HLSC 3P97 1st Midterm

What is microbiology?

The study of microorganisms and their interaction with other living organisms

Study of "invisible" organisms

What is medical microbiology?

The branch of clinical medicine devoted to the screening, diagnosis, prevention and treatment of diseases caused by infectious microorganisms

What are some groups of microbes?

Bacteria

Viruses

Fungi

Prions

Parasites

Protozoa

Helminths

Arthropods

When was the golden age of medicine?

1970s

Why was the 1970s the golden age of medicine?

Triad of: vaccines, antibiotics and improved hygiene

Factors that influenced the decrease in infectious disease incidence in the 20th century

Better housing

Better nutrition

Antibiotics

Improved hygiene and sanitation

Immunizations

Safer food and water

WHICH LEADS TO DECREASE IN HOST SUSCEPTIBILITY AND DISEASE TRANSMISSION

What is O?

Sugar on the bacterium that is part of LPS (component of cell membrane) O157 and O104

What is H?

Flagella (the tail)

When that H is H7 or H4

Protein

What does zoonotic mean?

Transmitted by another species

Epidemiology

Study of patterns of disease, where it occurs, when it occurs and in which populations

Anton von Leeuwenhoek (1632-1723)

First observation and description of microorganisms

Developed first microscope

Francesco Redi (1626-1697)

Proof against spontaneous generation

What is the spontaneous generation theory?

Organisms grew out of organic matter and transformed into something else

John Needham (1713-1781)

Placed mutton broth in flasks and then boiled it to sterilize it

Wanted to know if microorganisms come from broth or outside

Left it out on a bench and found broth cloudy because of spontaneous generation

Lazzaro Spallanzani (1729-1799)

Did same thing as Needham but stuck a cork in it

Result: clear broth, microorganisms negative

Therefore, micro-organisms came from air NO spontaneous generation

Louis Pasteur (1822-1895)

Put nutrient solution in flasks with long, curved necks (boiled and exposed to air)

Result: No growth of microorganisms therefore NO spontaneous generation

Germ Theory by Robert Koch

Identifying a microorganism as the cause of disease

Injected healthy mouse with anthrax from cows, the mouse became ill, then took it from the mouse and isolated it into a flask, he injected that isolated with healthy mice and they got sick too

Koch's Postulates

1. The microorganism must be present in every case of the

disease but absent from healthy potential hosts

2. The suspected microorganism must be isolated and grown in a pure culture

3. The same disease must result when the isolated microorganism is inoculated into a healthy host

4. The same microorganism must be isolated again from the

diseased host

5. TODAY: THE ORGANISM'S GENETIC MATERIAL MUST BE ISOLATED FROM INDIVIDUALS WITH DISEASE

The Spanish Flu (1918-1920)

3% of world population dead

Transmitted by service people from war

Causative Agent: B. influenzae (H.influenzae) which is made up into B.influenzae, streptococci and pneumococci

Found in healthy people as well

Physiological Adaptation

Change in gene expression in response to changes in the environment

Genetic adaptation

Overgrowth of a genetic mutant to become the predominant type in the population

Bacterial adaptation

If we are infected with bacterial meningitis, so we take antibiotics, just as a matter of chance some of the bacteria is muted where it is developing antibiotic resistant genes

Human vs. microbial adaptation

Us: The immune system

Them: Rapid reproduction, rampant, random mutation, limited nucleic acid repair capacity

How do we stay healthy?

Interaction between environment, host and agent

What does autochthonous mean?

In the same country

Outbreak

A small number of cases of the same infectious disease in very limited geographical space, sudden eg. Flu outbreak in LTC

Epidemic

An outbreak on a larger scale eg. if epidemic of Zika virus it has occurred in more than one geographic area, or flu is epidemic in Ontario because you expect it

Pandemic

Occurred all over the world eg. HIV/AIDS

Endemic

Occurs in a region naturally eg. Malaria occurs in Africa, TB to eastern Europe

What makes a microorganism a pathogen?

A microorganism that causes infection, usually resulting in disease

Synonymous with germ

Contagion

Can be passed along from one person to another eg. influenza

Exposure

State of close proximity to a potentially infectious organism: acute/chronic

Infection

Invasion and multiplication of microorganisms that are not normally present within the body

Disease

Medical condition associated with symptoms that adversely affect structure/function of tissues/organs/body parts

Chain of transmission

Infectious agent, reservoirs, portal of exit, means of transmission, portal of entry, susceptible host

Human pathogen transmission

Contact: Infection caused by contact and faeces

Body fluid exchange

Contamination: Infectious caused by contaminated water

Airborne: Droplet transmission, infection caused by airborne transmission

Controllable risk factors for contracting infectious disease

Hygiene

Stress

Diet

Exercise

Substance Use

Uncontrollable risk factors for contracting infectious disease

Heredity

Age

Environment (Pollutants, chemical exposure, water contaminants)

What is virulence?

Relative ability of a pathogen to cause damage to the host (infectivity of the microorganism that causes disease, disease severity)

Measurements (Case fatality, tissue invasiveness)

Determinants (Colonization, immune evasion and immunosuppression, intracellular access and nutrient hijacking)

How do we measure virulence?

Mortality

Microbial burden on tissue

Lifetime reproductive toll

Immunosuppression

Interpreting virulence

Relate the presence of a virulence factor/group of factors in the pathogen to a specific outcome in the host

Estimate of virulence for C. neoformans

Outcome: Time to death (a host variable)

Virulence factors (microbial variables which are capsule size, melanin production, growth rate)

Can you be a carrier but not be sick?

Yes, a contagious pathogen can go into a asymptomatic infected person which can be transmitted to a naive host

eg. Mary Mallon

Does one pathogen only cause one disease?

No it can cause many

eg. Varicella-zoster virus which is chicken pox and shingles

Organisms adapt in the host

eg. Many viruses and bacteria can cause food poisioning

What is taxonomy?

The science of naming organisms

What are the three domains?

Bacteria, Archaea, Eukarya

What are the three kingdoms?

Plants, Animals, Fungi

How do you make a name?

Genus name begins with capital letter, species name is the second name that starts with a lower case, both are in italics

What two groups are cells classified into?

Prokaryotic cells (Bacteria)

AND

Eukaryotic cells

(Plant and Animal)

What is a prion?

A protein, can cause disease if it is not normal folding

Symbiosis

Intimate association of 2 species of organism living together - no implication on outcome of association

Commensalism

1 benefits/other is unharmed

Mutualism

Both benefit

obligatory mutualism

sensu strictu = association is essential for both organisms, need each other in order to live

facultative mutualism

partners can successfully live apart but do better together

Parasitism

parasite benefits at expense of the host; association is essential for the parasite

The Human Microbiome Project (HMP)

Human Microbiome = Human Microbiota - Aggregate of microorganisms normally residing in human tissues

- Includes bacteria, fungi and archaea

Normal human has ~1013 body cells and 1014 resident

normal flora

Goals of the HMP

To characterize microbial communities in humans

To correlate changes with the state of human health

Benefits of microbiota

- Competition for niche with infectious organisms

- Production of inhibitors active against infectious organisms

- Intestinal production of Vitamin B / Vitamin K

- Immune stimulation

Opportunistic infection

pathogenicity of the microbiome when the balance between host and microbe is disrupted

Microbiome =

Microbiota = Normal flora = Microflora

Host

Organism that harbours the parasite and provides it with nourishment and habitat

Permissive (allows it to go through whole lifecycle) / Natural (organism chooses preference) / Accidental / Intermediate

Parasite

Infectious agent that is nourished and grows on or in a different organism while contributing nothing to the survival of its host

What is antibiotic resistance?

Survival of bacteria in the presence of an antibiotic/group of antibiotics to which it was previously susceptible

Genetically transmissible between bacteria (Conjugation, transduction, transformation)

Superbacterium/Superbug-bacterium that is resistant to more than one antibiotic (multi drug resistant organism)

Examples of antibiotic resistance

MRSA: multidrug resistant

Clostridium difficile: Multiple strains with different antibiotic resistance characteristics

Mycobacterium tuberculosis: Resistance to certain antibiotics

Mechanisms of multi-drug resistance

1. Antibiotic taken by patient gets into bacteria but bacterium degrades the antibiotic (some where along the way it picked up a gene that allows this to happen) so antibiotic won't work

2. Antibiotic enters bacterium, subject to antibiotic altering enzyme

3. Efflux pump, lets antibiotic come in but sends it into something that pumps it back out of the cell (P-gp Efflux Pump)

Etiology of Antibiotic Resistance

Antibiotic misuse (Lack of patient compliance (kill a bunch of bacteria, then if you stop the 10% that are left are going to be cleared by immune system but if infection comes back or you need that antibiotic again, then your antibiotic won't work) and Over-prescription / inappropriate prescription)

Extensive antibiotic use in livestock

Natural bacterial genetic mutation

Emerging pathogens

Incidence increasing after introduction into a previously uninfected host population

Re-emerging pathogens

Incidence increasing in an already- recognized host population

Clinical complications of measles

Ear infections, blindness, pneumonia, encephalitis, during pregnancy things

Sources of emerging and re-emerging pathogens

• Host population - e.g. Mycobacterium tuberculosis

• External environment - e.g. Legionella pneumophila

• Populations of other host species - e.g. HIV; variant Creutzfeldt-Jakob disease

Traditional factors influencing emergence

Microbial adaptation and change

Human demographics and behavior

Breakdown of public health Technology and industry International travel and commerce

Economic development and

land use

Novel factors influencing emergence

Human susceptibility to infection

Climate and weather

Changing ecosystems

Poverty and social inequality

War and famine

Lack of political will

Intent to harm

Prevalence

Total number of cases

R0

# of cases generated by a single case

Outbreak size (OS) reflects?

# primary cases (PCs)

PC size

R0

Size of popn at risk

What is the purpose of vaccination?

To achieve a threshold at which R0=1

Herd immunity

Proportion of the population that must be vaccinated to achieve R0=1

Who are the susceptible members of the population that is protected by herd immunity?

Young children and elderly

No vaccination and no herd immunity leads to?

Huge outbreaks

Some vaccination equally distributed and full herd immunity leads to?

No outbreaks

Modes of infectious disease transmission

Passing a communicable disease from one member of a species to another

Direct contact (droplet and physical contact)

Indirect contact (contaminated surface)

Airborne

Fecal-oral

Vector-borne (insect bite)

Vertical transmission

Mother to child

Horizontal transmission

Person to person

Natural History of Disease General Model

Clinical disease

Subclinical disease

Biochemical/physiological markers

Lifestyle/environmental factors

OR

Diagnosis

Treatment

Secondary prevention

Outcome (healthy, cured, controlled, dead)

Prevention Strategies

Promoting health and primary preventions, biological onset of disease, preclinical phase (secondary prevention), symptom appear, clinical phase (Dx and therapy), tertiary prevention

How does bacteria achieve genetic adaptation and diversity?

Spontaneous mutation

Lateral gene transfer

Gene jumping utilizing transposable genetic elements

What is lateral gene transfer?

Genetic material gets transmitted in a line from one gene to another (transformation, transduction, conjugation)

Bacterial transformation

Chromosome undergoes mutation, bacteria dies and releases DNA, a stretch of that DNA has mutation and gets absorbed into a healthy recipient cell

Bacterial transduction

Two fighting, one is a virus (bacterial phage), bacterial phage enters bacterium and breaks apart its DNA, it is then released from bacterium and lands on another bacterium and inserts that bit of DNA from bacterium 1 to bacterium 2 (lateral gene transmission 2)

Bacterial conjugation

Two bacteria, one has a pilus, this pilus where plasmid DNA can be into recipient bacteria, the one that receives it is female

Transposon

Transposable element

Jumping gene

Mutagens

Brings two genes close together that were not initially close

Two arms of immunity

Innate immunity and adaptive immunity

Basis of immunity

Antigen=non-self

Self cells that respond

Cytokines made by responding cells

Primary lymphoid organs

Bone marrow and thymus

Thoroughfares required for cell traffic

Capillaries/blood vessels

Lymphatic vessels

Secondary lymphoid organs

Spleen and lymph nodes

First line of defence

Barriers: skin (specialized cells in our skin trap antigens and move it to a lymph node), membranes, mucous and cilia

Secondary line of defence

Innate immunity (rapid response)

Third line of defence

Adaptive immunity (slow response)