Normal Flora

and
Pathogenesis
 Normal Microbial Flora
1. Resident Flora
– Microbes that are always present

2. Transient Flora

– Microbes that live in or on your body for a
period of time (hours, days, weeks,
months) then move on or die off
 Normal flora
 is the term used to describe the
various bacteria and fungi that are
permanent residents of certain body
sites
 The normal flora organisms are also

referred as commensals.
 Commensals are organisms that derive

benefit from another host but don’t

damage that host.
 Especially the skin, oropharynx,
colon, and vagina are the site of
normal flora.
 Areas such as the central nervous

system, blood, lower bronchi and

alveoli, liver, spleen, kidneys and
bladder are free of all but the
occasional transient organism.
 Viruses and parasites are usually not

consider as normal flora.

 Normal Flora
 There is distinction between
presence of organism and carrier
state.
 CARRIER state means that an

individual harbours a otential

pathogen and therefore can be a
source of infection to others. e.g. in
case of asymptomatic infections.
 Normal Flora
 There is also distinction made
between members of normal flora
which are permanent residents and
COLONIZATION of individual with a
new organism where colonization
refers to the acquisition of a new
organism.
 Normal Flora of the Skin
 Avg. adult has 2 m2 of skin surface.
 Skin is not favorable to microbial growth
since it is subject to drying.
 Most microbes are associated with the
sweat glands.

Normal Flora of the Oral Cavity

Saliva contains antibacterial enzymes, Food particles,
and epithelial debris provide nutrients for microbes.
 Normal Flora of the
Gastrointestinal Tract
The stomach is not hospitable to microbes due to its low
pH (pH 2), except Helicobacter pylori, which causes ulcers.

 E.coli - Intestinal
 Normal Flora of the Respiratory
Tract
 Upper respiratory tract = nasopharynx, oral cavity, and
throat.
 Staphylococci, streptococci, diphtheroid bacillia, and gram-
neg. cocci, as well as potentially harmful bacteria (ex.
Staph. aureus and Strep. Pneumoniae) are often part of
the normal flora of the nasopharynx of healthy individuals.

 Lower respiratory tract = trachea, bronchi, and lungs.

The lower respiratory tract is essentially sterile. Ciliated
epithelium beat contaminants upward.
 Normal Flora of the Urogenital
Tract
 The bladder itself is usually sterile, but the epithelial cells lining
the urethra are colonized by facultatively aerobic gram-neg. rods
and cocci, including E. coli, Proteus mirabilis, etc.

 Occasionally, these organisms become opportunistic pathogens.

Factors such as local pH changes allow organisms to multiply
and become pathogenic.

 The vagina of the adult female is generally weakly acidic and
contains significant amounts of the polysaccharide glycogen.
Lactobacillus acidophilus, yeasts such as Candida, streptococci,
and E. coli may also be present. Before puberty (the vagina is
alkaline and does not produce glycogen. L. acidophilus is absent
at this time. After menopause, the flora resembles that before
puberty.
 Importance of normal flora in
health and disease
 Can cause disease, especially in
immunocompromised and debilitated
 Nonpathogens in their usual anatomic
location they can be pathogens in other
parts of the body
 Constitute a protective host defense
mechanism – occupy attachments sites on
skin mucosa that can interfere with
colonization by pathogenic bacteria –
colonization resistance
THE BENEFITS OF THE NORMAL
FLORA - 1
 The normal flora synthesize and
excrete vitamins in excess of their
own needs, which can be absorbed
as nutrients by the host. For
example, enteric bacteria secrete
Vitamin K and Vitamin B12, and lactic
acid bacteria produce certain B-
vitamins.
 THE BENEFITS OF THE NORMAL
FLORA - 2
 The normal flora prevent colonization by
pathogens by competing for attachment
sites or for essential nutrients. This is thought
to be their most important beneficial effect,
which has been demonstrated in the oral
cavity, the intestine, the skin, and the vaginal
epithelium.
THE BENEFITS OF THE NORMAL
FLORA - 3
 The normal flora may antagonize
other bacteria through the
production of substances which
inhibit or kill nonindigenous species.
The intestinal bacteria produce a
variety of substances ranging from
relatively nonspecific fatty acids and
peroxides to highly specific
bacteriocins, which inhibit or kill
other bacteria.
THE BENEFITS OF THE NORMAL
FLORA - 4
 The normal flora stimulate the
production of cross-reactive antibodies.
Since the normal flora behave as antigens in
an animal, they induce an immunological
response, in particular, an antibody-mediated
immune (AMI) response. Low levels of
antibodies produced against components of
the normal flora are known to cross react
with certain related pathogens, and thereby
prevent infection or invasion.
 Introduction of Bacterial
Pathogenesis
1. Infection: growth and multiplication of a
microbe in or on the body with or without
the production of disease.

2. The capacity of a bacterium to cause

disease reflects its relative
“Pathogenicity.”

3. Opportunistic pathogens are those that

rarely, if ever, cause disease in
immunocompetent people but can
cause serious infection in
immunocompromised patients.
These opportunists belongs to the body's
normal flora.
 Virulence and Virulence factors
 Virulence is the measure of the
pathogenicity of a microorganism.
 Virulence factors – the various traits or
features that allow or enhance the
microorganism’s ability to cause disease.
These take may forms and include
– adhesion organelles,
– toxin production,
– evasion of the host’s immune response,
– resistance to antibiotics,
– ability to invade host tissues, and
– enhanced intracellular survival and growth
 Important terms
 Colonization: establishment of a site of
reproduction of microbes on a person without
necessarily resulting in tissue invasion or damage.
 Infection: growth and multiplication of a microbe
in or on the body of the host with or without the
production of disease.
 Carrier: a person or animal with asymptomatic
infection that can be transmitted to another
person or animal.
 Zoonosis: infectious diseases transmitted
between animals and men.
erms Used to Classify Infectious Disease
 Signs and Symptoms
 Sign – objective evidence of disease as
noted by an observer

– fever, septicemia, chest sounds, rash,

leukocytosis, antibodies

 Symptom – subjective evidence of

disease as sensed by the patient

– chills, pain, ache, nausea, itching,

headache. fatigue
 PORTALS OF ENTRY
 To cause disease, → pathogenic bacteria → gain access to
the host

 Organisms able to evade, compromise or take advantage

of a compromised innate immune system including the
primary barriers of skin and mucus membranes

 Any compromise in these barriers (cuts, ulcers, surgical

procedures, catheters, etc) may allow bacteria entrance
into the host

 Normal skin flora, including Staphylococcus aureus and

Staphylococcus epidermidis, → enter to these
compromised barriers → an infection
 Infection / entry
 Ingestion (fecal-oral)
 Inhalation (respiratory)
 Trauma (burn)
 Arthropod bite
(zoonoses: mosquito,
flea, tick, Tsetse fly)
 Sexual transmission
 Needle stick (blood
transfusion)
 Maternal-neonatal

24
For lecture only
Routes of entry for invading pathogens
Ear

Broken
skin

Insect Conjunctiva
bite of eye

Nose

Mouth

Placenta

Vagina
Anus In males:
Penis

Urethra
2. Toxin Production
 Toxins: Poisonous substances produced by microbes.
 Frequently toxins are the main pathogenic factor.
 Toxigenicity: Ability of a microbe to produce toxins.
 Toxemia: Presence of toxins in the blood.
 Toxin effects: May include fever, cardiovascular
problems, diarrhea, shock, destruction of red blood
cells and blood vessels, and nervous system
disruptions.
 Of 220 known bacterial toxins, 40% damage eucaryotic
cell membranes.
 Two types of toxins:
– Exotoxins
– Endotoxins
Exotoxins versus Endotoxins
A. Exotoxins
– Proteins: Enzymes that carry out specific reactions.
– Soluble in body fluids, rapidly transported throughout
body in blood or lymph.
– Produced mainly by gram-positive bacteria.
– Most genes for toxins are carried on plasmids or
phages.
– Produced inside bacteria and released into host tissue.
– Responsible for disease symptoms and/or death.
 Cytotoxins: Kill or damage host cells.

 Neurotoxins: Interfere with nerve impulses.

 Enterotoxins: Affect lining of gastrointestinal tract.

– Antibodies called antitoxins provide immunity.

– Toxoids: Toxins that have been altered by heat or
chemicals. Lose the toxicity and retain their antigenic
ability. Used as vaccines for diphtheria and tetanus.
 Important Exotoxins
 Diphtheria Toxin: Corynebacterium diphtheriae
when infected by a phage carrying tox gene.
Cytotoxin inhibits protein synthesis in eucaryotic
cells. Two polypeptides: A (active) and B (binding).

 Erythrogenic Toxins: Streptococcus pyogenes

produces three cytotoxins which damage blood
capillaries, causing a red rash.

 Botulinum Toxins: Produced by Clostridium

botulinum. Neurotoxin that inhibits release of
neurotransmitter acetylcholine and prevents
transmission of nerve impulses to muscles, causing
flaccid paralysis. Extremely potent toxins.
 Important Exotoxins
 Tetanus Toxin: Produced by Clostridium tetani. A
neurotoxin that blocks relaxation of skeletal
muscles, causing uncontrollable muscle spasms
(lockjaw) and convulsions.

 Vibrio Enterotoxin: Produced by Vibrio cholerae.

Two polypeptides: A (active) and B (binding). The
A subunit of enterotoxin causes epithelial cells to
discharge large amounts of fluids and electrolytes.

 Staphylococcal Enterotoxin: Staphylococcus

aureus produces an enterotoxin similar to cholera
toxin. Other enterotoxins cause toxic shock
syndrome.
 Rash of Scarlet Fever Caused by
Erythrogenic Toxins of Streptococcus
pyogenes
Muscle Spasms of Tetanus are Caused
by Neurotoxin of Clostridium tetani
Vibrio Enterotoxin Causes Profuse Watery Diarrhea

Rice-water stool of cholera. The A subunit of enterotoxin causes

epithelial cells to discharge large amounts of fluids and electrolytes.
 Diseases Caused by Staphylococcal Toxins

Scalded Skin Syndrome Toxic Shock Syndrome

 Endotoxins
 Part of outer membrane surrounding gram-
negative bacteria.
 Endotoxin is lipid portion of lipopolysaccharides
(LPS), called lipid A.
 Effect exerted when gram-negative cells die and
cell walls undergo lysis, liberating endotoxin.
 All produce the same signs and symptoms:
 Chills, fever, weakness, general aches, blood
clotting and tissue death, shock, and even death.
Can also induce miscarriage.
 Fever: Pyrogenic response is caused by
endotoxins.
 Endotoxins (Continued)
 Endotoxins do not promote the formation of effective
antibodies.

 Organisms that produce endotoxins include:

– Salmonella typhi
– Proteus spp.
– Pseudomonas spp.
– Neisseria spp.

 Medical equipment that has been sterilized may still

contain endotoxins.

 Limulus amoebocyte assay (LAL) is a test used to

detect tiny amounts of endotoxin.