Mechanisms of Microbial Pathogenicity Slides

Robert Koch

* German physician

* experimented with Anthrax in cattle and

tuberculosis

* Major role in discovering that microorganisms

cause disease

* developed a protocol for determining if a microbe

causes a certain disease (late 1800s)

1) KOCH’S POSTULATES

The suspected pathogen must be found in every case of disease and not be found in healthy individuals

2)KOCH’S POSTULATES

The suspected pathogen can be isolated and grown in

pure culture

3)KOCH’S POSTULATES

A healthy test subject infected with the suspected pathogen must develop the same signs and symptoms of disease seen in postulate #1.

-unethical

4)KOCH’S POSTULATES

The pathogen must be re-isolated from the new host and

must be identical to the pathogen from postulate #2

PROBLEMS WITH KOCH’S POSTULATES

Koch's postulates are used to prove the cause

of an infectious disease, but not all microbes

cooperate.

exceptions/problems to Koch's postulates

• Some pathogens can cause several disease

conditions

• Some pathogens cause disease only in humans

• Some microbes have never been or cannot be cultured

Pathogenicity:

the ability to cause disease

Virulence

the degree or severity of disease

Pathogen must

Gain access to host via portal of entry (in high enough numbers)

Adhere to host tissues

Penetrate host tissues

-need to multiply before they are destroyed

Evade host defenses

-before immune system detects

Damage host tissues

-sometimes harms immune cells

Portals of entry

1) Mucous membranes (RT, GU, GI, conjunctiva) MOST COMMON

2) Skin (tough but requires cut/opening most of time)

3) Parenteral route (punture—> microb gets in)

Microbe is deposited directly into tissues when barriers are penetrated

NVADING MICROBES

A certain number of pathogens need to enter to cause disease (or death)

• That number varies for every pathogen and portal of entry.

ID50

infectious dose for 50% of a sample population

• Measures pathogenicity of a microbe

LD50

lethal dose for 50% of a sample population

• Often measures virulence of a microbe

Portal of Entry:Skin

10-50 endospores

Portal of Entry:Inhalation

10,000–20,000 endospores

Portal of Entry:Ingestion

250,000–1,000,000 endospores

ADHERENCE

-Almost all pathogens attach to host tissues

-Adhesins (ligands) on the pathogen bind to receptors on the host cells

Adhesins (ligands)

on the pathogen bind to receptors on the host cells

-Glycocalyx, fimbriae, protein, carbohydrate…

biofilms

(communities that

share nutrients)

-makes them sticky and hidden!

- helps with adherence

CAPSULES

Some bacteria have capsules external to the cell wall

Dual advantage!

1) Impairs phagocytosis evades host defenses

2) Sticky (adherence)

Capsules made in biofilms

Glycocalyx (capsules) produced by bacteria in a biofilm

allows the cells to adhere to host tissues and to medical

devices

CELL WALL COMPONENTS

Some resist phagocytosis (evasion)

• Waxy lipid (mycolic acid) resists phagocytosis (evasion)

• Some microbe proteins allow attachment to host cells (adherence)

ENZYMES

Many pathogens produce extracellular enzymes

• Break down host tissues

• Destroy host antibodies

Examples of Enzymes

1) urease

2) hyaluronidase

3) protease

4) collagenase

Enzymes- Urease

able to invade the lining of the stomach by producing virulence factors (including urease) that enable it pass through the mucin layer covering epithelial cells

-H. pylori enters the stomach lining right, (UREASE) neutralizes the ph closer to 7, and turns it into liquid, and now bact can swim through and get into lining of stomach to replicate

Enzymes- hyaluraonidase

Hyaluronan is a polymer found in the layers of epidermis that connect adjacent cells -keeps skin together

(b) Hyaluronidase produced by bacteria degrades this adhesive polymer in the extracellular matrix, allowing passage for microbes to go through

protease

has a capsule around bacterial cells.

Antibodies normally function by binding to antigens on surface of pathogenic bacteria.

—> Phagocytes bind to the antibody, initiating phagocytosis.

Some bacteria produce proteases, virulence factors that break down host antibodies to prevent phagocytosis

ENZYMES- collagenase

collagen in between epothelial cells- binds the cells together

produced by C. perfringens degrades the collagen between the endothelial cells, allowing the bacteria to enter the bloodstream.

PENETRATION/ENVASION-ANTIGENIC VARIATION

Pathogens alter their surface antigens (and antibodies are rendered ineffective) – Evasion

PENETRATION/ENVASION-Antigenic Drift

mutations in the genes for the surface proteins neuraminidase and/or hemagglutinin result in small antigenic changes over time.

PENETRATION/ENVASION-antigenic shift

simultaneous infection of a cell with two different influenza viruses results in mixing of the genes. The resultant virus possesses a mixture of the proteins of the original viruses. Influenza pandemics can often be traced to antigenic shifts

PENETRATION/ENVASION- invasions

surface proteins produced by bacteria that rearrange actin filaments of the cytoskeleton causes membrane ruffling

Penetration/Evasion- intercellular growth

enter host cells, replicate, and move around the cell by actin polymerization (penetration).

They can also move cell-to-cell in this way, and thereby avoid detection by the host immune system! (evasion)

HOST’S NUTRIENTS

-iron is required= pathogenic bacteria

-siderophores- proteins sereted by pathogens that bind iron more tightly than most cells

DIRECT DAMAGE

• Disrupting host cell function

• Using host cell nutrients

• Producing waste products

• Multiplying in host cells and cause ruptures

Toxins

poisonous substances produced by microorganisms

-prod few, cardiovascular problems, diarrhea, and shock

Toxienicity

ability of microorg to produce toxins

Toxemia

presence of toxin in the host’s blood

Intoxicatons

presence of toxin without microbial growth

EXOTOXINS

Proteins produced and secreted by bacteria

○ Soluble in bodily fluids; destroy host cells and inhibit

metabolic functions

● most often and potent released by Gram-positive

bacteria

EXOTOXINS- Antitoxins:

antibodies against specific exotoxins

EXOTOXINS- Toxoids

inactivated exotoxins used in vaccines

Lipid A

portion of lipopolysaccharides (LPS) of gram-

negative bacteria

• Released during bacterial multiplication and when gram-

negative bacteria die

Stimulate macrophages to release cytokines

• Causes fever and inflammation

Symptoms of Lipid A

Chills, fever, weakness, aches, shock or even death!

Symptoms just differ in severity

LPS Endotoxin

Lipopolysaccharide is composed of lipid A, a core

glycolipid, and an O-specific polysaccharide side chain.

Lipid A is the toxic component that promotes

inflammation and fever

Cytopathic effects (CPE)

are visible effects of viral infection on a cell

• Stopping cell synthesis

• Causing cell lysosomes to release enzymes

• Changing host cell function or inducing chromosomal

changes

• Inducing antigenic changes on the cell surface

• Loss of contact inhibition in the cell, leading to

cancer!!

PORTALS OF EXIT

•Respiratory tract

• Coughing and sneezing

•Gastrointestinal tract

• Feces and saliva

•Genitourinary tract

• Urine; secretions from the penis and vagina

•Skin

•Blood

Arthropods that bite; needles or syringes