two organisms involved.

Parasitism : benefits only the

parasite.

 Flora that reach sterile sites

may cause
disease:

- E. coli urinary bladder UTI

- Perforation of the colon from
rupture a
diverticulum or a penetrating
abdominal wound
Mouth
feces
into may
peritonium
flora
reach
heart
peritonitis
valves by caused
primarily by facultative members
transient
bacteremia colonized
of the
flora.
a previously
Mouth
flora
plays
mayor
role
damaged heart valve.

in dental carries.

Compromised immune system opportunity

for invasion opportunistic pathogen

Non-specific toxic effects of colonic flora are

postulated

Blind-loop overgrowth may cause fat malabsorption and B12 deficiency.

Colonization of jejenum occur in sprue.

Ammonia production and bypass lead to

hepatic encephalopathy.

Priming of Immune system

Sterile animal has little immunity to infection

Exclusionary effect
- Lactobacilus vaginal flora protect host
against transmitted N. gonorrhea
- Exclusionary effect makes entrance of
pathogens more difficult

Production of Essential Nutrients

-Help food digestion
- Produce some vitamins

1. Contamination port the entry:

epithelium cell
2. Attachment to host cells = adherence
3. Invasion = Penetration
4. Multiplication
5. Dissemination
6. Elimination

Progression
Resolution

Transmission
Skin & Mucous
Site of Microbial Contamination
or

Port the Entry

 Exogenously
Human to human:
direct contact
- Non-direct contact
- Blood-borne
- Vertical
-

Nonhuman to human

 Human to human:
-Direct contact
: Gonorrhea
- Non-direct contact : Dysentry
- Blood-borne
: Syphilis
- Vertical (mother to her baby):
Transplacental
At time of birth
Breast milk

: Triponema pallidum
Cytomegalovirus
: Chlamydia trachomatis
Neisseria gonorrhoe
: Staphyloococcus aureus

 Nonhuman to human
Soil source

: Tetanus

Water source : Legionnaires disesase

Animal source :
Directly

: Cat-scratch fever

Via insect vector : epidemic typhus

Via animal excreta :
- Lisa (dogs saliva)
- Leptospirosis (rats urine)

1. Contamination port the entry:

epithelium 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. Contamination
2. Attachment to host cells

3. Invasion

Multiply

Colonization
Carrier state
(pathogen)

1. Contamination port the entry:

epithelium cell
2. Attachment to host cells
3. Invasion = Penetration

The penetration of the body of a host by

a microorganism (Merriam Websters Medical
Desk Dictionary)

 Getting into

cells multiplication

The advantages for intracellular (epithelia or PMN cells)

pathogens :
. Environment potentially rich in nutrients
. No competing microorganisme

Resisting the degradative enzymes

Bacteria & viruses inter the cell
reorganization of cytoskeleton microbes in a
membrane-bound vesicle in an acidic
environment.
Bacteria
can resist the degradative enzymes by:
. elaborate enzymes dissolves the surrounding
membranes
replicate in within relative cyroplasm.
. tolerate to initial endosome-lysosome fusion, or
. inhibit the acidification of the endosomal vesicle inhibit

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. Contamination port the 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

NO.

V. FACTORS

USED FOR

1.
2.

Protein pilli
Attachment
Polysaccharide/Polypeptide Avoiding ingestion
capsule

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

Comparison of Properties
Sources

Certain sp of Gram-pos &

Gram-negative

Cell wall of Gramnegative

Secreted from
cell

Yes

No

Chemistry

Polypeptide

Lipopolysaccharide

Location of gene

Plasmid or bacteriophage

Bacterial chromosome

Toxicity

High

Low

Clinical Effect

Various effects

Fever shock

Mode of action

Various mode

Includes TNF &

Interleukin-1

Antigenicity

Induce high titer Ab:

antitoxin

Poorly antigenic

Vaccine

Toxoids

No toxoid or vaccines
avaiable

Heat stability

Destroyed rapidly at 60oC

(except Staphyl enterotoxin)

Stable at 100oC for 1 hr

Typical diseases

Tetanus, botulisms,

Meningococcemia, sepsis

Mode of Action of Exotoxin

1. As superantigen : Staph. aureus (enterotoxin &
TSST), Clost. perfringens, Bacillus cereus, Strept. pyogenes
(erythrogenic toxin)

2. Inactivates GTPases in enterocytes: Clost. difficile

3. Stimulates adenylate cyclase : Vibrio cholerae,
toxigenic E. coli, Bordetella pertussis
4. Inactivates protein synthesis: E. coli O157, C.
diphtheriae
5. Inhibits glycine release: Clost. tetani

Mode of Action of Exotoxins

6. Inhibits acetylcholine release: Clost. botulinum
7. Inhibits chemokine receptor: Bordetella pertussis
8. Protease cleaves desmosome in skin: Staph. aureus
(scalded skin syndrome)
9. Lecithinase cleaves cell membranes: Clost.
perfringens
10. An adenylate cylase: edema factor of Bacilus
anthracis
11. A protease: lethal factor of Bacilus anthracis

The Biologic Effects of Endotoxins

1. Fever : release of endogenous pyrogen (interleukin-1) from
macrophages

2. Hypotension, shock and impaired perfusion of essential

organ: bradykinin-induced vasodilatator membrane permeability
& peripheral resistance

3. Disseminated intravascular coagulation: activation of the

coagulation system thrombosis, petechial or purpuric rash and tissue
ischemia vital organ failure .

4. Activation of the alternative pathway of the complement:

inflammation and tissue damage

5. Activation of macrophages: phagocytic ability , Ab production

(ctivation of many clones of B lymphocytes)

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

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 defences.

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. Normal Flora
2. Transmission of Bacteria
3. Pathogen:
- Posses virulence factors
- Opportunistic pathogen:
NF or colonization of pathogens on carrier
Environment bacteria

4. 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, McGrawHill, Singapore, 2004.
Cohen, J. et al. Infectious Diseases, 2nd Edition, Mosby, Sydney, 2004.
Inglis, T.J.J. Microbiology and Infection, a clinical core text for
integrated curricula with self-assessment, Churchill-Livingstone,
Sydney, 2003.
Levinson, W. Review of Medical Microbiology and Immunology, 9th
Edition, McGraw Hill-Lange, Singapore, 2006.
Joklik, WK., Willett, HP., Amos, DB., Wifert, CM. Zinsser
Microbiology, 20th edition, Appleton & Lange, Connecticut, 1992.
Mims, C., et al. Medical Microbiology, 3rd Edition, Mosby, Sydney,
2004.
Nath, S.K., Revankar, S.G. Problem Base Microbiology, SaundersElsevier, Philadelphia, 2006.
Ryan, KJ., Ray, CG. Sherris Medical Microbiology, an Introduction to
Infectious Diseases, McGraw-Hill, Singapore, 2004.
Strohl, W.A., Rouse, H., Fisher, B.D. Lippincotts Illustrated Reviews
Microbiology, Lippincott Wlliams & Wilkins, Maryland, 2001.
Virella G. Microbiology and Infectious Diseases, 3rd Edition, Edited.,
Williams and Wilkins, Baltimore, 1997.