Infection and diseaseLecture 3

Bacterial toxinsPortals of exit

Common bacterial diseases

(7) Bacterial toxins• Toxins - Poisonous substances produced by microorganisms

– Toxigenicity - The ability to produce toxins.– Toxemia refers to the presence of toxins in the blood.

(a) exotoxins• Mostly produced by gram positive bacteria

• Soluble in body fluids

• Transported throughout blood / lymph

• Disease is often not due to the bacteria per se, but due to the exotoxins

• Most exotoxins are called AB toxins - 2 components: Active and Binding

Examples of exotoxins: Diptheria toxin

Diphtheria; nasopharyx is affected Toxin A inhibits protein synthesis in the host cell – leads to host cell death

Examples of exotoxins: Cholera toxin

• Vibrio cholera – diarrhoea

• Toxin A – increased cAMP – which controls the efflux of H2O ions from cells

• Increased secretion of water and ions into the intestine Diarrhoea

(b) Endotoxin

• Gram negative bacterial cellwall have lipid A (lipopolysaccharide -LPS) – endotoxin

• Important for pathogenesis

How are endotoxins released ?

• Complement-mediated lysis mediated of bacteria

• Phagocytic digestion of bacterial cells

• Antibiotics usage

What does an endotoxin do ?

ENDOTOXINInflammation

Secretion of Cytokines

Fever

BBB

Endotoxin are pyrogens

Killing of bacteria by some sterilization methods may to necessarily eliminate endotoxins

Endotoxins are heat stable

(8) Bacterial spores

• Formed by some bacteria under stress / nutrient depletion

• Most spore forming bacteria are Gram positive bacteria

• Can become a vegetative cell (what we normally refer to as bacteria) under favourable conditions

Bacterial spores

Unfavourable condition

Favourable condition

Bacterial spores

• Spores are highly resistant – to heat, cold, antibiotics

• Spores survive for centuries under harsh conditions

• Spores are dormant – no reproduction

• High levels of calcium dipicolinate – heat resistance / DNA protection

• High levels of sulphur

Portals of exit• Respiratory tract

– Coughing, sneezing

• Gastrointestinal tract– Feces, saliva

• Genitourinary tract– Urine, vaginal secretions

• Skin

• Blood– Biting arthropods, needles/syringes

Examples of bacterial diseases

Tetanus

• Exotoxin from Clostridium tetani

• Neurotoxin – causes muscle spasms

• Starts with pain in the jaw – inability to open jaw

• Spreads to all the muscles throughout the body

• 10% untreated – die due to the toxin

• Vaccine preventable (DPT /TT)

Disease causing organism

symptoms Reservoir Mode of transmission

Clostridium tetani Severe spasms, rigidity of muscles, lockjaw

Soil Puncture wounds contaminated by bacterial spores

Source: Royal College of Surgeons of Edinburgh, Scotland

Tetanus

Anthrax• Bacillus anthracis – spore forming

• Spores are present in soil

• Common disease of grazing animals

• Human infection: Pulmonary anthrax – inhalation of spores Gastrointestinal anthrax – eating of infected animal meat Cutaneous anthrax – hide porter’s disease (cuts in skin)

Disease is linked to exotoxin

Anthrax

Cutaneous anthrax

Anthrax – potential use in bioterrorism; Spores - inhalation

Plague• Yersinia pestis

• Major outbreak in the 14th

century – 200 million deaths

• Many minor outbreaks

• Transmitted through infected rat

fleas (rodents are reservoirs)

Plague: the disease

“Black death”

Plague: pathogenesis

• Resist digestion by macrophages

• Spread via lymphnodes /blood / shed from lungs

• Human-to-human transmission – cough /aerosol

• Acute inflammatory response

• Clogs capillaries

• Reduced blood supply – tissue death by necrosis

Cholera

• Vibrio cholera

• Transmitted by contaminated food /water

• Severe diarrhea (exotoxin)

• Dehydration / can be fatal in young children if untreated

Cholera

• Oral /IV rehydration / antibiotics

Typhoid fever

• Salmonella typhi

• Usually transmitted by contaminated food

• Can affect multiple organs – including brain, lungs, heart

• Small proportion (<5%) – asymptomatic carriers bacteria replicates Able to spread disease

Typhoid Mary

Asymptomatic carrier – cook; several families were infected, changed jobs. Quarantined for 3 decades

TB

• Mycobacterium tuberculosis

• Inhalation (long-term contact)

• ~90% - latent infection (No replication)

• ~10%- progression to pulmonary TB (immune system not able to control replication)

• Fever > 3 weeks, fatigue, cough, night sweat..

TB

• Extrapulmonary TB – brain, bone, joint

• Slow grower (~18 hours to double)

• Requires special antibiotics

• Requires long-term treatment

Food poisoning

Symptoms due to bacteria take > 2 days to manifest

Pre-formed exotoxins

Food poisoning

• Vomitting, abdominal pain

• Eg. Staphylococcus aureus

• Eg. Salmonella species

• Antibiotics may not prevent disease

Can normal flora cause disease ?

• Yes !

• Eg. E.coli (normally in the intestine) – can cause urinary tract infection