Microbiology

chapter 15
Microbial Mechanism of Pathogenecity

Done by:
farah el soheil

Steps to cause a disease

Entry

Adherence

Penetration (evasion of th immune system)

Damage ( direct or indirect )

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i) Entrance

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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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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, smallpoxtransmission: 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, foodelimination : through feces

GUT: the most common reported STD is chlamydiadx: HIV,genital warts (herpes), syphillis, gonorrhea,

Conjunctiva: which forms an effective barrier but microbes can still passdx: conjunctivitis , trachoma, ophthalmia neonatrum.

N.B: STD can enter though parentral route or GUT

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*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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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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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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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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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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Virulence factors

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A- Capsule

Which maybe glucocalyx if firmly bound or slime layer if loosely bound.

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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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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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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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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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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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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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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3- Production of toxin ( endo or exotoxin)

Most common way of damage

It's the primary factor contributing to pathogenicity of microbe.

Toxigenicity: ability to produce toxins

Toxemia: toxins in blood

Fatal if toxin is trasported by blood or lymph

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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A- exotoxin

Produced inside bacteria

Secreted / released following lysis

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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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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A- exotoxin

Types: A-B toxin: A : active enzyme

B : binding

A-b is first released from bacteria

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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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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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

exotoxinType mode of action

Diphtheria toxinA-BCytotoxin inhibits protein synthesis

Erythrogenic toxinSuper AgBy S pyogen it damages the PM of blood capillaries and causes scarlet fever

Botulinium toxinTetanus toxinA-B neurotoxinActs at NMJ and inhibits the transmision nerve impulse by inhibiting the release of Acetylcholine so it causes flaccid paralysis ( lack of muscle tone)

Tetanus toxinTetanospasmin A-B neurotoxinBinds to neuron that normally prevent random contractions and terminate completed contractions so it blocks relaxation and causes spasmotic contractions lock jaw

vibrioenterotoxinA-B cholera toxinB 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 enterotoxinSuper AgSame as vibrioenterotoxin

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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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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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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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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Good luck