Microbiology Chapter 15: Mechanisms of Pathogenicity

Pathogenicity

microbe's ability to cause disease by overcoming host cell defenses

Virulence

the degree of pathogenicity (how severe it is)

Portals of entry for microorganisms

mucous membranes and skin

Respiratory tract portal of entry

Easiest and most frequent route

Through breathing in droplets, spores, etc

Ex. cold, flu, tuberculosis

Gastrointestinal tract portal of entry

Via water / food

ex. polio, giardiasis, cholera

Genitourinary tract portal of entry

Via sexual contact

ex. HIV, herpes, gonorrhea

Conjunctiva

mucous membrane portal of entry of the eye

Mucous membranes

Moist, soft tissue lining of body cavities/organs/tracts open to external environment

Mucous membrane examples for portals of entry

Respiratory tract

Gastrointestinal tract

Genitourinary tract

Conjuctiva

Skin as portal of entry

Unbroken skin impenetrable by most microbes

Openings more vulnerable to infection

ex. hair follicles, sweat gland ducts

Parenteral route

breach of skin that results in the deposition of microbes into tissue beneath the skin or mucous membrane

directly enters blood, body fluid, deep tissue

ex. puncture wounds (stepping on nail)

Invading microbe numbers

Few can be overcome by host defenses

Disease likelihood increases with pathogen number

ID₅₀

Infectious dose 50

number of microbes required to produce a demonstrable infection in 50% of test population

used to express the virulence of a microbe

LD₅₀

Lethal dose 50

dose required to kill 50% of test population

used to demonstrate the potency of toxic

High vs low ID₅₀ and LD₅₀

Lower the number higher the

ID - virulence

LD - potency

Pathogenic adherence

process by which pathogens attach to host tissue utilizing adhesins or ligands

What are adhesins/ligands?

surface molecules on pathogen that bind specifically to complementary surface receptors on host cells

majority are glyco- or lipo- proteins

located on glycocalyx or other microbial cell surface

Definition of biofilms

mass of cells (community) clinging to surfaces

allows for nutrient sharing and protection

can be several layers thick with different cell types

Benefit of biofilms

Resistance to

disinfectants + antibiotics

phagocytosis

What is the function of bacterial capsules?

a structure that inhibits phagocytosis

produced by Streptococcus pneumonia + Bacillus antracis

M protein

a cell wall component of some cells’ surface that resists acids/temperature

mediates attachment to epithelial cells and avoids phagocytosis

ex. in Streptococcus pyogenes

Coagulase

Exoenzyme that converts fibrinogen into fibrin

fibrin forms a cage-like barrier layer that protects bacteria from phagocytosis

produced by some Staphylococci

Kinase

enzyme class that dissolve fibrin blood clots

allowing for the spread of infection (blood clots cannot block spread)

produced by Staphylococcus aureus + Streptococcus pyrogenes

Hyaluronidase

enzyme that hydrolyzes hyaluronic acid

(the polysaccharide that holds connective tissue cells together)

modifies (increases) permeability of connective tissue

causes leaks promoting spread of infection

Collagenase

enzyme that breaks down the protein collagen found in connective tissue

IgA protease

enzyme that destroys antibodies in IgA class

How does antigenic variation benefit pathogens?

pathogens are able to alter their surface antigens

makes antibodies unable to recognize them

immune system must "re-learn" the pathogen

Antigenic variation organism

Trypanosoma brucei

has multiple surface antigens it can express 1 at a time

Surface antigens

foreign proteins on pathogens

elicit response by immune system for antibodies to target

Invasins

surface proteins that rearrange the actin filaments of the host cytoskeleton

triggers host cell to take in the pathogen which can then reproduce inside cell

through "membrane ruffling" (disruption in cytoskeleton)

Toxemia

presence of toxins in the blood

Toxins

cause most damage done by bacteria

poisonous substances produced by certain microorganisms

usually proteins

responsible for symptoms of disease

Exotoxins

mostly made by Gram+ cells

highly specific proteins produced inside the organism

excreted into surroundings or released upon lysis

can destroy cell structure, inhibit metabolic functions of host cell

Types of exotoxins

A-B toxins (most common)

Membrane-disrupting toxins

Superantigens

Structure of A-B toxin

consists of two polypeptide parts: subunits A and B

A - active (enzyme) component

B- binds to host cell receptor

How do A-B toxins work

A-B released from bacterium

B binds to host cell receptor

Exo toxin enters by endocytosis

Once in cell, subunits A + B separate

A alters function of host cell (ex by inhibiting translation)

B released from host cell

Botulinum toxin

A-B neurotoxin by Clostridium botulinum

acts at neuromuscular junction

works to prevent proper muscular contraction

leads to paralysis

one of most potent toxins

Tetanospasmin

A-B neurotoxin by Clostridium tetani

prevents muscle relaxation

results in uncontrollable muscle contraction

Cholera toxin

A-B enterotoxin (works in gut)

causes cells to secrete large amounts of fluids and electrolytes

resulting in severe (clearish white) diarrhea

How does cholera toxin work

B subunit binds to epithelial cells (that line intestines)

A subunit hyper stimulates particular enzyme cell makes

causes cells to secrete large amounts of fluids + electrolytes

normal muscle contraction inhibited

Membrane disrupting toxins

Disrupt host cell plasma membrane (first layer of defense)

Results in lysis

Mechanisms of action of membrane disrupting toxins

Pore formation (opening forms in membrane)

Phospholipases (enzyme breaking down phospholipids of membrane)

Superantigens

antigens that bind nonspecifically to T cell receptors

hyper stimulates immune response

causes mass activation of T cells, triggering massive cytokine release

Cytokines and symptoms of too much

small proteins that regulate immune response

mass release causes fever, nausea, shock (depression of blood pressure)

Why is a large amount of cytokines toxic?

triggers a heightened inflammatory response

damages tissues and leaves host at risk of secondary infection

Endotoxins

lipids that act as toxins within a cell

part of the outer portion of the cell wall of Gram-negative bacteria

the lipid portion of LPS is the endotoxin

released when bacterial cell dies and lyses

How do endotoxins work in the host cell?

G- cell engulfed by macrophage, release LPS when lyses

endotoxin stimulates macrophage to release cytokines

cytokines enter bloodstream, travel to hypothalamus and induce it to produce prostaglandins

which resets body's “thermostat” raising temp and inducing fever

Septic shock

characterized by low blood pressure

reduces amount of blood circulation to vital organs

How can septic shock be caused?

can be caused by LPS fragments (endotoxins) triggering a massive inflammatory response

Why is it so important to know what kind of bacteria is causing an infection

Some drugs work by lysing cells, so for endotoxin producing pathogens will compound issue