This document summarizes the mechanisms of pathogenesis for microbes. It discusses the key steps microbes use to cause disease: entry through portals like mucous membranes or skin, adherence to host cells, penetration of host defenses, and damage through nutrient acquisition, direct invasion, or toxin production. Specific virulence factors like capsules, cell wall components, exoenzymes, and antigen variation are described. The differences between exotoxins and endotoxins in their modes of action and impacts on hosts are also highlighted.

1. Microbiology
chapter 15
Microbial Mechanism of
Pathogenecity
Done by:
farah el soheil

2. Steps to cause a disease
➢ Entry
➢ Adherence
➢ Penetration (evasion of th immune system)
➢ Damage ( direct or indirect )
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3. i) Entrance
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4. Portals of entry
●
Mucus membranes
( RT,GIT,GUT,conjunctiva)
●
Skin ( through hair follicles or sweat
glands)
●
Parentral rout ( direct depostion under
skin , microbe enter through
wound,cuts,grazes .. which is not always
present)
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5. microbes that enter through Mucus Membranes
●
Most pathogens enter though the mucus membranes especially
the RT.
–
RT: easiest and most frequent
dx: common cold, pneumonia, tb, influenza, measles, smallpox
transmission: inhaled into mouth or nose in dust or moisture.
–
GIT: the microbe in its way faces Hcl, enzymes of stomach, bile, and
enzymes of small bowel.
Dx:poliomyelitis, hepatitis A, typhoid enteric fever, amoebic desentry, giardiasis,
shigellosis(bacillary desentry), cholera.
Transmission: fingers, water, food
elimination : through feces
–
GUT: the most common reported STD is chlamydia
dx: HIV,genital warts (herpes), syphillis, gonorrhea,
–
Conjunctiva: which forms an effective barrier but microbes can still pass
dx: conjunctivitis , trachoma, ophthalmia neonatrum.
N.B: STD can enter though parentral route or GUT Farah el soheil

6. *Microbes that enter through parentral route
●
Directly deposited into tissues beneath skin
or into mucus membranes when these
barriers are penetrated or injured.
Ex: puncture, injection,
bite,cut,wound,surgery, split in skin or mucus
membrane due to swelling or drying.
Dx: HIV, hepatitis, tetanus, gangrene.
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7. Prefered portal of entry
●
Occurrence of dx depend on a prerequisite
which is by which portal of entry it's pathogenic,
so that if it gains entrance to other routes it may
not be pathogenic.
●
Ex: salmonella cause dx when its swallowed not
by skin.
●
s. pneumonia : causes disease when it's inhaled
not when swallowed.
●
Some microbes can cause dx by more than one
route ( yersenia pestis which causes plague,
bacillus anthracis : skin, RT , parentral )
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8. Nb of invading bacteria
●
If small then its overwhelmed by the host defense.
●
Likelihood of disease increase as number of pathogens
increase.
●
Virulence is compared by ID50 which Is the dose that
causes infection in 50% of population. So, as the most
virulent is the microbe with smallest ID50.
●
ID50 decrease if barriers are removed.
●
Potency is compared by the LD50 which is the lethal
dose in 50% of population.
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9. ii)Adherence
●
Necessary step in pathogenecity, almost all microbes have it but that doesn't
mean that non-pathogens don't have attachment sites.
●
Factors:
–
On pathogen: adhesin/ligand (glycoprotein or lipoprotein) which is located on glycocalyx,
pili, fimrae, falgella. Such adhesins differ even between different strains.
–
On host cell : complementary receptor(sugar: mannose) which differ between different cells
of the host.
●
Thus, to avoid infection we can alter either th eadhesins or receptors
●
Ex: adhesions of :
–
Actinomyces, N.gonorrhea, EPEC are on fimbrae
–
S. mutans are on ( glycocalyx which is made up of dextran sugar derived from glucose)
●
Receptors of N gonorrhea are on eye , pharynx, GUT.
●
Syphillis use its tapered end to attach
●
Shigella and Ecoli multiply within host cell.
●
Biofilms: group of microbes and extracellular product that can attach to living and
non living surfaces ( on one condition that its moist and has organic molecules). It
may contain several types of microbes but bacteria is the first to attach.
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10. iii) Penetration
●
Not a determining step but the majority of microbes penetrate
host cell, others let their toxin penetrate.
●
After adhesion the bacteria prodices invasin that causes
changes in PM at point of contact ( rearrangement of actin
filaments of cytoskeleton).
●
Actin protein is also used by the bacteria to move through cell
and from one to another
●
Ex of changes is the membrane ruffling ( wave like motion )then
the microbe sinks into ruffleand its engulfedby host cell
●
Bacteria use cadherin to move from cell to cell ( bridge the
junction made by the actin filaments)
●
Shigella and lysteria move from cell to cell.
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11. Virulence factors
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12. A- Capsule
●
Which maybe glucocalyx if firmly bound or slime layer if loosely
bound.
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It inhibits adherence of immune cells and resist phagocytosis
●
Nonpathogens may have capsule.
●
Antibiotics that work on capsule are formulated. So that it's asily
destroyed if it's uncapsulated.
●
Ex:
–
S.pneumonia (pneumonocal pneumonia)
–
Klebsiella pneumonia (bacterial pneumonia)
–
Hemophillus influena
–
Bacillus anthracis (Anthrax)
–
yersenia pestis ( plague)
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13. B- cell wall components
●
M protein: heat and acid resistant protein it may be
present on cell surface or fimbrae and it helps the
microbe attach to ep cells and resist phagocytosis.
There's an Ab that work on M protein. ( s.pyogen)
●
Opa protein which cause the formation of opague
colonies on culture.(n.gonorrhea)
●
Fimbrae: attachment site
●
Mycolic acid ( waxy lipid ) : resist phagocytosis
(tuberculosis)
●
Tb and n. gonorrhea can multiply in wbc
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14. c- exoenzymes ( extracellular)
●
Coagulase ( s.aureus) :coagulate fibrinogen in blood to fibrin clot so
it protects bacteria from phagocytsis.
●
Bacterial kinase:digest clot made by the body to isolate infection but
this enzyme ,not the bacteria itself, can be used in Tx of obtsructed
coronary artery. ( helps microbe spread in blood)
–
Fibrinolysin ( streptokinase) : (S. pyogen)
–
Staphylokinase ( S. aureus )
●
Hyaluronidase:( streptococcus and clostrdium perfirenges) : it
hydrolyzes hyaluronic acid ( polysaccharide) that hold cells of CT. it
leads to tissue blackening of infected wounds. It helps bacteria
spread from site of infection through tissues. . The enzyme is also
used in medicine to help the drug to spread .
●
Collaginase: it breaks down collagen and fascilitates the spread of
gas gangrene produced by C.perferenges through tissues.
●
IgA protease: (neisseriaand the microbes that infect CNS) it destroy
IgA Ab made to inhibit adherence.
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15. D- Ag variation
●
Pathogen that alter their surface Ag so
that by the time the body mounts an
immune response the pathogen will have
had altered its Ag by activating alternative
gene ( it initially has several copies of a
gene)
●
Ex: N.gonorrhea salmonella and influenza
virus.
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16. iv) damage
●
Ways:
–
Use host nutrient: siderophore
–
Direct damage in vicinity of invasion
–
Produce toxins transported by blood and
lymph so that it damages sites from the
original site of invasion.
–
Induce hypersenitivity reaction.
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17. 1- Usage of nutrients
●
Free iron in body is low most are in complex form.to
obtain iron the microbe uses one of 3 ways:
–
Release Siderophore: protein secreted by microbe and it binds
to iron more tightly. And there is a siderophore receptor on the
bacterial surface. Then either the iron alone or the complec
enters.
–
Have receptors for iron transport proteins and hemoglobinon
the bacterial surface. Then the whole complex in engulfed.
–
Release toxins that kill host cells when iron is low and release
their iron in the free form.
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18. 2- Direct damage
●
Pathogens multiply in host cell using host cell
nutrients and accumulation of wastes which causes
the cell to rupture and the intracellular bacteria,
protozoa, virus are released and spread in greater
nb.
●
Ex: e coli, N. gonorrhea,salmonella,shigella that
induce their own engulfment by process similar to
phagocytosis
●
Other microbes can penetrate cell by secreting
enzymes ot their own motility. Such penetration can
damage host cell.
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19. 3- Production of toxin ( endo or exotoxin)
●
Most common way of damage
●
It's the primary factor contributing to pathogenicity of microbe.
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Toxigenicity: ability to produce toxins
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Toxemia: toxins in blood
●
Fatal if toxin is trasported by blood or lymph
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Effect:
–
Fever, CV disturbance, diarrhea, shock.
–
Inhibit protein synthesis.
–
Destroy blood cells or BV
–
Disrupt nervous system by causing spasm
–
Damage eukaryote PM.
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20. A- exotoxin
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Produced inside bacteria
●
Secreted / released following lysis
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Protein( enzyme mostly ) so that small qty is harmful
●
Produced by both gram + ( mostly) and -
●
Gene is carried omn plasmid
●
Soluble in bodily fluids so it can easily spread inside the body.
●
MOA: destroy particular part of the host cell or inhibit certsin metabolic
functions.
●
Most lethal ( low LD50)
●
Highly specific
●
Signs and symtoms are disease specific
●
Antitoxins are effective
●
Vaccines are present ( attenuated protein called toxoid)
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21. A- exotoxin
●
Naming According to:
–
host cell :
●
Cardiotoxin,neurotoxin,hepatotoxin,leukotoxin,
enterotoxin(GIT),cytotoxin( attack wide variety of
cells)
–
Dx they cause:
●
Diphtheria toxin, tetanus toxin.
–
Bacteria that produce them:
●
Botulinium toxin , vibrioenterotoxin.
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22. A- exotoxin
●
Types:
–
A-B toxin:
●
A : active enzyme
●
B : binding
●
A-b is first released from bacteria
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B attach to host cell receptor
●
PM invaginate at pt of contact an dthe exotoxin enter by
endocytosis.
●
A-B exotoxin and receptro are enclosed
●
A and b separate A alter the function of the host ( inhibit
protein synthesis) ,B is released from host cell and the
receptor is inserted in PM for reuse.
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23. A- exotoxin
–
Membrane disrupting :
●
Lyse host cell by disrupting PM by :
–
Forming protein channels in PM
–
Disrupting phospholipid portions
●
Virulence: It can kill host cell or escape phagocytosis
●
Toxin that kill :
–
Leukocyte : ( by forming protein channels) is called leukocidin and
it's produced by Staph and strep.
–
Erythrocyte :( by forming protein channels) is called hemolysin
●
One type is streptolysin which lyse both RBC and WBC
produced by strep which has 2 forms:
●
Streptolysin O : destroyed by oxygen
●
Streptolysin S : stable in presence of oxygen
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24. A- exotoxin
–
Super antigen:
●
Ag are proteins that provoke very intense immune
response by stimulating production of T-cells
●
Enormous amounts of cytokines ( protein that regulate IR
and mediate cell to cell communication
●
It produces symptoms : fever nausea vomiting diarrhea

25. exotoxin Type mode of action
Diphtheria toxin A-B Cytotoxin inhibits protein synthesis
Erythrogenic toxin Super Ag By S pyogen it damages the PM of
blood capillaries and causes scarlet
fever
Botulinium toxin
Tetanus toxin
A-B neurotoxin Acts at NMJ and inhibits the
transmision nerve impulse by
inhibiting the release of
Acetylcholine so it causes flaccid
paralysis ( lack of muscle tone)
Tetanus toxin Tetanospasmin A-B
neurotoxin
Binds to neuron that normally
prevent random contractions and
terminate completed contractions so
it blocks relaxation and causes
spasmotic contractions “lock jaw”
vibrioenterotoxin A-B cholera toxin B part binds to ep cell and A part
causes the intestinal cell to secrete
large amounts of water and
electrolytes so it causes diarrhea
Staph enterotoxin Super Ag Same as vibrioenterotoxin

26. B- endotoxin
●
It's a part of the outer portion of cell wall of gram
(-) lipid portion of LPS called lipid A
●
Endotoxins are LPS not proteins
●
Released when the cell dies and the cell wall is
lysed and during bacterial multiplicaion
●
Treatment may worsen the case and symptoms
appear but the condition improves then after the
endotoxin breakdown.
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27. B- endotoxin
●
Stimulates macrophages to release cytokines in high concentration
–
All endotoxins produce same signs regardless of the infecting microorganism : chills
fever weakness aches shock miscarriage
●
It activates blood clotting proteins so capillary obstruction follows (DIC:
dissiminated IV coag.)
●
The gram (-) ingested by phagocyte then the bacteria is degraded in vacuoles
and the LPS is released. The amount of cytokines (IL1 and TNF) in blood
then increaeses and they are transported to the hypothalamus which is
stimulated to release prostaglandin and the hypothalamus is reset at a higher
temperature which causes fever
●
ASA and acetaminophen decrease fever by inhibiting syn of PRG
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28. Notes
●
Shock types :
–
Septic : decrease in BP and is caused by
bacteria
–
Endotoxin by gram (-) due to cytokines(TNF)
by macrophages which binds to many tissues
in the body and alter their function and
damage blood capillaries → permeability
increase → fluid loss → BP decrease
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29. Notes
●
No effective antitoxin against
carbohydrate component of endotoxin,
Antibodies are produced they may
enhance the effect but still are not
effective as those against the exotoxin
●
LAL: procedure that indicate the presence
of endotoxin. If the gel clots then the test
is (+)
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30. Good luck