Lecture 3

Microbial Pathogenesis

Indigenous Microflora

• All the microbes that exist on or within a person.
• A fetus has none.
• A baby is colonised after birth by mother, food and air.
• Consists of approximately 100 trillion cells (compared to 10 trillion host cells)
• Comprises of 500-1000 different species

Bacteria on our Skin

• About 1 trillion bacteria
• Most common: Staphylococcus spp., Streptococcus spp., Corynebacterium spp.
• Preferably colonise warm and sheltered places (e.g. armpits)
• Metabolise sweat to produce body odour.

Dental Streptococcus

• Biofilms of bacteria
• 300 to 500 cells thick on surface of teeth (dental plaque).
• Mostly Streptococcus songs and S. mutans

Firmicutes and Bacteroides in the Gut

• >500 species of bacteria - weighs about 3.3 pounds
• Break down carbs and produce essential nutrients like vitamin K and B12
• Crowd out harmful bacteria

Vaginal Flora

• Mostly beneficial bacteria e.g. Lactobacillus family.
• Secrete lactic acid to protect against hostile invaders
• Hostile e.g. pathogen yeast, Candida albicans (vaginal thrush)

Latent Viruses

• HPV cause persistent (latent) virus infections (virus lies dormant within the cell)
• >100 types can infect humans, causing a variety of warts.
• Other latent viruses include: herpes virus (cold sores), and chicken pox virus (shingles).

Fossil Viruses

• About 1/12 of our genome consists of stretches of DNA from viruses that infected our ancestors millions of years ago

Earliest known infectious diseases

• Include TB, syphilis, parasitic worm infections (egyptian mummies)
• Bubonic plaque, small pox (all found BC)
• Rabies, anthrax, measles, diptheria, typhoid fever.

Proof of Germ Theory

• Four criteria designed to establish a causal relationship between a causative microbe and a disease:
• The microorganism must always be found in similarly diseased animals, but not in healthy ones.
• The MO must be isolated from a diseased animal and grown in pure culture.
• The isolated MO must cause the original disease when inoculated in a susceptible host.
• The MO must be resulted from the experimentally infected animals.

Symbiotic relationships

• Symbiosis: organisms live together in close association
• Mutualism: beneficial to both symbionts
• Neutralism: neither symbionts is affected by the relationship
• Commensalism: beneficial to only one symbiont
• Parasitism: harmful to one symbiont (host) and beneficial to the other (parasite).
• Synergism': two or more MOs team up to cause disease. Synergistic or polymicrobial infection.
• Pathogen: MO that causes disease (<3% of all MOs)
• Opportunistic pathogen: has the potential to cause disease e.g. in immunocompromised individuals

Periods in the course of infectious disease

• Incubation period: time between infection and onset of symptoms
• Prodronal period: patients feels out of sorts, but experiences no symptoms
• Illness: experience of symptoms associated with disease
• Convalescent period: time during which the patient recovers.

Human Carriers

• A person infected with a particular pathogen without showing disease symptoms.
• Passive carrier: carries pathogen, but never had the disease symptoms
• Incubatory carrier: patient is in incubation period (asymptomatic)
• Convalescent carrier: patient recovering from disease, but still carrying pathogen
• Active carrier: patient has completely recovered from the disease, but still carries pathogen

Types of Infection

• Localised: pathogens are contained at site of infection
• Systemic: pathogen spreads throughout the body
• Acute: rapid onset and rapid recovery
• Chronic: slow onset and slow recovery
• Latent: pathogen not completely eradicated after recovery and can cause symptoms in future (Varicella zoster virus, herpes virus)
• Secondary: disease that follows primary infection (pneumonia after mild respiratory infection).

Microbial Diseases:

• Infectious disease
• A pathogen colonies a person's body
• The pathogen causes a disease
• Microbial Intoxication
• A pathogen produce a toxin in vitro
• A person ingest the toxin.
• The toxin causes a disease

Steps in Pathogenesis of Infectious Disease

• Entry: 'portal of entry'
• Attachment: binding to the host tissue (colonisation)
• Multiplication: at infection site (localised infection)
• Invasion or spread
• Evasion of host defences (immune evasion)
• Damage to host tissue: symptoms, disability, death

Virulence Factors

• Promote attachment to host cells (adhesins)
• Help bacterium to enter host cells (invasins)
• Damage to host cell or tissue (cytolysins)
• Help bacteria to spread from local infection (spreading factors)
• Over-stimulate immune response (immunopathogenic factors)
• Mediate immune evasion

Immune Evasion Factors

• Capsules (prevent opsonisation and phagocytosis)
• Destruction of phagocytes
• Inhibition of phagocyte chemotaxis
• Inhibition of phagocytosis
• Destruction of complement factors
• Destruction of immunoglobulins
• Intracellular replication