This document discusses normal flora and bacterial pathogenesis. It defines normal flora as microorganisms regularly found on body surfaces and outlines the groups of permanent and transient residents. Microflora plays both protective and nutritional roles for the host but can also cause opportunistic infections under certain conditions. The document then examines bacterial pathogenicity factors like virulence and modes of transmission. It describes common bacterial virulence mechanisms including colonization factors, anti-phagocytic factors, and exotoxins. Finally, it differentiates between exotoxins produced by bacteria and endotoxins, which are structural components of gram-negative bacteria.

1. Normal Flora and Bacterial
Pathogenesis

2. Normal Flora

3. Relationships between Organisms *
• Symbiosis, is a permanent association between two
different organisms.
• Neutralism: Two organisms living together, and neither
is affected by that.
• Mutualism: Two organisms living together, and both
benefit from that.
• Commensalism: Two organisms living together, one is
benefited and the other is not been affected.
• Parasitism: Two organisms living together, one is
benefited ‘’called parasite’’ and the other is harmed
‘’called host’’.

4. Normal flora
• Also known as microflora or microbiota.
• Normal flora defined as the mixture of microorganisms
(bacteria and fungi) that are regularly found on body
surfaces contact with outside environment (skin &
mucosa).
• By other words, normal flora refers to the population of
microorganism that inhabit in the skin and mucous
membranes of healthy normal person.

5. • There are two groups of microbiota:
a/ Permanent residents (Escherichia coli in colon), consist
of a fixed types of microorganisms regularly found in a
given area at a given age.
b/ Transient residents (Acinetobacter in urethra), which
colonizes the superficial layers of the skin, is easily to be
remove by routine hand hygiene.*

6. Microflora contributes to health:
I. Protective role (host defense) by:
(1) maintaining pH, so other organism may not grow
(2) occupying the host surface receptor, thereby
preventing binding of pathogen.
II. Serves nutritional function by synthesizing: K and B
vitamins.

7. Microflora can cause infection:
• Normal flora causes opportunistic infection in one of the
following conditions:
I. If misplaced, fecal flora to urinary tract or abdominal
cavity or skin flora to catheter.
II. Reduction of immune system, such as
immunocompromised person(AIDs/or under
immunosuppression).
III. Imbalance of normal flora, for example, antibiotics can
reduce the normal colonic flora that allows Clostridium
difficile, which is resistant to the antibiotics, to overgrow
and cause pseudomembranous colitis.

8. Sites of the normal flora

9. Site Common Less common but notable organisms
Blood, cerebrospinal fluid &
internal organs
None, generally sterile
Cutaneous surfaces including
urethra and outer ear
Staphylococcus
epidermidis
Staphylococcus aureus, corynebacteria,
Streptococci, Peptostreptococci and Yeast
(Candida)
Nose Staphylococcus aureus Staphylococcus epidermidis,
corynebacteria, Streptococci
Oropharynx Viridans streptococci Nonpathogenic Neisseria, Haemophilus
influenzae,
Stomach None
Colon Babies; breast fed only:
Bifidobacterium
Adults:
Bacteroides/ prevotella
(predominent)
Escherichia/ Various
Enterobacteriaceae
Bifidobacterium
Enterococci,
Streptococci,
Diphtheroids,
Fusobacterium,
S. aureus,
Yeast
Vagina Lactobacillus, enterococci, Enterobacteriaceae and other
gram-negative rods, S epidermidis,
Candida albicans, and other yeasts
Important normal flora in Humans

10. Bacterial pathogenicity

11. Pathogenicity*
Important terminology:
 Pathogenicity refer to the ability of an organism to
cause disease
Pathogen is microorganism capable of causing disease.
 Opportunistic pathogens are those that not cause
disease in immunocompetent people but can cause
serious infection in immunocompromised patients.
 Opportunistic refers to the ability of the organism to
take the opportunity offered by reduced host defenses to
cause disease.

12.  Virulence is the term used to describe the degree of
pathogenicity of an organism.
 LD50 (50% lethal dose ) is the number of organisms
needed to kill half the hosts.
 ID50 (50% infectious dose ) is the number of
organisms needed to cause infection in half the hosts.
 Communicable (Contagious) infection, is spreading
of infectious agent from host to host (e.g., tuberculosis)

13.  Endemic refers to the constant presence of a disease
or agent of disease in a community or region.
 Epidemic disease when it occurs much more
frequently than usual.
 Pandemic disease when it has a worldwide
distribution.*

14. Why do people get infectious diseases?.
• People get infectious diseases when microorganisms
overpower our host defenses.
• This depend on two factors:-
1. Organism's factor, Number of organism (infectious
dose) and its virulence factors.
2. Host’s factor, its immune status,
immunocompromised are more susceptible to
infection.

15. Stage of bacterial pathogenesis:
• A generalized sequence of the stages of infection is as
follows:
1. Transmission from an external source into the portal of
entry.
2. Attachment to the mucous membranes.
3. Evasion of primary host defenses
4. Colonization by growth of the bacteria at the site of
adherence.
5. Toxin production or invasion of tissue accompanied by
inflammation.
6. Host responses, both nonspecific and specific (immunity).
7. Progression or resolution of the disease.

16. Transmission:
Human-to-Human
A. Direct contact, Gonorrhea (Neisseria gonorrheae), e.g.,
sexual contact.
B. Indirect contact
• Dysentery (Shigella) Fecal-oral
C. Transplacental
• Congenital syphilis (Treponema pallidum), Bacteria cross
the placenta and infect the fetus
D. Blood-borne
• Syphilis: Transfused blood or intravenous drug use can
transmit bacteria

17. Nonhuman to human
A. Soil source
• Tetanus Spores in soil enter wound in skin
B. Water source
• Legionnaire's disease, Bacteria in water aerosol are
inhaled into lungs.
C. Animal source
• Hemolytic-uremic syndrome (E. coli O-157), Bacteria in
cattle feces are ingested in undercooked hamburger

18. Portal of entry of some common pathogenic bacteria
Portal of Entry Pathogen Disease
Respiratory tract Streptococcus
pneumoniae
Pneumonia
Neisseria meningitides Meningitis
Haemophilus influenzae Meningitis
Mycobacterium
tuberculosis
tuberculosis
Gastrointestinal
tract
Shigella dysenteriae Dysentery
Salmonella typhi Typhoid fever
Vibrio cholerae Cholera
Skin Clostridium tetani Tetanus
Clostridium perfringens Gas-gangrene
Bacillus anthracis Anthrax

19. Conti.
Portal of Entry
Portal of Entry Pathogen Disease
Genital tract Neisseria gonorrhoeae Gonorrhea
Treponema pallidum Syphilis
Chlamydia trachomatis Urethritis

20. Bacterial virulence factors:
A. Colonization factors:*
1. Pili (fimbriae): primary mechanisms in most gram-
negative bacteria.
2. Teichoic acid: primary mechanism of gram-positive
bacteria.
3. IgA protease: Enhances the bacteria attach to the
mucosal surface by cleaving IgA (Neisseria,
Streptococcus pneumoniae & Haemophilus).
4. Adhesins: e.g., Haemoagglutinin (Yersinia pestis)

21. B. Anti-phagocytic factors:
• These are bacterial surface components that inhibit the
phagocytic uptake the bacteria.
1. Capsule (Strept. pneumoniae, Klebsiella).
2. M protein (Strept. pyogenes).
C. Enzymes:*
1. Bound Coagulase: this protects the bacterial from immune
system by formation of fibrin clot around the bacteria (e.g., S.
aureus).
2. Collagenase: Breakdown the host collagen fibers.
3. Hyaluronidase: breakdown hyaluronic acids which ground
substance of connective tissue.
4. Proteinase: Destroy the host proteins.
5. Lipases: breakdown of lipids

22. D. Exotoxins:*
1. Leukocidins, which can destroy both neutrophilic
leukocytes and macrophages.
2. Hemolysin: which lysis RBCs, neutrophils and
platelets.

23. Exotoxins:
• They are produced by several gram-positive and gram-
negative bacteria.
• These are extracellular proteins that encoded by genes
located in plasmids or lysogenic bacteriophage.*
• Exotoxins are good antigens that induce protective
antibodies called antitoxins (e.g., tetanus).
• Exotoxin can converted into toxoid (vaccine)when
treated with formaldehyde, acid or heat.
Bacterial Toxins
The bacteria cause disease by productions of toxins (exotoxin
& endotoxin).

25. Endotoxin:
• Endotoxins are parts of the cell walls of gram-negative
bacteria.
• They are lipopolysaccharides (LPS).
• The enzymes that produce the LPS are encoded by
genes on the bacterial chromosome.
• The toxicity of endotoxins is low in comparison
with that of exotoxins.
• Endotoxins are weakly antigenic.
• No toxoids have been produced from endotoxins.

26. LPS
Complement cascade
C3a C5a
Vasodilatation
Hypotension
Neutrophil
chemotaxis
Tissue factor
Thrombosis
Disseminated
intravascular
coagulation (DIC)
Platelets activation and adhesion
Fever
Hypotension (shock)
DIC: rash, ischemia and organ failure
LPS
Effects of Endotoxin:

27. Property Exotoxin Endotoxin
Source Both Gram-positive and
Gram-negative bacteria
Only Gram-negative
Secreted from cell Yes No
Chemistry Polypeptide LPS
Location of gene Plasmid or
bacteriophage
Bacterial chromosome
Toxicity High Low
Clinical effects Various effect Fever, Shock
Mode of action Specific Nonspecific
Antigenicity Immunogenic Poorly antigenic
Vaccines Can be converted into
toxoids
Can not be converted
into toxoids
Heat stability Labile (except S. aureus
enterotoxin)
Stable

28. Typical stages of bacterial diseases
1. The incubation period, which is the time between the
acquisition of the organism (or toxin) and the beginning
of symptoms (this time varies from hours to days to
weeks, depending on the organism).
2. The prodrome period, during which nonspecific
symptoms such as fever & malaise occur.
3. The specific-illness period, during which the
characteristic symptoms and signs appear.
4. The recovery period, during which the illness disappear
and the patient returns to the healthy state.
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