Pathogens

what is the definition of pathogen

microorganisms capable of causing disease/damage to the host

identified by the set of virulence genes that are carried and expressed

what is the difference between infection and disease

the damage from a disease impairs host function

pathogenicity

ability of a parasite to inflict damage to the host

virulence

measure of the ability to cause damage to the host

depends on virulence factors

opportunistic pathogens

cause disease only in the absence of normal host resistance

the normal microbiome contains opportunistic pathogens

what are the two factors that determine virulence

invasiveness and toxigenicity

they ARE NOT mutually exclusive

what is invasiveness

ability of the microorganism to become established in the host, to overcome host defenses and to spread in the tissues

what is toxigenicity

the capacity of the microorganism to produce substances known as toxins that damage specific tissues of the host

what are the invasiveness virulence factors

adhesins, capsules, enzymes, invasins, T3SS and T4SS

what are adhesins

promote specific attachment to the host cell surface

can usually attach to a few cell types - they determine the site of colonization

what are the two types of adhesins

fimbriae/pill: polymers - loose attachment

afrimbrial: not filaments - close attachment

what is a capsule

in some bacterial pathogens, it prevents the pathogen from being destroyed by host immune cells (protection - blocks lysozyme)

mediates attachment (sticky)

capsule is not only a virulence factor

capsule is essential in these bacterial pathogens

streptococcus pneumoniae and haemophilus influenzae

what are the two forms of invasion of host tissues

penetration of epidermis (most common)

penetration of the mucosa (destruction of single cell layer)

how do pathogens use enzymes as virulence factors

attach themselves to the ECM

attach via fimbriae to collagen and hyaluronic acid

they can destroy the ECM to enter the cell

what is hyaluronidase

ECM enzyme that degrades hyaluronic acid (which holds host cells together)

staph, strep, clostridia

collagenase

ECM enzyme that degrades protein collagen in connective tissue

what is lecithinase

ECM enzyme that degrades lecithin in cell membrane

causes the lysis of RBC and detroys tissues

what is gas gengrene - clostridium perfringens

strict anaerobe

infection of deep wound

uses lecithinase to lyse host cells, collagenase and hyaluronidase to destroy ECM

what are hemolysins

some are enzymes, some are cytolysins (pore-forming)

cause lysis of RBC and a variety of other cells

what are invasins

surface proteins that allow microorganisms to enter cells (invade)

important in intracellular pathogens

invasion of host cells protect the bacterial pathogens against the host immune system and are a good source of nutrients

ex. mycobacterium, salmonella, listeria, chlamydia

what do pathogens need to do to grow inside host cells

modify the properties and behaviours of the host cell

block cell digestion, increase vacuole size, acquire nutrients, block host defense, etc.

how does type 3 secretion system work (T3SS)

forms a channel through the bacterial cytoplasmic membrane, periplasm, and outer membrane and then the host cell membrane so bacteria can inject protein into the host cell cytosol (diagram on slide)

it makes a “needle-like” structure between the bacteria and the host

what is the function of T3SS and T4SS

invasion of host cells

block phagosome maturation (digestion)

take control of the host cell

T4SS how work?

same as T3SS but does not have the needle-like structure

are T3SS and T4SS gram+ or gram- pathogens

gram-

does damage have to be caused by toxin production

no, it can be done by host’s immune system or from a large number of pathogens present

what are the two categories of disease of bacterial pathogens

infectious diseases: result from pathogen’s growth

intoxications: result from the presence of a specific toxin

what are the two categories of toxins

exotoxins and endotoxins

exotoxins

soluble, secreted/released when organism is lysed

usually proteins and heat-labile

highly immunogenic - inactivated by antibodies

very lethal

categorized by target (neurotoxins, nephrotoxins…)

AB toxins

2 subunit exotoxin that modify host cells

what are the subunits of AB toxins

enzymatic subunit (A) that modifies a target inside the host cell leading to damage

binding/cell entry subunit (B) that binds to specific cell receptors providing tissue/cell type specificity

Cholera toxin (AB toxin example)

5 B subunits attach to the intestinal cells (GM1 receptor) and send in the A subunit.

The A subunit produces cAMP which induces diarrhea (i think)

what are endotoxins

gram- bacterial pathogens (from lipid A of LPS)

released during multiplication or lysis of bacterial cells

heat stable and weakly antigenic (no antibodies)

very effective activator of immune system - cause fever, inflammation, septic shock

vaccines for exotoxins

can be made because they are antigenic and stimulate the host defense system to produce antibodies

because they are heat-labile, toxins can be inactivated into toxoids which still produce antibody responses and can be used in vaccines

vaccines for endotoxins

cannot be made because endotoxins cannot be inactivated by heat or formaldehyde and cannot be converted to a toxoid

what is a pathogenicity island

section of the chromosome encoding virulence factors