Host-microorganism integration

and pathogenicity
 ? What is pathogenicity
.It is the capacity of microbes to initiate disease

?What does pathogenitity require

It requires transmissibility or communicability
from one host or reservoir to a fresh host,
survival in a new host, infectivity or the
ability to breach the new host's defenses and
virulence, a variable that
is multifactor and denotes the capacity of
.pathogen to harm the host
 ? What is virulence
It is a manifestation of a complex parasite-host disease
.is considered in relation to resistance of the host

From the organism's

:From the host's perspective
:perspective

the two clinical determinants in

the two main arms of own-host
harming the host are the number
defenses
of organisms to which the host is
are innate immunity and acquired
exposed to (load) and the
.immunity
.virulence of these organisms
 -:Types of Bacterial pathogens
.A- Opportunistic pathogens
B- Primary pathogens
Primary pathogens
They are capable of establishing
infection and causing disease in
previously healthy individuals with
intact immunological defense
Opportunistic pathogens
They rarely cause disease in
individuals with intact
immunological and intact
anatomical defense. Only when such
defense are impaired as a result of
congenital or acquired disease or by
the use of immunosuppressive
therapy or surgical techniques, these
bacteria are able to cause disease.
Many of the opportunistic pathogens
.are normal flora
 Keep in mind

Not all strains of a particular bacteria species are

equally pathogenic.

 Different strains of pathogenic species may

cause distinct types of infections, each associated
with possession of particular virulence
determinants.
 :Types of bacterial infections

toxin production-1
invasion and inflammation-2
 :Stages of bacterial pathogenesis
Transmission from external source into the portal -1
.of entry
Envasion of primary host defenses such as skin. -2
3- Adherence to mucous membranes usually by
.bacterial pili
Colonization by growth of bacteria at the site of -4
.adherence
.Disease signs and symptoms -5
Host responses, both non-specific and specific. 7- -6
.Progression or resolution of the disease
 -:Determinants of bacterial pathogensis

: A) TRANSMISSION
B) Adherence to cell surfaces through specialized structure
as pili or production of substances as capsules or
: :glycocalyxes for examples

C- Invasion, inflammation and intracellular survival:

Several enzymes secreted by invasive bacteria play a role
-:in their pathogenesis

:D- Toxin production

-:Determinants of bacterial pathogens
: A) TRANSMISSION
Mode of transmission is extremely important it
could be human to human, non-human source
such as soils water and animals, fomites which are
.inanimate objective such as towels
 :human-to-human-1 Non-human to human-2

:A. Direct contact

A. soil source
.as sexual or passage through birth canal
e.g. tetanus
:B. No direct contact
b. water source
.as fecal-oral
.e.g. Legionella
C. Transplacental
:c. Animals source
.such as congenital syphilis
.Directly as cat scratch disease -1
D. Blood borne
.Via insect vector as in tick bite-2
as hepatitis C and HIV viruses
.Via animal excreta e.g. E.coli-3
d. Fomite source
e.g. staphylococcal skin infections in
which bacteria on objects e.g. a towel
.are transferred onto the skin
-:Determinants of bacterial pathogens
B) Adherence to cell surfaces through specialized
structure as pili or production of substances as capsules
: :or glycocalyxes for examples

1. The pili of Neisseria gonorrhea and E.coli

medicate the attachment of organisms to
urinary tract epithelium.
2. The glycocalyxes of staphylococcus epidermidis
allows the organisms to molecules that mediate
adherence to cell surfaces are called adhesion.
-:Determinants of bacterial pathogens
C- Invasion, inflammation and intracellular survival:
Several enzymes secreted by invasive bacteria play a
-:role in their pathogenesis

1. Collagenase and hyalorunidase;

especially important in cellulitis caused by streptococcus
.pyogens
:Coagulase .2
.produced by staph. Aureus
:IgA protease .3
produced by Neisseria gonorrhea, Haemophilus influenza
.and strept.pneumoniae
:Leukocidins .4
?which can destroy neutrophils and macrophage
 Bacteria can cause two types of
inflammations:
1. Pyogenic:
neutrophils predominate e.g. most G+ve and G-ve.
2. Granulomatous:
macrophages and T-lymphocytes predominate e.g.
mycobacteria tuberculosis.
Intracellular survival is important attribute of certain bacteria
that enhances their ability to cause disease. E.g. mycobacteria
tuberculosis TB, brucella, and listeria.

The genes that encode many virulence factors in bacteria

chromosome. And found in many G-ve bacteria such as E.coli,
salmonellae, vibrio cholera and pseudomonas. And in G+ve
bacteria such as streptococcus pneumonia.
-:Determinants of bacterial pathogens
:D- Toxin production

Exotoxins Endotoxins
 :D- Toxin production

Exotoxins

they are produced by certain species of G+ve and G-ve

bacterias and secreted by bacterial cells.
Extoxins are of high toxicity (fatal dose is order of 1 μg)
Exotoxins are polypeptide whose genes are frequently located
on plasmids or bacteriophages.
Exotoxins are good antigens and induce synthesis of protective
antibodies called (antitoxins), some of which are useful in
prevention or treatment of disease.
When treated with formaldehyde (or acid, heat) The exotoxins
converted into toxoids which are used in protective vaccines
because they retain their antigenicity but have lost their
toxicity.
Typical examples: Tetanus, botulism, Diphtheria, Cholera,
Brodetella pertussis, E.coli.
 :D- Toxin production

Endotoxins

Are integral parts of the cell walls of both G-ve rods and cocci only
Not present in G+ve bacteria. Not secreted from cells. Endotoxin
composed of lipopolysaccharide (LPS) which are produced by
enzymes encoded by genes on bacterial chromosome rather than
by plasmid or bacteriophage.
The toxicity of endotoxins is low.
All endotoxins produce the same generalized effects of fever and
shock.
Endotoxins are weakly antigenic, they induce protective
antibodies so poorly.
No toxoids have been produced from endotoxins.
Endotoxins are not used as antigens in any available vaccine. The
main component of LPS is lipid A.
:The biological effects of endotoxins include

1- Fever: by release of endogenous pyogens as

interleukin and tumor necrosis factor from
macrophages.
2- Hypotension, shock and impaired perfusion of
essential organs.
3- Disseminated Intravascular Coagulation
(DIC) and toxic shock
Typical example is
meningococcemia Caused by Neisseria meningitides.
 :Typical stages of an infectious disease
:The incubation period -1
it is the time between the acquisitions of the organism and
beginning of symptoms (it varies from hours to days to weeks).
2- The prodromal period:
during which non-specific symptoms such as fever, malaise and
loss of appetite occur.
3- The specific-illness period:
during which the overt characteristic signs and symptoms of the
disease occur.
4- The recovery period:
during which the illness abates and the patient returns to the
healthy state.
 Normal flora
it is used to describe the various bacteria and •
fungi that are permanent residents of certain
body sites especially the skin, colon, oropharynx
.and vagina
The viruses and parasites are usually not considered members
of normal flora, although they can be present in asymptomatic
.Individuals
The members of normal flora vary in both number and kind from one
. to another site
Although the normal flora extensively populates many areas of the
body, the internal organs usually are sterile such as CNS, blood, lower
bronchi, alveoli, liver, spleen, kidneys and bladder are free of all but
.the occasional transient organism
There is a distinction between the presence of these
organisms and the carrier state.

Carrier implies that an individual herbors a potential

pathogen and therefore can be a source of infection
of others. It is most frequently used in reference to a
person with an asymptomatic infection or to
someone who has recovered from a disease but
continues to carry the organisms and may shed it for
a long period.

There is also a distinction between members of

normal flora and the colonization of the individual
with a new organism.
We are all colonized by normal flora but the term
colonization means acquisition of a new
organism, which may cause infectious disease or
be eliminated by our host defenses.
The members of the normal flora play a role both in the
maintenance of health and in the causation of disease in
three significant ways:

They can cause disease, especially in immunocompromised -1

.individuals

They constitute a protective host defense mechanism, the -2

nonpathogenic
resident bacteria occupy attachment sites on the skin and
mucosa that can interfere with colonization by pathogenic
.bacteria

They may serve a nutritional function. The intestinal -3

bacteria
produce several B vitamins and vitamin K.
 Normal flora of the Normal flora of the
-:Genitourinary tract :respiratory tract
Normal
flora
Normal flora of the Normal flora of
-:skin :intestinal tract
 -:Normal flora of the skin

a- Staphylococcus epidermidis,
which is nonpathogenic on the skin
but can cause disease when it reaches certain sites such as artificial
heart valves and prosthetic joints.

b- Anaerobic organisms
such as propionibacterium and peptococcus,
which is implicated is the pathogenesis of acne.

c- The yeast, candida albicans,

which can enter a person blood stream
when needles pierce the skin (e.g. in patient with intravenous
catheters or in IV drug users). And it is important cause of systemic
infections in patients with reduced cell-mediated immunity.
:Normal flora of the respiratory tract
-Wide spectrum of organisms colonize the nose, throat
and mouth but the lower bronchi and alveoli typically
contain few, if any, organisms.

-The nose is colonized by a variety of streptococcal and

staphylococcal species, the most significant of which is
pathogen staphylococcus aureus . it occasional
outbreaks of disease due to this organism e.g. in the new
born nursery, can be traced to nasal , skin or perianal
carriage by personnel.

-The throat is colonized by viridans streptococci, Neisseria

species and staphylococcus epidermidis.
The mouth is colonized by viridans streptococci make
about half of the bacteria.

Streptococcus membrane, member of viridans group

found in large number in dental plaque, the precursor of
caries.

Viridans streptococci are leading cause of subacute

bacterial endocarditis which enters the blood at the time
of dental surgery and attached to damaged heart valves.

Anaerobic bacteria such as bacteria bacteriodes,

clostridium is found in gingival crevices.
Actinomyces israeeli an anaerobic organism that can
cause abscesses of jaw, lungs or abdomen
:Normal flora of intestinal tract
Colon is the major location of bacteria in the body.
Roughly, 20% of feces consist of bacteria.
The major bacteria are E.coli, Coliform,
bacteriodes, Lactobacilli and Clostridium.
-:Normal flora of the Genitourinary tract

The vaginal flora of the adult women consists primarily of

lactobacillus species.

Vagina is located close the anus and can be colonized by

members of the fecal flora, such as E.coli.

About 20% of woman at childbearing age carry group B

streptococci in the vagina which is the important cause of
sepsis and meningitis in new born acquired through
passage in birth canal.

Candida albicans is part of normal flora of the

genitourinary tract in both male and female.
 Summary of the members of normal flora
and their anatomic location
-:Colon
Bacteroides species, Clostrium species, Enterococcus faecalis
,Escherichia coli ,coliforms,lactobacillus species ,Pseudomonas
aeruginosa ,Bacteroides fragilis, Escherichia coli
-:Throat
Viridans streptococci
-:Vagina
Bacteroides species ,Candida albicans ,Corynebacterium
species(diphtheroids), Escherichia coli, coliforms, Gardnerella
vaginalis, lactobacillus species, Staphlyococcus epidermidis, group B
streptococci
-: Nasopharynx
Corynebacterium species(diphtheroids),Haemophilus species, Neisseria
species ,Viridans streptococci
-:Mouth
Candida albicans, lactobacillus species, Neisseria species, Viridans
streptococci
-:Skin
Corynebacterium species(diphtheroids),Propionibacterium,
Pseudomonas aeruginosa ,Staphyloccous epidermidis
-: Urethra
-:epidermidis Less Important Organisms
Staphyloccous
S.epidermidis ,Corynebacterium(diphtheroids),Various streptococci
,Various gram negative rods, e.g. E.coli
-:Conjunctiva
Haemophilus species
-:Nose
Staphyloccous epidermidis, staphylococcus aureus
-:Dental plaque
Streptococcus mutans
-:Gingival crevices
Various anaerobes , e.g. Bacteroids,Fusobacterium,streptococci,
Actinomyces
The End