Mechanisms of Pathogenicity

How Microbes Enter a Host

Portals of Entry

mucous membranes

skin

the parenteral route

The preferred portal of entry

Salmonella typhi – mouth

Streptococci – respiratory tract

Numbers of invading microbes

Infectious dose - number of microbes required to cause infection in a host

ID₅₀ – infectious dose for 50% of a sample population

differs by organism and by portal of entry

cutaneous anthrax

inhalation anthrax

gastrointestinal anthrax

LD₅₀ – lethal dose of a toxin for 50% of a population

Adherence (attachment)

Adhesins or ligands on microbial surfaces bind to receptors on host cells

Locations of adhesins on bacterial cells:

glycocalyx

pili

fimbriae

flagella

Examples of adhesions:

Streptococcus mutans - glycocalyx

Actinomyces spp. – fimbriae

Escherichia coli and Shigella spp. – fimbriae

Treponema pallidum – end hook

Listeria monocytogenes – multiple adhesins for receptors

Neisseria gonorrhoeae - fimbriae

Staphylococcus aureus – cell wall proteins

Bioflms

may contain several different types of microbes

may resist disinfectants and antibiotics

How Bacterial Pathogens Penetrate Host Defenses

Capsules – impair phagocytosis

Organisms with capsules:

Streptococcus pneumoniae

Klebsiella pneumoniae

Hemophilus influenzae

Bacillus anthracis

Yersinia pestis

Components of the cell wall:

M protein – Streptococcus pyogenes

outer membrane protein (Opa) – Neisseria gonorrhoeae

waxes – Mycobacterium tuberculosis

Enzymes

coagulases – Stapholococcus aureus

kinases – dissolve clots

fibrinolysin (streptokinase) – Streptococcus pyogenes

staphylokinase – Staphylococcus aureus

hyaluronidase – hydrolyzes hyaluronic acid – Clostridium perfringens

collagenase – Clostridium spp.

IgA proteases – Neisseria gonorrhoeae and N. meningitidis

Antigenic variation – defense against antibodies

Examples:

Influenzavirus

Neisseria gonorrhoeae

Trypanosoma brucei gambiense

Penetration into cytoskeleton

invasins – rearrange host cell membrane – Salmonella spp

actin propulsion – Shigella spp. and Listeria spp.

. cadherin – movement from cell to cell

How Bacterial Pathogens Damage Host Cells

Using host cell’s nutrients:

siderophores bind iron

binding iron-transport proteins

Direct damage

rupturing

phagocytosis and extrusion

Escherichia coli

Salmonella spp.

Shigella spp.

Neisseria gonorrhoeae

enzyme excretion

motility

Toxin production

exotoxins

proteins

produced inside living cells and secreted

produced by both gram-positive and gram-negative bacteria

genes are on plasmids or phages

soluble in body fluids, easily transported throughout body

specific actions on specific tissues and organs

antitoxins are antibodies against specific toxins

toxoids are altered toxins that can stimulate antibody production

Three types:

A-B toxins (type III): A=active, B=binding

Membrane-disrupting toxins (type II)

protein channels

leukocidins

hemolysins

phospholipid disruption

superantigens (type III)

endotoxins

lipid A of lipopolysaccharide of gram-negative cell wall

only released when gram-negative bacterial cells die

stimulate macrophages to release cytokines

all endotoxins produce the same signs and symptoms:

fever

chills

weakness

generalized aches

shock

Plasmids, lysogeny, and pathogenicity

plasmids

resistance factors (R factors)

virulence factors

tetanospasmin

enterotoxins

dextransucrase

adhesins

coagulase

fimbriae

lysogenic conversion

diphtheria toxin

erythrogenic toxin

botulinum neurotoxin

cholera toxin

capsule of S. pneumoniae

Pathogenic Properties of Viruses

Viral mechanisms for evading host defenses

penetrate and grow inside host cells

attacking the immune system directly

Cytopathic effects of viruses – visible effects of viral infection

cytocidal effects

inclusion bodies

syncytium of multinucleate cells

changes in host cell function

interferon production

antigenic changes on cell surfaces

chromosomal changes

loss of contact inhibition/unregulated cell growth

Pathogenic Properties of Fungi, Protozoa, Helminths, and Algae

Fungi

trichothecenes

proteases

fungal capsules

drug resistance

toxins:

ergot

aflatoxin

mycotoxins of mushrooms:

phalloidin

aminitin

Protozoa

invasion and rupture of host cells

digestion of host cells

antigen variation to evade the immune system

Helminths

use of host tissues for growth

large parasitic mass

waste product accumulation

Algae

Dinoflagellates produce neurotoxins;

e.g. paralytic shellfish poisoning

Portals of Exit

Generally the same as the portal of entry

respiratory tract

gastrointestinal tract

genitourinary tract

skin

wounds