Chapter 15: Microbial Mechanisms of pathogenicity

• Pathogen = microbe or virus able to produce disease

• Pathogenicity = the ability of a microbe to cause disease in another organism– Ex. The host – usually human

• Virulence = the power of an organism to cause disease– It is the degree of pathogenicity– Virulent organisms usually produce a violent, severe

disease often leading to death

Chapter 15: Microbial Mechanisms of pathogenicity

• Virulence cont. – Chickenpox, common cold viruses are

pathogens not considered to be virulent– Yersinia pestis – bubonic plague, Ebola

viruses – virulent pathogens

• Virulence factors = pathogen produced molecules or structures that allow the cell to invade the host or evade your immune system and may result in disease in the host

How do microbes become established in a host

Step 1

• Portal of entry – how pathogens get in or onto the body– Mucous membranes – line the conjunctiva of

the eye, and the respiratory, Gastrointestinal and genital -urinary tracts

• Respiratory tract is easiest and most frequently used route – cold, pneumonia, TB, flu, measles, smallpox

How do microbes become established in a host

• Step1:Portal of entry: Mucous membranes– Gastrointestinal tract – contacted through

food, water, fingers• May be destroyed by stomach acids and intestinal

enzymes• Ex. Polio, hepatitis A, typhoid fever, amoebic

dysentery, shigellosis (aka bacilliary dysentery), and cholera are transmitted through the GI tract

– Pathogens leave (Portal of exit) through the feces to find a new host

How do microbes become established in a host

Step 1: Portal of entry : Skin

• Most microbes can’t penetrate unbroken skin– Some can penetrate by entering through

openings – hair follicles, sweat ducts– Fungi can grow in the keratin of the skin and

infect the skin or nails– Exception to unbroken skin is hookworms

How do microbes become established in a host

• Step 1: Portal of entry : Parenteral route– Microbes enter due to trauma to the skin and mucous

membranes– Ex. Injections, punctures (tetanus), bites, cuts,

wounds, or surgery

• Microbes must enter your body from the preferred portal of entry to cause the disease– Ex. Smallpox – mucous membrane of respiratory

tract, thru puncture of skin = slight inflammation of skin – immunity, vaccination

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ntry “Many

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one disease if they enter

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another, e.g., various enteric

urinary-tract pathogens.

How do microbes become established in a host

• The ability of a pathogen to establish an infection and possible disease usually depends on the infectious dose which is the # of microbes taken into the body

• A measure of virulence is the ID50 (infectious dose) = the number of microbes it takes to infect 50% of the population– Cutaneous anthrax ID50 = 10 endospores, inhalation

anthrax ID50 = 10,000 endospores

• The potency of a toxin is the LD50 or lethal dose to kill 50 % of a population

How do microbes become established in a host

• Step 2: Adherence or attaching to the host– Pathogens attach to host cells by adhesins

which are projections on the surface of the bacterium that adhere to complimentary receptors on the host cells

– Adhesions are associated with fimbriae, glycocalyx, flagella

– Parasitic worms use hooks, barbs, suckers

How do microbes become established in a host

Step 2: Adherence• Adherence is followed by colonization of the

tissue and may involve invasion of the cells

Ex. Biofilms – microbes secrete a glycocalyx that aids in surface attachment and to each other

• This allows them to share nutrients, and they are protected from antimicrobials and your immune system ex. Diphtheria –Corynebacterium diphtheriae

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For most pathogens, cells must adhere to tissues (and then colonize) before infection can take place, even if ultimately damage results from invasion or exotoxin production.

Bacteria typically employ proteins known as Adhesins to attach to host tissues, which usually are located on ends of fimbriae.

Alternatively, adhesins can consist of glycocalyx.

Step 3: Penetrating and surviving host defenses

• Capsules – aid in resistance to phagocytosis

– Streptococcus pneumoniae causes pneumococcal pneumonia – some strains have capsules and are therefore virulent and produce disease and some strains don’t have capsules and are avirulent and don’t cause disease

Avoidance of Phagocytosis

Capsules are Involved in avoidance of

phagocyte-mediated recognition and

attachment.

Step 3: Penetrating and surviving host defenses

• Cell wall components – aid in resisting phagocytosis and in adherence of microbes– Waxes in cell wall – Mycobacterium

tuberculosis resist digestion by macrophages– M protein produced by Streptococcus

pyogenes aids in attachment to epithelial cells and resistance to phagocytosis by WBCs

Step 3: Penetrating and surviving host defenses

• Enzymes – extracellular enzymes are able to lyse cells, dissolve the material between cells and form or dissolve blood clots– Coagulases – enzymes produced by some

Staphylococcus – converts fibrinogen to fibrin which causes clotting – the clots protect against phagocytosis

Step 3: Penetrating and surviving host defenses

– Kinases – Staphylococcus and Streptococcus – digests the fibrin thus dissolving the clots formed by the body to isolate the infection

• Streptokinase – used to remove some blood clots due to heart attack

– Hyaluronidase –Streptococcus, Staphylococcus, Clostridium – digests hyaluronic acid of connective tissue

Step 3: Penetrating and surviving host defenses

– Collagenase – Clostridium sp. – dissolves collagen framework of muscles – aids in the spread of gas gangrene

– IgA proteases – destroys host’s defense IgA antibodies

Antigenic variation – microbes are able to change their surface antigens ( causes Ab formation)

- the immune system recognizes antigens (pathogens) and produces Abs specific for that Ag

How Pathogens cause disease or damage

• Using the hosts nutrients – pathogens need iron to grow– Iron in the host’s cell is tightly bound to iron transport

proteins such as hemoglobin– Some microbes secrete proteins called siderophores

which take the iron away from the iron transport proteins and form iron – siderophore complexes. These complexes bind with siderophores receptors on the bacterial surface where the iron is brought into the bacterium either as the whole complex or free iron

– Cell lysis caused by pathogens can also release iron

How Pathogens cause disease or damage

• Toxins – are poisonous substances produced by some microbes. If toxins are found in the blood = toxemia

• Exotoxins are proteins usually secreted by Gram + bacteria– They are among the most lethal substances

known– They are specific to a cell type ex. Neurotoxin

How Pathogens cause disease or damage

• Exotoxins cont.– The body can produce Abs called antitoxins

that provide immunity to exotoxins– Toxoids are altered exotoxins that allow the

host immune system to produce antitoxins without causing any side effects

• Can be vaccines ex. Diphtheria, tetanus

How Pathogens cause disease or damage

• Types of exotoxins– A-B toxins – most are exotoxins, consists of 2 parts

• A is the active part that inhibits protein synthesis and kills the host cell

• Part B is the binding part and binds to host cell

– Membrane disrupting toxins – cause lysis of host cells by disrupting their plasma membranes

• Leukocidins – white blood cell killers• Hemolysins – target red blood cells

How Pathogens cause disease or damage

• Types of exotoxins cont.– Superantigens – provoke an intense immune

response• Stimulate the proliferation of T cells which in turn

release large amounts of cytokines• Cytokines are small proteins that regulate immune

responses and in high concentrations can cause many sxs – fever, nausea, vomiting, diarrhea, shock and even death

How Pathogens cause disease or damage

• Some exotoxins– Diphtheria toxin – Corynebacterium

diphtheriae – A-B toxin, bacteria has to be infected by lysogenic phage (prophage) carrying the tox gene

– Erythrogenic toxin- Streptococcus pyogenes –is a superantigen that damages plasma membranes of capillaries under the skin and produces red skin rash ex. Scarlet fever

How Pathogens cause disease or damage

• Some exotoxins cont.– Botulinum toxin – Clostridium botulinum –

A-B neurotoxin that causes flaccid paralysis when ingested

-- Tetanus toxin – Clostridium tetani – A-B neurotoxin aka tetanospasmin which blocks the relaxation pathway of muscle control causing spasmodic contraction = tetanus ex. Lockjaw-mouth, opisthotonos – back mspg.648 fig. 22.6

How Pathogens cause disease or damage

• Some exotoxins cont– Vibrio enterotoxin – Vibrio cholerae –A-B

enterotoxin (aka cholera toxin) that causes the release of large amounts of fluids and electrolytes (ions) that result in severe diarrhea ex. Cholera

– Staphylococcus enterotoxin – S. aureus – superantigen that affects the intestines the same way as cholera toxin

How Pathogens cause disease or damage

• Endotoxins = lipid A which is the lipid portion of LPS (outer membrane) of G- cell wall– Not secreted but is released upon death and lysis of

the bacteria or during multiplication of bacteria– They stimulate macrophages to release large

amounts of cytokines which are toxic at high concentrations

– Lab test for endotoxins = Limulus amoebocyte lysate (LAL) assay

• Uses WBCs (amoebocytes) of horseshoe crab (Limulus polyphemus) which lyse if endotoxins are present releasing a clotting protein

• Draw chart

Pathogenic Properties of Viruses

• Cytopathic Effects (CPE) = visible damage to host cell– Cytocidal effects kill the cell– Noncytocidal effects damage cell – not lethal

• A virus can produce one or more of the following CPE– Stops the synthesis of macromolecules– Cause cell’s lysosomes to release their

enzymes and lyse themselves

• CPE cont. pg 466– Inclusion bodies = granules found in the

cytoplasm (rabies virus) or nucleus (herpes virus) if some infected cells

– Syncytium = adjacent infected cells fuse to form a multinucleated cell

– Change in fx but otherwise no visible change ex. Decreased hormone production

– Cell produces interferon which protects neighboring, uninfected cells from the virus

Pathogenic Properties of Viruses

• CPE cont.– Antigenic changes on the surface of infected

cells that target the cells for destruction by the immune system

– Chromosomal changes in the host cell, oncogenes may be activated

– Cancer causing viruses transform host cells resulting in abnormal cell shape and a loss of contact inhibition which causes unregulated cell growth

Pathogenic properties of fungi, protozoa, helminths and algae

• Protozoa and helminths grow on host tissues causing cellular damage– Their waste products may contribute to sxs of

disease

• Algae (dinoflagellates) produce neurotoxins called saxitoxin and people become ill after eating mollusks that feed on the algae

Pathogenic properties of fungi, protozoa, helminths and algae

• The toxin ergot is associated with some fungi and cause ergotism which can result in LSD type hallucinations– Ergot is contained in resistant mycelia called

sclerotia in Claviceps purpurea – fungi that grow on grains

– Ergot can constrict blood capillaries and cause gangrene in extremities

Pathogenic properties of fungi, protozoa, helminths and algae

• Aflatoxin is produced by the mold Aspergillus flavus and can cause cancer in the liver of animals

• Amanita phalloides (deathcap) is a toxic mushroom which contains the mycotoxins phalloidin and amanitin. – These neurotoxins are so potent that

ingestion may cause death

Portals of exit

• To complete the cycle of infectious disease and to allow transmission to new hosts, pathogens require a portal of exit

• In some cases the portal of exit relates to the area of the body infected

• Infections of the respiratory tract pathogens exit through the nose (sneezing) or mouth (coughing)

• Pathogens of GI tract exit – saliva, feces• Pathogens of genitourinary tract exit - secretions