Baedah Madjid

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

Student must able to explain about the patho-
mechanisms of infection
the factors affect the outcome of the
infection

Student must know how to explain about:
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 role of the bacterial normal flora




Definition : terms connected
Transmission of the Infection
The Stages of bacterial pathogenesis
Factors affect the outcomes of the infection
Summary
The Role of the Normal flora in Diseases
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
Invasion: the penetration of the hosts body by
microorganisms
Pathogenicity: the quality or state or being pathogenic;
degree of pathogenic capacity.
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
The constituents and the numbers of the flora vary in
different areas and sometime at different ages &
physiologic states
One organism will always predominate in one
anatomical site. This balance between microbes
and the host tends to be stable.
Mostly bacteria, & some fungi
- Non pathogen
- Pathogen Carrier state
Bacterial normal flora :
- Resident NF:
-Transient NF:
acquired from the environment
establish themselves briefly
excluded by:
competition
hosts innate or immune defense mechanisms.
strain that have an establish niche at
one of the body sites
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.
The organisms tend to segregate and to becoe
adapted to a particular habitat or environment
niche.
That product are from :
- other microorganisms
- the host
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.
Mouth flora plays mayor role in dental
carries.

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.
Ammonia production and bypass lead to
hepatic encephalopathy.
Compromised immune system opportunity
for invasion opportunistic pathogen
Non-specific toxic effects of colonic flora are
postulated
Blind-loop overgrowth may cause fat mal-
absorption and B12 deficiency.
Colonization of jejenum occur in sprue.
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
Site of Microbial Contamination
Port the Entry
or
Skin & Mucous
Transmission
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
receptor

Bacteria :
adhesin
Host epithel:
Pili = fimbriae 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
Colonization
Multiply
Carrier state
(pathogen)
3. Invasion
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)
. Environment potentially rich in nutrients
. No competing microorganisme
Getting into cells multiplication
Resisting the degradative enzymes
The advantages for intracellular (epithelia or PMN cells)
pathogens :
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.
Bacteria & viruses inter the cell reorganization of
cytoskeleton microbes in a membrane-bound vesicle in
an acidic environment.
Mechanisms Examples
Survival the phagocyte &
Complement attack
Inhibition of chemotaxis
Killing by phagocyte before
ingestion


C5a peptidase by Str. pyogenes
-toxin and leukocidin by Staph.
aureus
Avoiding ingestion (Phagocytose)
Bacterial capsule (Streptococcus
pneumoniae.)
LPS O Ag in Gr-neg rods
Coating with IgA Antibodies
(Neisseria meningitidis)
M. protein (Streptococcus
pyogenes)

Mechanisms Examples
Surviving within phagocytes
Inhibition of phagosome fusion
(Chlamydia trachomatis)
Escape phagolysosome
(Listeria monocytogenes)
Resistance to lysosomal product
(Salmonella typhimurium)
Inhibition of early host gene
expression (M. tuberculose)
Antigenic variation
Shift and drift in influenza A virus
Tolerance
Prenatal infections
Immunosuppression
-Destroying lymphocytes
- Proteolysis of antibodies

Depletion of CD4
+
T cells by HIV
IgA protease by H. influenzae
Presence in inaccessible sites
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 Examples
Direct damage
by
microorganisms
Production of toxins See next table
Production of enzymes Proteases, coagulase,
DNAse,
Apoptosis
HIV (CD4
+
T cells),
Shigella flexneri
(macrophage)
Virus induced
cytopathic effects:
cell lysis
formation of
syncytium
Inclusion bodies:
- intracytoplasmic
- Nuclear


Cytomegalovirus
Respiratory syncytial
virus

Rabies
Herpes viruses
Transformation Human papilloma-viruses
type 16
MECHANISMS OF CELL AND TISSUE
DAMAGE BY MICROORGANISMS
Mechanism Examples
Damage via
the host
immune
response
Cytotoxic T cells &
natural killer
lymphocytes
Production of measles
rash
Autoimmunity Acute Rheumatic fever
Immediate hyper-
sensitivity
Rashes associated with
helminthic infection
Cytotoxic hyper-
sensitivity
Cell necrosis induced by
hepatitis B
Immune complexes Glomerulonephritis in
malaria
Delayed type
hypersensitivity
Tuberculosis granuloma
NO. V. FACTORS USED FOR
1. Protein pilli Attachment
2. Polysaccharide/Polypeptide
capsule
Avoiding ingestion
3. Protein M Attachment
4. Outer membrane protein Attachment
5. Toxin See Toxin tables
6. Hyaluronidase Spreading
7. IgA protease Breaking Surface IgA
8. DNAse Destroying hosts cell
9. Coagulase Avoiding ingestion
Comparison of Properties
Sources Certain sp of Gram-pos &
Gram-negative
Cell wall of Gram-
negative
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 60
o
C
(except Staphyl enterotoxin)
Stable at 100
o
C for 1 hr
Typical diseases 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
9. Lecithinase cleaves cell membranes: Clost.
perfringens
10. An adenylate cylase: edema factor of Bacilus
anthracis
11. A protease: lethal factor of Bacilus anthracis
7. Inhibits chemokine receptor: Bordetella pertussis
6. Inhibits acetylcholine release: Clost. botulinum
8. Protease cleaves desmosome in skin: Staph. aureus
(scalded skin syndrome)
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 Target Effects
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 Perfringoly-
sin-O
Many cells
types
Gas gangrene
A-B type
toxins
Cl. tetani Tetano-
spasmin
Synaptic
transmission
Spastic paralysis
C. diphtheriae Diphtheria
toxin
Many cells
types
Paralysis
Vibrio cholerae Cholera toxin Intestinal
cells
Profuse watery
diarrhea
Super-
antigen
Str. pyogenes Streptococcal
pyogenic
exotoxin
T. cells,
macrophage
Fever, eruption,
toxic-shock like
syndrome
Staph. aureus Toxic shock
toxin
T. cells,
macrophage
Toxic shock
syndrome
1. Encounter entry
2. Attachment to host cells
3. Invasion
4. Multiplication
5. Dissemination
Directly
-hematogenously
--lymphatogenously
Indirectly
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 10
5
Shigella spp. Oral 10 - 1000
Vibrio cholerae Oral 10
8
Mycobacterium
tuberculosis
Inhalation 1 - 10
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
1. Normal Flora
2. Transmission of Bacteria
FURTHER READING
Brooks, GF., Butel, JS., Morse, SA. Jawetz, melnick, & Adelbergs
Medical Microbiology. 23
rd
Edition, International Edition, McGraw-
Hill, Singapore, 2004.
Cohen, J. et al. I nfectious Diseases, 2
nd
Edition, Mosby, Sydney, 2004.
Inglis, T.J.J. Microbiology and I nfection, a clinical core text for
integrated curricula with self-assessment, Churchill-Livingstone,
Sydney, 2003.
Levinson, W. Review of Medical Microbiology and I mmunology, 9
th

Edition, McGraw Hill-Lange, Singapore, 2006.
Joklik, WK., Willett, HP., Amos, DB., Wifert, CM. Zinsser
Microbiology, 20
th
edition, Appleton & Lange, Connecticut, 1992.
Mims, C., et al. Medical Microbiology, 3
rd
Edition, Mosby, Sydney,
2004.
Nath, S.K., Revankar, S.G. Problem Base Microbiology, Saunders-
Elsevier, 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 I nfectious Diseases, 3
rd
Edition, Edited.,
Williams and Wilkins, Baltimore, 1997.