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Microorganism

Ubiquitous
Most are free living
Derive their nutrition from
inert inorganic organic
materials
Association with humanharmonious, benign, and
often vital to life
Opportunist pathogens: can
establish in compromised
individuals
Pseudomonas aeruginosa
Staphylococcus aureus
Obligate Pathogens
Animals or plants are the
only reservoirs for their
existence
Nesseria gonorrhea
Mycobacterium tuberculosis
Treponema pallidum
Viruses
Must parasitize host cells in
order to replicate and are
therefore inevitably
associated with disease
Other groups may cause disease
through ingestion of substances
(toxins) produced during
microbial growth on foods
Clostridium botulinumBotulism
Bacillus cereus-Vomiting
Organisms themselves
proliferate in the host for the
effects of the toxin to be
manifested
Infection
Microorganisms must remain
associated with the host
tissues and increase their

numbers more rapidly than


they can be either eliminated
or killed
This balance to the ability of
the bacterium to mobilize
nutrients and multiply in the
face of innate of defense and
a developing immine
response by the patient
The greater the
number of bacterial
cells associated with
the host, the greater
will be the chance of
disease
If the pathogen does
not arrive at the portal
of entry to the body,
then an infection will
not ensue
Minimum Infective
Number-the minimum
number of viable
microorganisms that is
required to cause
infection and thereby
disease
o Varies markedly
between the
pathogens and
affected by
general health
and overall status
o Includes
Initial
contact
with the
pathogen
Its
consolidatio
n and
spread
between
within the

organs and
its eventual
elimination
Growth and consolidation
Commonly involves the
formation of microcolony
Microcolony and biofilms- are
collections of microorganisms
that are attached to surfaces
and enveloped with the
exopolymers (biofilm matrix)
composed of
polysaccharides,
glycoproteins and or proteins
Biofilms protect the
pathogens against
opsonization and
phagocytosis by the host but
also modulates their
microenvironment and
reduces the effectiveness of
many antibiotics
Localized high cell densities
present within the biofilm
also initiate production of
extracellular virulence factors
such as toxins, proteases,
siderepohores (low molecular
weight ligands responsible
for the solubilization and
transport of iron (III) in
microbial cells)
Quorum sensing-help the
pathogen to combat the
hosts innate defenses and
also promote the acquisition
of nutrients
Viruses
Incapable of growing
extracellularly and must
therefor rapidly gain entry to
cells (normally epithelial) at
their initial site of entry

Once internalized, they are to


a large extent protected
against the non-specific host
defenses
Organisms may expand into
surrounding tissues and
disperse to the blood,
plasma, lymph node or
nerves, to distant tissues in
order to establish secondary
sites of infection or to
consolidate further

Human Microbiome
Axenic state- the body is free
from microorganisms
Mutualistic relationship-occur
when both organisms
(microbial and host cell)
benefit from the interactions
Commensalism- is a state in
which one member of the
relationship benefits without
significantly affecting the
other
Microbiome- microorganisms
that colonize body surfaces
(internal and external)
without normally causing
disease

Comprises a number
of distinct microbiotas
which are characteristic
region of the body
colonize

Present throughout
life

Comprise of
bacteria, fungi, and
protozoa, majority is
commensal

Begins to develop
when the amniotic
membrane surrounding
the unborn child ruptures


Candida albicans- a
minority member of the
normal microbiota grow
more prolifically resulting
to vaginal yeast infection
such as candidiasis

GIT- recolonization
by desired species can be
encouraged by probiotics

Probiotics- live
cultures of intestinal
bacteria that are marketed
as conferring a health
benefit and preventing
digestive problems

Prebiotics- fibre like


carbohydrates that
represent preferred or
selective growth
substrates for probiotic
bacteria already present
within the digestive tract

Portals of Entry
Skin
Part of the body most
exposed to microorganisms
and its surface is of acid pH
and contains relatively few
nutrients that are
unfavorable for microbial
growth
Commensals- derive
nutrients from compounds
like urea, hormones and fatty
acids found in apocrine and
epocrine secretions

Adapted to growth
in the environment and
will normally prevent
establishment of chance
contaminants of the skin

Coryneform bacteria

Staphylococci

Yeasts
Sources of infection in skinPenetrate epidermis

Ringworm
( Tricophyton
mentagrophytes)

Warts (Human
papillomavirus, HPV)
Hospital acquired infectiondue to devices and implants
that are contaminated

Staphylococcus
epidermidis- grows as an
adhesive biofilm on the
surfaces of the devices
and infection arises either
from contamination of the
device during the
implantation or by growth
along it of the organism
from the skin

Bacteraemiapresence of bacteria in the


blood bc biofilm sheds
bacterial cells to the body
Achilles heels-weak spots of
the body, occur where the
skin ends and mucous
epithelial tissues begin
(mouth, anus, eyes, ears,
nose, urinogenital tract)
Mucous membranes- present
more favourable environment
for microbial growth

Warm

Moist

Rich in nutrients
Colonization resistancepossession of highly adapted
microbiotas which reduces
the chances of infection by
invading organisms
Resident flora- common to
particular host species

Each site can be additionally


protected by physiochemical
barriers such as extreme acid
pH in stomach and bile salts
in LI, presence of freely
circulating non-specific
antibodies and opsonins, and
macrophages and
phagocytes

Respiratory Tract
Protected against assault by
a mucociliary blanket that
envelops the upper
respiratory tract and nasal
cavity
Air contains a large amount
of suspended organic matter
and in enclosed occupied
species may hold up to 1000
microorganisms/m3
Airborne organisms- are nonpathogenic bacteria and
fungi of which the person
inhales approx. 10000 a day
Alveolar regions of the lower
respiratory tract have
additional protection through
macrophages
Success of pathogen

A pathogen must
avoid being trapped in the
mucus

If deposited in the
alveolar sacs it must avoid
phagocytosis by
macrophages or if
phagocytized it must
resist digestion

Surface adhesins
and epithelial receptors
aids the attachment of the
microorganism and
avoidance of removal by
the mucociliary blanket

Ciliostatic blankets
by Corynebacterium
diphteriae paralyze the
cilial bed
Mucociliary blanket-primary
defense of respiratory tract

Mucin production
from tobacco decreases
the proportion of the
ciliated epithelial cells and
increases the
susceptibility

Intestinal Tract
Extreme acidity and presence
of digestive enzymes in the
stomach will kill many
bacteria challenging it
GIT carries its own
commensal flora of yeast and
lactobacilli that afford
protection by competing with
potential pathogens just like
Helicobacter pylori
Bile salts- mixed with the
semidigested solids exiting
from the stomach into the
small intestine

These salts
neturalize the stomach
acids but also represent
biological detergents or
surfactants that are able
to solubilize the outer
membrane of gram nega
bacteria
Lower GUT is highly
populated by commensal
microorganisms and often
associated with the intestinal
walls either embedded in the
protective mucus or attached
directly to the epithelial cells
or particulate of food

Pathogenecity depends on
the pathogens ability to
survive in the stomach and
commensal microorganisms
Urinogenital Tract
Bladder, ureters, and urethra
are sterile
Sterile urine flushes the urine
tract
Organisms must avoid being
detached to the epithelial
cells
Male urethra is long- bacteria
must be introduced directly
to the bladder
Female bladder- is much
more shorter and more
readily traversed by the
microorganisms
Reflux of urine- common way
of infection of the bladder
Long term catheterization of
the bladder will promote the
occurrence of the bacteriuria
Bacteriuria- presence of
bacteria in the urine
Lactic acid-gives acidity pH 5

Inhibits colonization
by most bacteria except
some lactobacilli that
constitute the commensal
flora
Conjunctiva
Usually free of
microorganisms and
protected by the continuous
flow of secretions from the
lachrymal glands and by
frequent mechanical
cleansing of its surface by
the eyelid periphery during
blinking

Lachrymal fluids- contain


number of inhibitory
compounds and lysozyme
that enzymatically degrade
the peptidoglycan of gram
positive bacteria
Usage of soft and hard
contact lenses, physical
damage, exposure to
chemicals or damage and
infection of the eyelid border
(blepharitis)
Consolidation
Initial attachment must be
highly specific in order to
displace the commensal
microflora and subsequently
governs the course of
infection
Attachment through

Adhesive substances
such as mucopeptide and
mucopolysaccharide slime
layers

Fimbriae

Agglutinins
Secretory antibodies-directed
against such adhesions, block
the initial attachment of the
organism and thereby confer
resistance to infection
Factors that affect the
attachment

Organisms rate of
growth

Initial number
arriving at the site

Ability to resist the


efforts of the host tissues
at
removing/starving/killing
Virulence- the degree of
pathogenicity caused by the
microorganism

Virulence Factors
Nutrient Acquisition
Iron- essential for microbial
growth and function

complexed with host


iron binding proteins such
as lactoferrin or transferrin
resulting to inability of iron
the pathogens
Siderophores- iron chelating
compounds which have
greater affinity for iron than
that the hosts iron binding
proteins
Ps aeruginos- possess three
or more different
mechanisms of iron capture
Secretion of hydrolytic
enzymes- release iron from
the host
Biofilms functional microbial
community
Means of survival of the
pathogens in favorable
environment without getting
washed away
Bacterial cell numbers and
activities can become quite
high
Can form on any surface and
may contain only one or two
species
Quorum sensing- intracellular
signaling molecules are
produced that when sufficient
concentrations are reached,
up- regulate biofilm specific
genes and responsible for the
formation and maintenance
of the biofilm
Impossible to remove

Resist physical forces,


phagocytosis and penetration
of toxic molecules such as
antibiotics
Allow cells to live in close
proximity to each other with
intercellular communication
and genetic exchanges
Provide foci of infection
Resistance to Host Defenses
The inability of bacteria to
combat the hosts defenses is
the reason confine
themselves to the surface of
the epithelial tissue
Survival is due to firm
attachment
Production of toxinsmanifestation of disease
Systemic infections- ability to
gain entry to susceptible cells
and thereby enjoy protection
from the bodys defenses and
phagocytosis by
macrophages

Brucella abortus

Salmonella enterica
serova Typhi

Streptococcus
pyrogenes
Multiply in bodys
extracellular liquids
Modulation of the inflammatory
response
Release of cellular products
causes non-specific
inflammation associated with
dilation of blood vessels
Increases the capillary flow to
the infected site
Increased lymphatic flow
carries the organism to the
lymph nodes

Chemotactic fashionpolymorphs being


concentrated at the site of
infection which means
addition to the inflammation
and white blood cells
accumulation assoc. with
antibody binding and
complement fixation
Staph aureus- produces
mucopeptide that suppresses
inflammatory oedema
Avoidance of Phagocytosis
Resistance to phagocytosisspecific components of the
cell wall or presence of
capsules surrounding the cell
wall

M-proteins of the
streptococci

Polysaccharide
capsules of the
pneumococci

Alginate like slime of


Ps. Aeruginosa
K-antigens of E. coli and S.
enterica- can mediate
attachment into the intestinal
epithelial cells and render
phagocytosis more difficult
Microorganism coated with
antibody (opsonized) more
readily phagocytized

Due to presence on
the white blood cells of
receptors for the Fc
fragment of IgM and IgG
Avoidance of opsonizationenhance survival of pathogen
Protein A- released from
growing strains of Staph.
Aureus which acts by nonspecific binding to IgG anf Fc
region

Blocks the Fc region


of bound antibody
masking it from
phagocytes
Protein A-IgG complexes
remote from the infection
site- binds to complement
and depleting it from plasma
Survival following Phagocytosis
Death is avoided if the
microorganism are not
exposed to the killing and
digestion processes within
the phagocytes
Possible if fusion of the
lysosomes with phagocytic
vacuoles can be prevented
Growing in the vacuoles
despite lysosomal fusion
Attributed to the cell wall
components that prevent
access of the lysosomal
substances to the bacterial
membranes
Production of extracellular
catalase which neutralizes
the H2O2 liberated in the
vacuole
Killing of Phagocytes
Alternative strategy is for
the microorganism to kill
phagocytes
By production of leucocidins
which promote discharge of
lysosomal substances into
the cytoplasm of the
phagocyte rather than in
vacuole (phagocyte vs itself)
Manifestation of disease
Penetration and invasion of
tissues and organs
Pathogens with the inability
to combat defenses

consolidate further in
epithelial tissues
Small group of pathogen-fully
invasive

Permeate
subepithelial tissues and
circulated around the body
Through ingestion by the
victim

From foods

Regarded as
intoxications rather than
infections

Alleviation of toxins
rather than elimination of
pathogen
Non-Invasive Pathogens-binding
to epithelial is not essential but
increases permeation of toxins
and prolongs presence of
pathogen
Bordetella pertussis

Inhaled and rapidly


localizes on the
mucociliary blanket of the
lower respiratory tract

Localization- very
selective and thought to
involve agglutinins on the
organisms surface

Toxins produced by
the organism inhibit ciliary
movement of the
epithelial surface
Corynebacterium diphteriae

Attaches itself in
respiratory tract

Produces a diffusible
toxins of low molecular
weight, wc enters the
blood circulation and bring
about a generalized
toxemia

E coli and V. cholera- localize


in the gut wall or enter
systemic circulation

Produces toxins that


increases vascular
permeability

Results
hypersecretion of isotonic
fluids into the gut lumen,
diarrhea, dehydration
Partially invasive
Some are able to attach in
mucosal epithelia and
penetrate
Multiply within protective
environment of host
Induce disease through
erosion and ulceration of the
mucosal epithelium
(salmonella and shigella)
Entry induced by pinocytosis
Salmonellosis- inadequately
cooked food that have been
kept incorrectly

Dependent upon the


severity of the lesions
induced in the gut
Influenza and common
cold(rhinovirus)

Infect epithelium of
respiratory and
nasopharynx

Release of virus is
the void after the lysis
Fully invasive pathogens
Aggressively invade the
tissues in the primary site of
infection (active spread)
Transported to the body in
the blood etc (passive)
Active spread
Through normal subepithelial
tissues is difficult bc gel like

nature of intercellular
materials
Extracellular enzyme toxins

Killing of tissue cells

Degradation of
intracellular materials

Mobilization of
nutrition
Haemolysins- produces
mostly of pathogenic
staphylococci and
streptococci and have lytic
effect on red blood cells
Fibrinolysins- produced by
both staph (staphylokinase)
and strepto (streptokinase)

Toxins that activate


plasminogen and dissolve
fibrin clots
Collagenases and
hyaluronidases- produced by

most of the aggressive


invaders and capable
dissolving collagen fibers and
hyaluronic acids that function
as intercellular cements
Phospholipases-produced by
organisms such as Cl.
Perfringes and these toxins
will kill tissue cells by
hydrolyzing the phospholipids
that are present in cell
membranes
Amylases and peptidases and
deoxyribonucleases0
mobilize many nutrients that
are released form lysed cells

Decrease viscosity
of fluidsp

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