Baedah Madjid

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

Student must able to explain about the pathomechanisms 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
individuals.

Origin of human NF: environment : other human

skin & mucous, water, air

One organism will always predominate in one

anatomical site. This balance between microbes
and the host tends to be stable.
The

constituents and the numbers of the flora vary in

different areas and sometime at different ages &
physiologic states

 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 interrelationship 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:

Commensalisms : one species use the 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
feces into peritonium peritonitis caused
primarily by facultative members of the flora.

Mouth flora may reach heart valves by

transient bacteremia colonized a previously
damaged heart valve.

Mouth flora plays mayor role 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
: Triponema pallidum
Cytomegalovirus
At time of birth
: Chlamydia trachomatis
Neisseria gonorrhoe
Breast milk
: Staphyloococcus aureus
Cytomeglovirus

 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)
Fomite source : Staphylococcal skin infection

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
lysosomal fusion.

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

Shift and drift in influenza A virus

Tolerance
Immunosuppression
-Destroying lymphocytes
- Proteolysis of antibodies

Prenatal infections

Presence in inaccessible sites

Latent infection in dorsal root

ganglia (Herpes simplex virus)

Depletion of CD4+ T cells by HIV

IgA protease by H. influenzae

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

Examples

Production of toxins
See next table
Production of enzymes Proteases, coagulase,
DNAse,
+ T cells),
HIV
(CD4
Apoptosis
Shigella flexneri
(macrophage)
Virus induced
cytopathic effects:
cell lysis
Cytomegalovirus
formation of
Respiratory syncytial
syncytium
virus
Inclusion bodies:
- intracytoplasmic
Rabies
- Nuclear
Herpes viruses

Transformation

Human papilloma-viruses
type 16

MECHANISMS OF CELL AND TISSUE

DAMAGE BY MICROORGANISMS
Mechanism
Damage via
the host
immune
response

Examples

Cytotoxic T cells & Production of measles

natural killer
rash
lymphocytes
Autoimmunity
Acute Rheumatic fever
Immediate hypersensitivity
Cytotoxic hypersensitivity
Immune complexes
Delayed type
hypersensitivity

Rashes associated with

helminthic infection
Cell necrosis induced by
hepatitis B
Glomerulonephritis in
malaria
Tuberculosis granuloma

NO.

V. FACTORS

1.
2.

Protein pilli
Polysaccharide/Polypeptide
capsule
Protein M
Outer membrane protein
Toxin
Hyaluronidase
IgA protease
DNAse
Coagulase

3.
4.
5.
6.
7.
8.
9.

USED FOR
Attachment
Avoiding ingestion
Attachment
Attachment
See Toxin tables
Spreading
Breaking Surface IgA
Destroying hosts cell
Avoiding ingestion

Comparison of Properties
Sources

Certain sp of Gram-pos &

Gram-negative
Yes

Cell wall of Gramnegative

No

Polypeptide

Lipopolysaccharide

Location of gene

Plasmid or bacteriophage

Bacterial chromosome

Toxicity

High

Low

Clinical Effect

Various effects

Fever shock

Mode of action

Various mode

Antigenicity

Induce high titer Ab:

antitoxin
Toxoids

Includes TNF &

Interleukin-1
Poorly antigenic

Secreted from
cell
Chemistry

Vaccine
Heat stability
Typical diseases

No toxoid or vaccines
avaiable
Stable at 100oC for 1 hr

Destroyed rapidly at 60oC

(except Staphyl enterotoxin)
Tetanus, botulisms, diphtheria Meningococcemia, sepsis
by Gram-negative rods

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
Endotoxin Gr- Bacteria
(LPS, lipid
A)
Membrane
disrupting
toxins

A-B type
toxins

Superantigen

Toxin
Endotoxin

Staph. aureus

-toxin

L.monocytoges

Listeriolysin

Cl. perfringens Perfringolysin-O

Cl. tetani
Tetanospasmin
C. diphtheriae Diphtheria
toxin
Vibrio cholerae Cholera toxin
Str. pyogenes

Staph. aureus

Streptococcal
pyogenic
exotoxin
Toxic shock
toxin

Target
Macrophage,
Neutrophils,
lymphocytes,
Plasma
components
Many cells
types
Many cells
types
Many cells
types
Synaptic
transmission
Many cells
types
Intestinal
cells
T. cells,
macrophage

T. cells,
macrophage

Effects
Septic shock

Tissue necrosis
Escape from the
phagosome
Gas gangrene
Spastic paralysis
Paralysis
Profuse watery
diarrhea
Fever, eruption,
toxic-shock like
syndrome
Toxic shock
syndrome

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

Indirectly
-hematogenously
--lymphatogenously

Directly

Bacteria can be eliminated by:

1. Natural host defense:
- Lysozyme and other enzyemes

- Acid
- Complement

2. Acquired host defense:

- Antibodies

3. Antibiotics therapy

Symptomatic disease
Asymptomatic = 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.