Microbiology, Lecture 14+15

8/7/2019 Microbiology, Lecture 14+15

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Pathogenesis of infection Dieses

Done by :

Sara alomari

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Pathogenicity by definition means the ability to cause

disease .

Pathogenesis refers to the whole steps or mechanisms

involved in the development of a disease ..

infectious disease is a disease caused by a microbe, and

the microbes that cause infectious diseases are collectively

referred to as pathogens

many microbiologists , reseve use the word infection to

mean COLONIZATION by a pathogen ..

so the pathogen may or may not go on to cause disease;

in other words A person can be infected with a pathogen,

but not develop disease. Or not have the infectious disease

caused by pathogens ...

so Why Disease Does Not Always Occur ??

many people who exposed to pathogens not always get sick

... this is due to many reasons ..::

_ The microbe may land at an anatomic site where it is

unable to multiply ..

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Ex : when a respiratory pathogens land in the skin it

cant grow because the presence of fatty acid and lack of

moisture and nutrients ...

_ Many pathogens must attach to specific receptor sites

before they are able to multiply

and cause damage so if they land at a site where receptor

are absent they are unable to cause disease ...

_ Antibacterial factors may be present at the site where

the pathogen lands .that inhibit or destroy the growth of

bacteria ..

Ex > the lysozyme that is present in tears .. that is why

bacteria can not cause infection in eyes ..

_ Indigenous microflora of that site may inhibit growth of the

foreign microbe (i.e., microbial antagonism). That inhibit the

growth of foreign microbe by occupying space and using up

nutrients.. Or it can produce a Bacteriocinsthat kill the

newly arrived pathogens..

_ the person health status .. EX. The person who is in

good health with no medical problems would be less likely

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to become infected than that the person in poor health.. Or

the person may be immune to that pathogens by having

vaccinated for example...

_ the presence of WBCs that destroy and engulf the

pathogens before multiply ..

Now once pathogen can enter the body the infectious

disease will has four periods ::

1- The Incubation period : the time between arrival of

pathogens and the symptoms start to appear ..

2- The prodromal period : the patient may feel they are

coming down with something but actually he dont yet

know what ...

3- The period of Illness : the typical and actual symptoms

that associated with particular disease

4- The convalescent period :the time during the recovery

of the person ..

Now once the infectious process initiated may remain

localized such as boils abscess and pimples or it may

spread and carried to other part of the body and involve

the lymph and blood.. And this is we called Systemic

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disease Orgeneralized infection. ex >> Mycobacterium

tuberculosis. Spread to many internal organs..

The disease may be acute that has a rapid onset, and is

usually followed by a relatively rapid recovery

examples are measles, mumps, and influenza

orchronic which has a slow onset and last for a long time

examples are tuberculosis, leprosy, and syphilis.

OrA sub acute which is that comes on more suddenly

than a chronic disease, but less suddenly than an acute

disease; an example would be bacterial endocarditis.

Sometimes disease may go from symptomatic to

Asymptomatic and then after a time later will go back to

being symptomatic this is called Latent disease

Examples include syphilis and herpes virus infections such

as cold sores,

genital herpes, and shingles.

Now some evidence of a disease that is experienced by the

patient; something that is subjective is called A symptom of

a disease.

There are symptomatic and asymptomatic diseases. In a

symptomatic disease, the patient is experiencing symptoms.

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In an asymptomatic disease, the patient is not experiencing

any symptoms.

But A sign of a disease is defined as some type ofobjective evidence of a disease; for example,elevated blood

pressure, abnormal heart sounds, abnormal pulse rate,

abnormal laboratory results

One infectious disease may commonly follow another; in

such cases, the first disease is referred to as a primary

infection and the second disease is referred to as a

secondary infection.

Example: serious cases of bacterial pneumonia frequently

follow mild viral

respiratory infections.

During the primary infection, the virus causes damage to

the ciliated epithelial

cells of the respiratory tract; these cells are then unable to

clear opportunistic

bacterial pathogens from the respiratory tract, leading to the

secondary infection (e.g. pneumonia).

In General the pathogenesis follows this sequence in order

to cause infectious disease

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1.Entry of the pathogen into the body. And penetrating the

skin and mucous membrane , provide the primary defense

against infection.

Frequent portals of entry of pathogenic bacteria:

_ Respiratory (upper and lower airways)

_ Gastrointestinal (primarily mouth)

_ Genital and urinary tracts.

_Abnormal areas of mucous membranes and

skin (e.g. cuts, burns, and other injuries) are

also frequent sites of entry.

2.Attachment of the pathogen to some tissue(s) within the

body

3.Multiplication of the pathogen.

4. Invasion or spread of the pathogen.

5.Evasion of host defenses.

6.Damage to host tissue(s)

so a common way for spreading is directly by invading the

tissue .. So some bacteria and viruses can enter and go

directly through a tissue and others basically will be carried

by a lymphatic tissue and from there will be carried to

blood circulation

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In the case of bacteria >> bacteremia

And viruses >> virimia

once it reach the blood it can wide spread or potentially

reach all tissue and organ of the body but usually pathogen

has specific tropism to specific tissue and organ .

thats why hepatitis virus cause hepatitis and not for

example meningitis bcoz it likes to infects the liver cells and

not brain cells or meninges cells

now ..

to give u an idea about a general life cycle of a pathogen I

will told u the brief history or a brief description of a life

cycle of streptococcus pneumonia which can lead to

pneumonia and also other infection ..

so this is just for ur own info. And the next slide also for

ur info. About vibro colera which leads to colera which is

very sever form of watery diaria ...

A next important topic is virulence and virulence factor..

So the term virulence is sometimes used as a synonym for

pathogenic

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There may be virulent (pathogenic) strains and avirulent

(nonpathogenic) strains of a particular species.So when we

say we have a virulent bacteriam that means its apathogenic bacteriam that casing human dieses .. or more

likely to cause human disease than a non virulent or non-

pathogenic stage for the same bacteria or viruses ...

for example .we have a bacteria called

Corynebacterium diphtheriae some of these bacteria have a

gene for specific diphtheria toxin production .. so if u

colonies by this bacterium this bacteria will start to produce

toxin and will cause the disease so we called this type of

bacteria a pathogenic or a virulent bacterium ..

and also we have strains a similar that not contain a gene

of toxin production is considered to be a non pathogenic or

non virulent strain ..

so Virulent strains are capable of causing disease; avirulent

strains are not.

also Sometimes, the term virulence is used to express the

measure or degree of pathogenicity.

So we can compare 2 different pathogenic bacteria and

say this bacteria is more virulent or more pathogenic than

another type of bacteria ..

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For example..Salmonella need to ingest 100- 1000 cells to

cause salmonolosis.. Whereas shigella we need to

ingest only 10 cells to case shigellosis;So shigella is calledmore virulent or more pathogenic than salmonella because

we need less cell to cause human disease; Also another

example is Streptococcus Pyogenes :Some strains can

produce enzyme toxin that allow them to destroy human

tissue so these strain are called fleshy strain and

considered to be more virulent than the strains that can't

produce this enzymes and toxin that destroy the human

tissue ...

So atrofiels that allow the bacteria to be virulent or non

virulent are called the virulence factor. So these are the

phenotypic characteristics for the pathogen .. and these are

basically an expression of a genotype ..

So virulence factor can't be express in air they need to

have specific gene within the genome of the virus or the

bacteria to express these virulence factor .

And here is a small list of some of the bacterial

virulence factor

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So in order to cause disease some bacteria contain one or

multiple of the following

We have tors that allow bacteria to adherence to host cell if

they can't adhere they can't cause disease

They can sometimes express factor or proteins that allow

them to invade inside host cell or invade tissue

They can also produce toxin

They can produce enzyme which usually are instructive

enzyme that allow them to destroyed the tissue.

They can produceAntiphagocytic factors that allow them

either to resist phagocytises all together ,,,, for example forthis .. capsule . That allow them to resist phagocytotic

killing So even if they get phagocytosis they will not be

killing.

Also some bacteria has specific factor that allow to survive

inside the host cell so basically becoming intracellular

pathogens.

And also they have factor to allow them to change the

antigenic structure in order to invade the immune system ..

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Also some virulent factor have relationship to human iron

levels

This allow them to be virulent inside human cell , inside

human body but not virulent outside .

And finally some bacteria can produce biofilm which

allow them to invade the immune system to resist the

antimicrobial drugs.

Slide 11 .

Here is a very short example

So some bacteria and viruses as we mention need to have

specific adhesions molecule under surface in order to bindwith specific receptor found in a specific host cell

So these are called (adherence ) Or ligand and they bind

specific receptor .And another example of adherence are

pili or the fimbiriae which we talked about it

previously ;and pili, one of the main function is which

allow the bacteria to attach the host cells surface ..

So these the infection of the viruses ..

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So the viruses has specific molecule in surface adheres or

ligand that recognize by specific receptor found in

specific host cell ..

So if this interaction happens this viruses can then inter

the cell and causes the disease in that cell .But cannot

cause disease on a host cells that doesnt have these

receptor on its surface ..

Slide 12 :

And this figure shows u basically some of the virulence

factor that are released or made by certain bacteria ..

As we mention

-pili : are the virulence factor because it allow attachment

- capsule : it considered to be a virulence factor because

it allow the cell to resist phagocytosis ..

- endotoxine : which is the lipopolysaccharide component

of the outer membrane of the gram negative bacteria .

Is considered to be a virulence factor because can

produce fever inside the host cell .

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- Some bacteria can produce exotoxine such as :

neurotoxins . enterotoxins and cytotoxins which have

a varaytoabrose inside the human body ..

- Some bacteria can produce coagulase which leads

to angulation or to position of fibrin around the

bacteria which allow them to invade the immune

system .

- Some bacteria can produce hemolysis and

leukocidrins that allow them to lyses RBCs and

WBCs .

- Some bacteria can produce collagenase and

( hayalnurinases ) which allow them to destroy

and basically digest human tissue to allow the

bacteria to spread more easily within the tissue .

- And finally some bacteria produce kinase.

So a virulence factor are basically phenotypic representation

of particular virulence genes

So many of the virulent genes will found to be carried

extra chromosomal genetic human such as plasmid ,,

however some bacterial chromosome may contain some

virulent genes , however if they found chromosome the

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virulence gene are usually group together in the area

called a pathogenicity islands (PALs)

So the (PALs) are large group of genes are associated with

pathogenicity and are located in the bacterial chromosome

For example in (PALs) :

genes for toxins, adhesions, lytic enzymes, antibiotic

resistance, and iron uptake.

So a very important question is is how the bacteria know

when to express the particular virulence factor??

The answer is very simple

- Bacteria are extremely adapted to their environments.- Bacterial genes are only expressed when required to

conserve energy.

- Virulence Genes are usually expressed upon entry into the

host.

And the question now how does the bacteria know that it

entered a host ??

So the bacteria are very cleaver it can sense the

changes around it

So it can sense the multiple signals such as :

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Changes in Temperature so in environment the temp.

Maybe 20C

But once inside the host the temp. Become 37 C

They can also sense Iron availability even though the

human body has a lots of Iron most of this iron is not free

format usually most of this for pump protein , so basically

bacteria can sense the slow level of free sulphating Iron

and then can express virulent factor

They can check sense changing of osmolarity ph and

concentration of specific ion such as (Ca2+ ) Or also can

detect the present or absence of nutrients

All these of the sensor can detect when they enter the host

and when they outer the host and therefore know when

express the virulent factor or when not

Examples:

- Corynebacterium diphtheriae (having the gene for the

diphtheria toxin) will only express the toxin when iron levels

are low. Such as inside the human body

Bordetellapertussis which causes Whooping cough or in

Arabic so this bacteria is produce or express

most of the virulence gene when the temp. Around 37C

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Slide 14

So after attachment , multiplication and spread some

bacteria can invade or inter the host cell and becomeintracellular pathogens and we have some example of this

we dont have to memorize it ..

Other bacteria do not become intracellular and they just

stay outside the cell but within the tissue and organ ..

So we called these basic or terminal invagenous tissue ex

( salmonella species )

So as the bacteria are growing and multiply and spreading

within the tissue some bacteria can produce one or two

type of the toxins

So we have something called :

Exotoxins can produce by gram +ve and ve bacteria and

we have different type of these

And we have another type of toxin and this is made only

by gram ve bacteria called endotoxin and specifically LPS

component of the cell wall

So the characteristic of these type of cytotoxin is very

important :

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Exotoxine : can made by Gram +ve and ve bacteria they

are highly toxic so very small amount of exotoxine can kill

the human so usually 1microgram of exotoxin can kill thehuman

These molecules are basically made up of protein so

protein are highly immunogenic inside the host so if u

get expose to an exotoxin agno-servived the toxin was

present in presentation for good amount of time the

immune system can produce antibodies against these toxin

Can neutralize the toxin and prevent them from functioning

inside the host ..

So in order to protect the human from exotoxin such as

(tetanospasmin and Diphtheria toxin Some receptor took

these toxins and treated them with formaldahide or

formaline .

If u do this side of treatment the toxic properties of the

toxin would be inoculated but its antigenisity will not change

..

So you can take this formaldahide in antibiotic toxin or

which equal toxoil and ejected inside the humans and that

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basically will protect them from exposure with really toxin

later in life

The composition of the exotoxin basically its made up of

two subunit :

We have a subunite called A (activity subunit ) has a toxic

activity of the toxine .. the A subunite is usually associated

with a B (Binding ) subunit and a B subunit allows the toxin

to attach to specific host cell

So examples of these toxin :

The Diphtheria toxin produce by C. Diphtheria this toxin

enter host cell and prevent cell protein synthesis leading to

cell death

tetanospasmin or tetanostoxin produce by (Clostridium

tetani):

for example if u puncture your foot or hand and become a

deep wound with a dirty instrument u will feeling that this

bacteria will produce tetanospasmin that prevent the muscle

from relaxing so all ur muscle will continue to be in an

Exciting contractive state ..

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so we have something called Spastic paralysis another

example is Botulinum toxin produce by Clostridium

botulinum

so this is a toxin that we found in a swelling cans food

..this bacteria make the swelling in cans and leading to

death

And finally we have Clostridium perfringens,, so these

bacteria found as a component of a normal flora of your

gastric intestinal tract

This bacteria is anaerobic so if u have a deep wound ( a

deep wound is required because it provides anaerobic

environment of the bacteria ) contain these bacteria it can

start growing and producing lots of toxin and enzymes that

destroy the tissue so end up basically of something called

Gas gangrene ;) ;) ;)

Due to the toxin and enzyme produce by this bacteria ..

And some toxin are called alpha toxin and theta toxin. And

these basically destroy RBCs and destroy lots of host

tissue ..

Slide 16 :

Endotoxins: so Endotoxins are basically Lipopolysaccharides

(LPS) of gram negative bacteria.

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So if u see an example asking u endotoxine can made by

gram +ve bacteria so the answer is no

Only gram ve bacteriaSo these LPS are usually released upon death or destroy

the cell so once the cell die the cell wall component will

diffuse away and it can end up with effect of endotoxin

and the important properties of endotoxin is the heat-stable

so if u have a solution and u want heat it the bacteria will

kill but the endotoxine will still be active .

so this is to constrict the exotoin which is heat lay bay so

if u boil food which contain the exotoxion we can destroy

the toxin

now LPS is composed of three main parts ::

O-specific polysaccharide and Common core polysaccharide

, lipid A and finally KDO so the structure within the LPS

that responsible for endotoxine properties is lipid A and

KDO

So general speaking that considered LPS as endotoxin but

if u want to be very accurate and specific lipid A and KDO

that responsible for primary toxicity of the endotoxine

So now how does the endotoxin work ..???

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The pathophisiology of endotoxine is regardless of the type

of the gram ve bacteria all endotoxine will function in the

same way once inside the circulation except of this rule

Bacteroides species this is gram negative bacteria found in

GI tract these have slightly deferent structure of LPS are

slightly less toxic than other type of LPS

So once u have LPS in bloodstream interact with receptor

found in microphages and monocytes and other cells of

the reticuloendothelial system need to release cytokines

most important cytokines is IL-1 which induce fever also we

have realise of Tubular Necrosis Factor (TNF) and other

Cytokines also we end up of activating the complement and

coagulation cascades so attractive of all these will introduce

fever so end up also we end up of hypotension and shock

and these invention will end up with more serious problem

impaired blood flow to essential organs (e.g, brain, heart,

kidney. the activation of coagulation; cascade will lead to

intravascular coagulation; and death from massive organ

failure or dysfunction

Now the important virulence are enzyme such as exo-

enzymes

Examples:

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- C. perfringensproduces two toxin alpha interotoxin it can

also produce a lecithinase and a collagenase that degrade

tissues thus promotingbacterial spread inside the tissues

-Staph. Aureusif enters the blood it will use its enzyme

called a coagulase to clot of plasma and formation of fibrin

forming a shell of fibrin to hide bacteria from the immune

system and thus protect the bacteria from phagocytosis ..

Also other enzymes that can destroy the cell for example

hemolysis can lyses or destroy RBCs also some cytolysins

can produce kill typical host cells and some cytolysis called

leukocidins) are produce specifically to kill WBCs

(leukocytis)

EX Streptolysin O produce by group A streptococci such

as streptocoocus phygens this one can destroy RBCs of

human and other animals as mice

So the key point when ether we talked about virulence

factor or virulence mechanism in pathogens is The major

mechanisms by which

pathogens cause disease are the exoenzymes or toxins that

they produce.

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So as we mention some bacteria have a virulence

mechanism that can allow them to either evade

phagocytosis or avoid the killing of phagosomes and the

base example of this Polysaccharide capsules ofS.

pneumoniae, and N.meningitidis.

The next intracellular factor is Intracellular Pathogenicity:

Intracellular Pathogenicity: have a virulence factor that allow

them to survive inside the host cells

Example of intracellular bacteria is:

- Mycobacterium tuberculosis that cause human tuberculosis

Antigenic Heterogeneity so as we now if u introduce an

organism in a host the immune system will respond to

that pathogen and will produce antibody against cell.

So in theory if u get expose to one pathogen u should be

able to prevent infection in second time of the same

pathogen but many bacteria and many other pathogens

have a ways to keep changing there surface antigens that

are immunogenic inside the host cells

So Bacteria have three types ofsurface antigens That the

immune system pathogens respond to :

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O antigen which is part of LPS of gram ve bacteria so

these antigens only present in gram ve bacteria

Bacteria that have flagella that able to move so motile

bacteria have antigens in their flagella structure called F

antigens

And bacteria that contain a capsule will have capsule

Antigens called K antigen

So if u get expose for example to E. Coli have an O

antigen type 7 your body will respond to this antigen by

produce neutralizing antibodies and if u get expose of E.coli

O type 7 second time in future u will protective but E.coli

can perform many types of O Antigen

So if u get expose of E.coli O1 after O7 we will infected

again because that Antibodies is only specific for O7 not

O1

So in the environment e.coli has up to150 or more types

for its O antigen and has more than 100 types for

capsular or K Antigen

So that is why u can infected with E.coli time and time

again

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Most likely u get infected with E.coli carried with different

type of antigens

In addition to this some bacteria will actively change the

antigen while inside the host so even as a immune system

is recognize this antigen this antigen are changing over time

For example : N. Gonorrhoeae and Borrelia recurrentis

which (causes relapsing fever can make frequent changes

in their surface antigens

to evade the immune system.

Finally ..

The last virulence factor is Ability to form Biofilms:

So basically bacteria not always present as single cell in

the environment some bacteria have basically develop high

order structures called biofilms

So biofilms are aggregate or accumulation of interactive

bacteria usually attached to a solid surface or to each other

and encased in an exopolysaccharide matrix

so basically bacteria can grow forming a large mass and

then will secret some type of polysaccharide covering or

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layer around them protect them from the outside

environment so this called a biofilm

Biofilms basically are a slimy coat found on solid

surfaces and

occur throughout nature.

So what is the significance of biofilms in pathogensis and

the ability to bacteria to cause disease

So biofilms by having that polysaccharide capsule around

them allow the bacteria to give protected from the

immune system so immune cells cannot penetrate and go

inside the bacteria also that covering or layer will not to

allow most trubile agent to pass through and kill the

bacteria so medically speaking we will count the biofilm in

narrower examples

Staphylococcus epidermidis and Staphylococcus aureus

which are found in as normal flora of the epidermal skin

can contaminate catheters ex >> central

venous catheters can follow by this bacteria and this

bacteria will grow form a biofilm that is very hard to

remove leading to bide infection inside the host

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also people who work contact lenses has an eye infection

because some bacteria produce biofilms or contact lenses

and also dental plaque some of plaque involve the

formation of biofilms by bacteria within the plaque ..

also the virulent example is .people with cystic fibrosis they

had usually a problem with Pseudomonas aeruginosa

which can form a biofilms that are very hard to remove and

anon easily clear by trouble agent

sorry for any mistake ,

Done BY :

SARA ALOMARI

Special thx to my lovely Friends (RUBA RABE,,, DALIA

SHUNAQ ,,, YASMIN ABU ZAID )


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PLZ Forgive me if there is mistakes i really do the best ..

GOOD LUCK ...

.

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Documents

Microbiology, Lecture 14+15