SBL100: Infectious disease

Biology: Lecture 2
 Microbes: Portals of entry

1) Skin:
Most microbes are not able to penetrate intact skin
Some fungi infect skin

2) Mucous membranes
Respiratory tract: eg. Influenza virus
Gastrointerstinal tract: eg. Cholera
Urogenital tract: HIV
Eye (conjunctiva): eg. adenovirus
 Microbes: Portals of entry
3) Parenteral (Blood-borne) route:
Microbe is deposited below the skin into the tissue
Eg. Blood transfusion, insect bite, tatooing (eg. HIV)

4) Vertical transmission:
Transmission from mother to child (eg. HIV)
What are bacteria ?
 Bacterial Structure

Chromosome: DNA material of the cell

Cell wall: Composed of peptidoglycan the cell wall maintains the
overall shape of a bacterial cell
Cell membrane: Lining the inside of the cell wall it provides a boundary for
the contents of the cell and a barrier to substances entering
and leaving.
Cytoplasm: Describes the inside of the cell and the contents
 Bacterial Shapes
There are 3 different shapes of bacteria

Balls or cocci
(Staphylococcus)

Rods
(Lactobacillus)
Spirals
(Campylobacter)

Bacteria with flagella are motile

 Gram stain

Diff. in
cell wall

1884: Hans Christian Gram; he developed this method to better visualize bacteria
All bacteria may be classified as Gram positive and Gram negative
 Classification of bacteria

• Shape

• Motility

• Gram stain

• Other property (eg.aerobic /ananerobic)

Mechanisms of bacterial
pathogenicity
 Microbial mechanism of pathogenicity

Number of
invading
microbes

Penetration or Damage
Portals of entry evasion of to host Portal of exit
host defenses cells

Adherence

Virulence factors
 (1) Adherence
• Adherence (attachment) is often an essential step in bacterial
pathogenesis or infection, required for colonizing a new host

– Adhesion - Process by which microorganisms attach themselves to

cells.

• Requires the participation of two factors: a receptor (a host

cell component) and an ligand (a mirobial component)
 (1) Adherence
• Adhesions/ligands bind
to receptors on host
cells
– Fimbriae/ pili
Escherichia coli
Neisseria gonorrhoeae
– M protein
Streptococcus pyogenes
(Group A Sterptococcus)
 Adherence examples

M protein: Group A Streptococcus (GAS) Pili /fimbriae: E.Coli / N. gonorrhoeae

 Why is adherence important ?

• Ability to colonize and cause

disease

• Ability to adhere
determines the host
specificity

• Potential drug target

(2)Formation of bacterial biofilms

Quorum sensing: ability to sense population density and alter gene expression
 Examples of biofilms
• Dental plaques
 Biofilms outside the body

Biofilm mats on stagnant water Biofilm mats on rocks – Yellowstone national park
 What triggers biofilm formation ?
• Bacterial attachment to surfaces

• Nutritional depletion

• Sub-inhibitory concentrations of antibiotics

• A critical population density of bacteria

 How do biofilms help bacteria ?

• Protection from immune response

• Protection from antibiotics

• Help tide over periods of low nutrition

• Microbial chatter (communication)

 Biofilms: Why do they matter ?

• Key mechanism in bacterial pathogenesis

• Important part of food chain

 (3) Bacterial capsule

• Some bacteria have a

polysaccharide layer outside
the cellwall called capsule

• Helps in attachment

• Helps evade host defences

Streptococcus pneumoniae
Haemophilus influenzae
Bacillus anthracis
 How does the capsule help bacteria
evade host defences ?
Capsulated bacteria

Prevent complement binding Allows survival inside Escape TLR recognition

and phagocytosis phagocytosis
Capsule inhibits phagocytosis
Capsule allows survival inside
phagocytes

Capsule may help resist digestion by lysosomal emzymes

Capsules allow escape of TLR recognition

(TLR)

No immune response
Capsules contribute to pathogenesis
 (4) Bacterial cell wall

• Outer layer

• Peptidoglycan (sugars
and aminoacids)

• The cell wall may carry

some surface proteins
Mycolic acid in cellwall helps resists
lysosomal digestion

Mycolic acid
in the cell wall

Mycolic acid in the cell wall resists digestion by lysosomal enzymes

Eg. Mycobacterium tuberculosis , Mycobacterium leprae

Proteins on the cell wall help evade
phagocytosis

 Phagocytosis X Phagocytosis
 Immune response X Immune response
X Disease  Disease
 (5) Bacterial enzymes
(a) Coagulase and kinase
(b) Hyaluronidase and collagenase
(c) IgA protease
 (a) Coagulase and kinase

 Inhibits phagocytosis
 Immune response – no access
 Antibiotics not effective

Eg. Staphylococcus aureus – skin infections

Strains that do not produce coagulase are not pathogenic

 (b) Hyaluronidase and collagenase
Digestion of
connective tissues
and Invasion of
tissues

Hyaluronidase: is present in Staphylococcus aureus (Skin infections)

and Streptococcus pyogenes (Sore throat)

Collagenase: is present in Clostridium perfringens (gas gangrene)

 (c) IgA protease
• An enzyme that can
degrade IgA antibodies

• Eg. Haemophilus influenza –

causes respiratory tract
infection / meningitis

• Help negotiate mucosal

defenses.
 (6) Membrane ruffling

Invasins : proteins expressed on the cell surface of various pathogens that alter actin
filaments of host cell cytoskeleton, allowing microbes to enter cells.
Infection and disease
Lecture 3
Bacterial toxins
Portals 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 cholerae – 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 cell wall

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 ?

Secretion of
Cytokines

Inflammation Fever
ENDOTOXIN

Blood brain
barrier
 Endotoxin are pyrogens

Killing of bacteria by some sterilization methods may not 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
Favourable condition

Unfavourable condition
 Bacterial spores

https://www.youtube.com/watch?v=NAcowlik
nPs

https://www.youtube.com/watch?v=NAcowliknPs
 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

• 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)

 Tetanus

Disease causing organism symptoms Reservoir Mode of

transmission

Clostridium tetani Severe spasms, rigidity of Soil Puncture wounds

muscles, lockjaw contaminated by
bacterial spores

Source: Royal College of Surgeons of Edinburgh, Scotland

 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
Plague: the disease

“Black death”
 Plague: pathogenesis
• Resist digestion by macrophages (Capsule)

• 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 cholerae

• 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

Pre-formed exotoxins

Symptoms due to bacteria

take > 2 days to manifest
 Food poisoning

• Vomiting, 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