Ch 15- Microbial Mechanisms of Pathogenicity

pathogenicity

ability to cause disease

virulence

the degree (intensity) of pathogenicity

portals of entry

mucous membranes

skin

direct deposition beneath skin/membranes (parenteral route)

most have preferred portal of entry

mucous membranes

respiratory tract- Easiest, most freq (inhale dust/moisture)

GI tract- contaminated fingers

Genitourinary tract- STI or cut/abrasion

conjunctiva

skin

Unbroken skin impenetrable by most microorganisms

Some microbes go thru openings in skin (hair follicles and sweat gland ducts)

Larvae of hookworm bore through intact skin

some fungi grow on keratin or infect skin itself

parenteral

deposited directly into tissues beneath skin/mucous membranes when barriers are penetrated/injured

injections, bites, cuts, wounds, surgery, and splitting

ID50

infectious dose for 50% of a sample population

Measures virulence of MICROBE

LD50

lethal dose for 50% of a sample population

Measures potency of a TOXIN

id50 bacillus anthracis

Skin 10–50 endospores

Inhalation 10,000–20,000

Ingestion 250,000–1,000,000

ld50 toxins

Botulinum 0.03 ng/kg

Shiga toxin 250 ng/kg

Staphylococcal enterotoxin 1350 ng/kg

adherence

Almost all pathogens attach to host tissues

Adhesins (ligands) on the pathogen bind to receptors

on the host cells

glycocalyx ex

Streptococcus have this

mutans (made of dextran) enables bacteria to

adhere to teeth

fimbriae ex

fimbriae of Actinomyces

adheres to the glycocalyx of S. mutans

viral spikes ex

spikes of SARS-CoV2 –

adhere to ACE2 receptor on host cells

capsules adherence

Glycocalyx around the cell wall

impair phagocytosis

Streptococcus pneumonia

pneumonia

Haemophilus influenzae

pneumonia and meningitis

Bacillus anthracis

anthrax

Yersinia pestis

plague

cell wall components

m protein

opa

waxy lipid

m protein

resists phagocytosis

• Streptococcus pyogenes

opa

protein allows attachment to host cells

• Neisseria gonorrhoeae

waxy lipid

(mycolic acid) resists digestion

• Mycobacterium tuberculosis

enzymes

coagulases

kinases

hyalouronidase

collagenase

iga proteases

coagulases

coagulate fibrinogen

Kinases

digest fibrin clots

Hyaluronidase

digests polysaccharides that hold

cells together

Collagenase

breaks down collagen

IgA proteases

destroy IgA antibodies

antigenic variation

Pathogens alter their surface antigens; the antibodies that a host made

against those antigens are rendered ineffective

• Ex:

influenza virus

Neisseria gonorrhoeae

Trypanosome brucei gambiense

penetration into host

invasin

actin

phagocytes

invasin

Surface proteins produced by bacteria that rearrange

actin filaments of the cytoskeleton

• Cause membrane ruffling

actin

used to move from one cell to next

Shigella and Listeria

survival inside phagocytes

Requirement for low pH in phagolysosome

• Escape from phagosome before lysosomal fusion

• Prevention of fusion of lysosome with phagosome

biofilms

Resist antibiotics and disinfectants

• Involved in 65% of all infections

• Play a role in evading phagocytes

– Biofilm bacteria more resistant to phagocytosis, shielded by extracellular

polymeric substance (EPS) of biofilms

siderophores

uses host’s nutrients

Iron is required for most pathogenic bacteria

• proteins secreted by pathogens

that bind iron more tightly than host cells

direct damage

Disrupts host cell function

• Uses host cell nutrients

• Produces waste products

• Multiplies in host cells and causes ruptures

toxins

poisonous substances produced by

microorganisms

• Produce fever, cardiovascular problems, diarrhea,

and shock

toxigenicity

ability of a microorganism to produce a

toxin

toxemia

presence of toxin in the host’s blood

intoxication

presence of toxin without microbial

growth

exotoxins

Proteins produced and secreted by bacteria

– Soluble in bodily fluids; destroy host cells and inhibit metabolic functions

– HIGHLY specific for targets

– Some highly lethal

antitoxins

antibodies against specific exotoxins that provide immunity

toxoids

inactivated exotoxins used in vaccines

ab toxins

enzyme component (A part)

binding component (B part)

• Diphtheria toxin

ab toxin action

bacterium produces and releases ab toxin

b attaches to host cell receptor

plasma membrane of host cell folds inward where A-B exotoxin touches plasma receptor

exotoxin enters cell by receptor-mediated endocytosis

pinocytosis- plasma membrane closes and ab are bubbled in

ab separate

a- alters host cell function

b- released from host cell

DIPTHERIA TOXIN

a toxin

part of ab exotoxin

alters host cell funct by inhibiting protein synth at end

enzyme component

b toxin

binding component

gets released at end

part of ab exotoxin

genotoxins

damage DNA (causing mutations,

disrupting cell division, and leading to cancer)

membrane disrupting toxins

lyse host cells by

disrupting plasma membranes

leukocidins

kill phagocytic leukocytes (wbc)

hemolysins

kill erythrocytes by forming protein channels

streptolysins

hemolysins produced by streptococci

superantigens

bacterial proteins that combine w macrophage protein

cause an intense immune response

due to release of cytokines from host cells (T cells)

• Cause symptoms of fever, nausea, vomiting,

diarrhea, shock, and death

exotoxin types

anitoxin

toxoid

ab toxin

genotoxins

membrane disrupting toxins

leukocidins

hemolysins

streptolysins

superantigens

botulism

Clostridium botulinum

A-B Neurotoxin

prevents transmission of nerve impulses; flaccid paralysis

tetanus

C. tetani A-B Neurotoxin

blocks nerve impulses to muscle relaxation pathway; uncontrollable muscle contractions

diptheria

Corynebacterium diphtheriae

A-B Cytotoxin

inhibits protein synthesis, especially in nerve, heart, and kidney

cells

scalded skin syndrome

S. aureus

A-B Exotoxin

causes skin layers to separate and slough off.

cholera

V. cholerae

A-B Enterotoxin

causes secretion of large amounts of fluids and electrolytes that

result in diarrhea

travelers diarrhea

Enterotoxigenic E. Coli and Shigella spp.

A-B Enterotoxin

causes secretion of large amounts of fluids and electrolytes that

result in diarrhea

anthrax

bacillus anthracis

A-B

TWO A components enter the cell via the

same B component. A proteins cause shock and reduce immune

response

gastric (stomach) cancer

Helicobacter spp

A-B toxin

Genotoxin; causes breaks in DNA

colorectal cancer

E. coli

A-B toxin

Genotoxin (colibactin); binds to adenines

in DNA.

skin and soft tissue infection

Methicillin-resistant S. aureus

Membrane-disrupting

The Panton-Valentine leukocidin found in community-acquired strain of MRSA

makes pores in WBC membranes

gas gangrene and food poisoning

C. perfringens and other species of

Clostridium

Membrane-disrupting One cytotoxin (exotoxin) causes massive red blood cell destruction (hemolysis); enterotoxin (exotoxin) related to food poisoning

and causes diarrhea.

antibiotic diarrhea

Clostridioides difficile Membrane-disrupting Enterotoxin

causes secretion of fluids and electrolytes that results in diarrhea;

acts as cytotoxin that disrupts host

cytoskeleton.

food poisoning

S. aureus

Superantigen

Enterotoxin causes secretion of fluids

and electrolytes that results in diarrhea.

toxic shock syndrom

S. aureus

Superantigen

Causes secretion of fluids and electrolytes from capillaries that

decreases blood volume and lowers blood pressure.

lipid A

ENDOTOXIN

(exotoxins r proteins)

portion of lipopolysaccharides (LPS) of gn bacteria

• Released during bacterial multiplication and when gram-

negative bacteria die

– Stimulate macrophages to release large quantities of

cytokines

– fever, chills, weakness, generalized aches

– disseminated intravascular coagulation

– endotoxic shock: life threatening drop in blood

volume and blood pressure

– May weaken blood-brain barrier

endotoxin pyrogenic response

• A macrophage ingests a gram-negative bacterium

• bacterium is degraded in vacuole, releasing endotoxins that induce

macrophage to produce cytokines, interleukin-1 (IL-1), and tumor necrosis factor alpha (TNF-α).

• cytokines released into blood- stream by macrophages, travel to hypothalamus (temp center)

• cytokines induce hypothalamus to produce prostaglandins, which reset

body's "thermostat" to higher temperature, producing fever

Limulus amebocyte lysate (LAL) assay

test for endotoxins

• Blood of horseshoe crabs contains amebocytes

• Amebocytes lyse in the presence of endotoxin,

producing a clot

endotoxin source

gn ONLY

exotoxin source

gp, gn

plasmids

may carry genes for toxins, production of antibiotics,

and enzymes

r plasmids

carry genes encoding resistance to some

antibiotics

Virulence plasmids

carry genes that affect a

microorganisms pathogenicity

Tetanus neurotoxin

▪ Staphylococcal enterotoxin

▪ Adhesins and coagulase of Staphylococcus aureus

lysogenic conversion

changes characteristics of a microbe

due to incorporation of a prophage

– Genes for diphtheria toxin, erythrogenic toxin

cytopathic effects (CPE)

visible effects of viral infection on a cell

• Stopping cell synthesis

• cell lysosomes release enzymes

• inclusion bodies in the cell cytoplasm

• Fusing cells to create syncytium

• Changing host cell function/ inducing chromosomal

changes

• Inducing antigenic changes on the cell surface

• Loss of contact inhibition in the cell, leading to

cancer

• Inducing a cytokine storm (SARS-CoV-2 and

Alphainfluenzavirus)

fungi definition and ex

Toxic metabolic products

• Provoke an allergic response

• Trichothecene

• Proteases

– Candida albicans

– Cryptococcus neoformans

• Ergot

• Aflatoxin

• Mycotoxins

• Phalloidin and amanitin

Trichothecene toxins

inhibit protein synthesis

proteases

modify host cell membranes

– Candida albicans

capsules

prevent phagocytosis

– Cryptococcus neoformans

ergot

alkaloid toxins that cause hallucinations

aflatoxin

carcinogenic toxin produced by

Aspergillus

mycotoxin

produced by mushrooms and are

neurotoxic

• Phalloidin and amanitin

Protozoa

Presence of these and their waste products causes symptoms

• Avoid host defenses by:

– Digesting cells and tissue fluids

– Growing in phagocytes

– Antigenic variation

Giardia intestinalis

Digesting cells and tissue fluids

Toxoplasma gondii

growing in phagocytes

trypanosoma

–Antigenic variation

portals of exit

Respiratory tract- coughing sneezing

GI tract- feces saliva

• Genitourinary tract

• Urine; secretions from the penis and vagina

• Skin

• Blood

• Arthropods that bite; needles or syringes