Fat2.chapter15 (pathogenicity)

Microbiology

B.E Pruitt & Jane J. Stein

AN INTRODUCTIONEIGHTH EDITION

TORTORA • FUNKE • CASE

Chapter 15Microbial Mechanisms of Pathogenicity

Microbial Mechanisms of Pathogenicity

• Pathogenicity The ability to cause disease

• Virulence The extent of pathogenicity

~when a microbe overpowers the hosts defenses, disease results~

They need to gain entry, adhere, penetrate and cause damage to cause disease.

Disease: Pathogens may cause damage to host

• Direct damage in the immediate vicinity

• Grow and multiply and clog cells and passageways

• Far removed from site of invasion by toxins

• Toxins spread through blood and lymph

• By hypersensitivity

• The host’s reaction may cause the damage

Portals of Entry• Mucous membranes

• Respiratory tract

• Gastrointestinal tract

• Genitourinary tract

• Conjunctiva

• Skin• Tough so rare - Necator americanus - hookworm

• Parenteral route• Puncture, injection, bites, cuts, wounds, surgery, etc

How microorganisms enter a host?

1st Portal of Entry :Mucous Membranes -Respiratory

• Respiratory Tract

• microbes inhaled into mouth or nose in droplets of moisture or dust particles

• Easiest and most frequently traveled portal of entry

• Common cold

• Flu

• Tuberculosis

• Whooping cough

• Pneumonia

• Measles

• Strep Throat

• Diphtheria

Mucous membranes: G.I. Tract

• Salmonellosis

• Salmonella sp.

• Shigellosis

• Shigella sp.

• Cholera

• Vibrio cholorea

• Ulcers

• Helicobacter pylori

• Botulism

• Clostridium botulinum

Fecal - Oral Diseases

• These pathogens enter the G.I. Tract at one end and exit at the other end.

• Spread by contaminated hands & fingers or contaminated food & water

• Poor personal hygiene.

Mucous Membranes of the Genitourinary System - STD’s

Gonorrhea

Neisseria gonorrhoeae

Syphilis

Treponema pallidum

Chlamydia

Chlamydia trachomatis

HIV

Herpes Simplex II

Mucous Membranes: Conjunctiva

• Conjunctiva

• mucous membranes that cover the eyeball and lines the eyelid

Trachoma --------------• Chlamydia trachomatis

2nd Portal of Entry: Skin

• Skin - the largest organ of the body. When unbroken is an effective barrier for most microorganisms.

• Some microbes can gain entrance thru openings in the skin: hair follicles and sweat glands

3rd Portal of Entry: Parenteral

Microorganisms are deposited into the tissues below the skin or mucous membranes

• Punctures

• injections

• bites

• scratches

• surgery

• splitting of skin due to swelling or dryness

Preferred Portal of Entry

~ Just because a pathogen enters your body it does not mean it’s going to cause disease~

• Pathogens - preferred portal of entry

• Small pox via variolation

• Streptococcus pneumoniae

• if inhaled can cause pneumonia

• if enters the G.I. Tract, no disease

• Salmonella typhi

• if enters the G.I. Tract can cause Typhoid Fever

• if on skin, no disease

• ID50: Infectious dose for 50% of the test population

- virulence of pathogens

• LD50: Lethal dose (of a toxin) for 50% of the test population

- potency of toxin

Numbers of Invading Microbes

~ the probability of disease increases as the number of pathogens increases ~

ID50 for Bacillus anthracis

Portal of entry ID50

Skin 10 - 50 endospores

Inhalation 10,000-20,000 endospores

Ingestion 250,000-1,000,000 endospores

Key traits to a pathogen

The ability to:

• 1. Adherence

• To host surfaces and not be washed off

• 2. Avoid phagocytosis

• Prevent host defenses from destroying

• 3. Penetrate

• Get into host and spread

• 4. Produce Enzymes

• Spread, prevent host defenses and cause damage at or near site of infection

• 5. Produce Toxins

• Cause damage at distant site

Adhesins or ligands

• – surface molecules on the pathogen that binds specifically to complementary surface RECEPTORS of host cells.

• - located in glycocalyx, pili, fimbrae, flagella

Biofilms – another method of adherence

- communities which constitute masses of microbes & their extracellular products that can attach to living & nonliving surfaces

Examples:

> dental plaque of teeth

> algae on walls of swimming pools

> scum on shower walls

Adherence

Mechanisms of adhesion of some pathogens:

• Streptococcus mutans, a major cause of tooth decay, attaches to the surface of the teeth by means of its glycocalyx. Next, Actinomyces uses its fimbriae to attach to the glycocalyx of S. mutans. (biofilm)

• Pathogenic strains of Escherichia coli have adhesins or fimbriae that adhere to cells in certain regions of the small intestine. E. coli and Shigella cause host cells to take them in by endocytosis and then multiply inside them. 

• Treponema pallidum hooks its tapered end into a host cell.

• Listeria monocytogenes produces an adhesin for specific receptors on host cells.

• Neisseria gonorrhoeae also has fimbriae with adhesins which fit receptors of cells in the genitourinary tract, eyes, and pharynx.

• Staphylococcus aureus binds to skin cells in a mechanism similar to that of viruses.

Adherence

How bacterial pathogens penetrate host defenses?

Factors contribute to the ability of bacteria to invade a host:

Capsules

Enzymes

Antigenic variation

Penetration into the host cell cytoskeleton

Capsules

Resist the host’s defenses by impairing phagocytosis

Chemical substances of capsules that contribute to virulence:

M protein – heat resistant & acid-resistant protein

- mediates attachment of bacterium to epithelial cells of the host & helps bacterium resist phagocytosis by white blood cells

ex. Streptococcus pyogenes

Opa – outer membrane protein; together with fimbrae attach to host cells

ex. Neisseria gonorrhea – grows in human epithelial cells & leukocytes

Waxes – resist digestion by phagocytes

ex. ex. Mycobacterium tuberculosis

• Increase virulence by use of enzymes

• And avoid phagocytosis

Bacterial Enzymes

Coagulase Coagulate the fibrinogen in blood Kinases Break down fibrin and dissolve blood

clots formed by the body to isolate infection

streptokinase and staphylolinase

Hyaluronidase Breaks down polysaccharide that

holds together connective tissue

Collagenase Hydrolyzes protein collagen

IgA proteases Destroy IgA antibodies

Hemolysins Lyses RBC’s

Enzymes

Antigenic Variation

• Process in which a pathogen alter their surface antigens to avoid host antibodies

Examples:

> N. gonorrhea (have copies of the Opa-encoding genes, resulting in cells with different antigens and in cells that express different antigens over time.)

>Influenzavirus - flu

> Trypanosoma brucie gambiense – sleeping sickness

Penetration into the Host Cell

Figure 15.2

Penetration into the Host Cell Cytoskeleton

• Microbes attach by adhesions

• Triggers signals in host cell that activates factors that results in the entry of some bacteria

• Bacteria produce invasions, which rearrange actin

• Causes cytoskeleton disruption

• Allows bacteria to enter

How Bacterial Pathogens Damage Host Cells?

If pathogen overcomes host defenses then microorganism can damage host cells by:

1.Using host cell nutrients

2.Causing direct damage

3.Inducing hypersensitivity reactions

4.Producing toxins

Using the Host’s Nutrients

• Bacteria require iron

• Most iron in body tightly bound to iron-transport proteins

• Some bacteria produce siderophores (a protein) - take iron away from iron-transport proteins

Direct Damage

• Use host cell for nutrients and produce waste products

• As pathogens metabolize and multiply in cells, cells usually rupture

• Then move onto other cells

Production of ToxinsTerminology:

• Toxin - Poisonous substances that contribute to

pathogenicity

- transported by blood or lymph

- inhibit protein synthesis, destroy red blood cells, disrupt nervous system

• Toxigenicity - ability to produce a toxin

• Toxemia - presence of toxin the host's blood

• Toxoid - inactivated toxin used in a vaccine

• Antitoxin - antibodies against a specific toxin

Types of Toxins (based on their position relative to microbial cell)

• Endotoxins from inside the cell. Released upon cell lysis.

• Exotoxins are secreted out of the cell during cell life

Exotoxins

Figure 15.4a

Produced inside some bacteria as part of growth and metabolism and then secreted

Diffuse easily within blood and rapidly travel throughout body

Destroy parts of host cells or inhibit metabolic functions

Three Principal Types of Exotoxin:1. A-B toxins (type III toxin)

> designated A & B parts which are both polypeptides.

>A- part, active (enzyme) components

>B-part, binding component

2. Membrane-disrupting Toxins (type II Toxin)

>cause lysis of host cells by disrupting plasma membrane through forming protein channels in plasma membrane & disrupting phospholipid portion of plasma membrane

3. Superantigens (type I toxin)

> bacterial protein that provoke very strong immune response

The action of an exotoxin (A-B toxin) ~diptheria toxin~

Membrane-disrupting toxins -Hemolysins

Alpha Hemolytic Streptococci

- secrete hemolysins that cause the incomplete lysis or RBC’s

Beta Hemolytic Streptococci

- secrete hemolysins that cause the complete lysis of RBC’s

Membrane-disrupting toxins - Leukocidins

• Enzymes that attack certain types of WBC’s

• 1. Kills WBC’s which prevents phagocytosis

• 2. Releases & ruptures lysosomes

• lysosomes - contain powerful hydrolytic enzymes which then cause more tissue damage

Exotoxins (based on the host cell they attached):

neurotoxins – attack nerve cells

cardiotoxins – attack heart cells

hepatotoxins – attack liver cells

leukotoxins – attack leukocytes

enterotoxins – attack the lining of the gastrointestinal

tract

cytotoxins – attack wide variety of cells

Notable Exotoxins

• Diptheria Toxin (Corynebacterium diptheriae)

• Erythrogenic Toxin (Strpetoccocus pyogenes)

• Botulinum Toxin (Clostridium botulinum)

• Tetanus Toxin (Clostridium tetani)

• Vibrio enterotoxin (Vibrio cholerae)

• Staphylococcus enterotoxin (Styphylococcus aureus)

Exotoxins

Exotoxin Lysogenic conversion

• Corynebacterium diphtheriae A-B toxin type III. Inhibits protein synthesis. +

• Streptococcus pyogenes Membrane-disrupting. Type II Erythrogenic. +

• Clostridium botulinumA-B toxin. Neurotoxin - flaccid

paralysis

Botox+

• C. tetaniA-B toxin. Neurotoxin - prevents

CNS inhibition - spastic paralysis

• Vibrio choleraeA-B toxin. Enterotoxin.

Stimulates cAMP to cause severe diarrhea

+

• Staphylococcus aureus Superantigen. Type I. Enterotoxin.

Endotoxin

Figure 15.4b

part of outer membrane of G -bacteriaendotoxins released when G - bacteria die exert affect by stimulating macrophages to release cytokines at very high levelsThe lipid portion of the lipopolysaccharide, called lipid A, is the endotoxin. Endotoxins are lipopolysaccharides instead of proteins.stimulate macrophages to release excess amounts of cytokines resulting to chills, fever, weakness, aching, and in extreme cases shock and even death contribute to miscarriagesactivate blood-clotting proteins, causing the formation of many small blood clots that block capillaries. Tissues thus deprived of their blood supply die. This is called disseminated intravascular clotting (DIC).

• Septic shock - Shock caused by bacteria

• a severe drop in blood pressure.

• Following phagocytosis and lysis of the gram-negative bacteria, the phagocytic cell secretes a polypeptide called tumor necrosis factor (TNF) or cachectin. This substance binds to many body tissues and alters their metabolism. One effect is damage to capillaries that increases their permeability and causes them to leak fluid, thus lowering blood pressure and leading to shock. The lowered blood pressure is also harmful to kidneys, lungs, and the digestive tract.

• Hemophilus influenzae type b (G – bacteria) in cerebrospinal fluid cause the release of both IL-1 and TNF, which weaken the protective blood-brain barrier and allow bacteria to enter the CNS. Septic shock is very dangerous—up to 50% of cases may be fatal.

Organisms that produce endotoxins include:

•    1. Salmonella typhi (typhoid fever)

•    2. Proteus (frequent cause of urinary tract infections)

•    3. Neisseria meningitidis (meningococcal meningitis)

• If bacteria have grown and produced endotoxins in material that is later sterilized, the endotoxins retain their potency even though no living bacteria are still present. A test called the Limulus amoebocyte lysate (LAL) can be used to detect even traces of endotoxin.

Endotoxins & the pyrogenic response:

Figure 15.6

PLASMIDS, LYSOGENY, AND PATHOGENICITY

 • Plasmids - small circular pieces of DNA that are not

part of the main bacterial chromosome and contain genes not found on the main chromosome

- replicated and passed on to daughter cells during cell division.

- may contribute to bacterial pathogenicity, often by carrying genes for making

toxins.

- with the plasmid, the bacteria cause additional harm to the host.

• Lysogeny – a state in which bacteriophages incorporate their DNA into the bacterial chromosome ,thus, becoming a prophage.

• Lysogenic cells - cells containing the prophage.

• Lysogenic conversion - genes carried on the phage DNA may give lysogenic cells new characteristics.

Toxins produced due to genes of prophages:

•      Diphtheria toxin

•      Erythrogenic toxin

•      Staphylococcal enterotoxin

•      Pyrogenic toxin

•      Botulinum neurotoxin

•      Capsule of Streptococcus pneumoniae (not exactly a toxin but contributes to virulence)

•      Vibrio toxin

Mechanisms of Pathogenicity

Figure 15.9