In terms of normal nasopharyngeal flora, what 5 bacteria are found in normal flora of the pharynx?
1) Streptococcus pyogenes (group A)
2) Haemophilus influenzae
3) Streptococcus pneumoniae
4) Neisseria meningitidis
5) Staph. aureus
What 2 bacteria make up vaginal flora pre puberty?
1) Skin flora
2) Lower GI flora - mainly e.coli
What 3 bacteria make up vaginal flora post puberty and why does it change?
Glycogen produced due to circulating oestrogens
1) Lactobacillus spp. lactobacillus acidophilus
Above ferments glycogen maintaining a ph of 3 and preventing overgrowth of other species
2) Skin flora
3) A few C.albicans
What is characteristic of the stomach and small intestine which inhibits bacterial growth, what 2 bacteria make up the flora here?
- Low gastric pH inhibits bacterial growth
- Predominantly aerobic bacteria
1) Acid-tolerant lactobacilli
2) H. Pylori
Counts increase daily, few or no anaerobes
What percentage of bacteria that make up the colon flora are anaerobes?
95-99%
Which 3 anaerobes make up 96-99% of the colon flora?
1) Bacteroides spp
2) Clostridium spp
3) Bifidobacteria spp
What 5 aerobic bacteria are found in the colon flora, they are all types of what bacteria?
1) Escherichia coli
2) Klebsiella spp
3) Enterobacter spp
4) Proteus spp
5) Citrobacter spp
All enteric gram-negative bacilli
How many organisms per gram and how many species have been found in the colon flora?
10^9 - 10^10 organisms/gram
At least 400 species identified
Give the 3 main benefits of normal flora?
1) Synthesis and excretion of vitamins - vitamins K and B12 secreted by enteric bacteria
2) Colonisation resistance - environmental manipulation (lowering pH) and producing antibacterial agents (colicins, bacteriocins, fatty acids, metabolic waste products)
3) Induction of cross reactive Ab - may have a protective effect
Give 6 conditions/diseases caused by normal flora?
1) Hypertension
2) Inflammatory bowel disease
3) Obesity
4) Metabolic disorders such as diabetes
5) Cancer
6) Infection - particularly C diff
What is the main risk factor for C Diff infection, why and how does the disease present?
1) Usually happens in people >60 yrs
2) Main risk factor is Abx treatment
3) Perturbation of normal colonic microflora allows C Diff overgrowth
4) Leads to toxin production
5) Diarrhoea, pseudomembranous colitis
What has faecal transplants been used to treat?
C. Diff
What 6 diseases has it been suggested that faecal transplants may be useful for?
1) MS
2) Chronic fatigue syndrome (ME)
3) Ideopathic thrombotic purpura
4) Ulcerative colitis
5) IBS
6) DM
What are the 3 pathological mechanisms linked to normal flora?
1) Overgrowth - excessive growth at normal sight
2) Translocation - presence at abnormal sight (spread from one surface to another or inoculation into a normally sterile sight)
3) Cross infection
Give an example of a disease caused by overgrowth of normal flora and why?
1) Vaginal thrush
2) Treated with broad spectrum Abx, inhibition of colonisation resistance
3) Develop vaginal itch with a creamy discharge
Give an example of a disease caused by translocation of normal flora from one surface to another?
Conjunctivitis
URTI - infects eye
Give an example of a disease caused by translocation of normal flora - through inoculation into a normally sterile sight?
1) Intravascular catheter infection
Skin flora inoculated into blood
Give an example of a disease caused by cross infection?
MRSA from nose infects lungs causing pneumonia - uncommon cause
Give 9 clinical conditions caused by normal flora?
1) Abscesses
2) Pneumonia
3) Gastroenteritis
4) Peritonitis
5) Dental caries
6) Peridontal disease
7) Pharyngitis
8) Endocarditis
9) Urogenital infections
What is pathogenicity and what are the 4 requirements for pathogenicity?
The capacity of a micro-organism to cause an infection
1) Transmissibility
2) Establishment in or a host
3) Harmful effects
4) Persistence (cant just be in contact with host for a short amount of time)
How is harm mediated in an infection?
Harm is often mediated by the host response rather than the pathogen itself - its the collateral damage to human tissue from destruction of the pathogen that causes the harm
What are the 6 components of the chain of infection?
1) Pathogenic organism (of sufficient virulence and in adequate numbers to cause disease)
2) Reservoir or source that allows the organism to survive and multiply
3) Mode of exit from the source
4) Mode of transmission from the source to the host
5) Portal of entry through which the pathogen can enter the host
6) Susceptible (ie. non-immune) host
What is virulence defined as?
Interchangeable with pathogenicity
Virulence is sometimes defined as the degree to which a micro-organism is able to cause disease
How does virulence and pathogenicity enable us to distinguish between s. aureus and streptococcus mutans?
Both are pathogenic
S aureus is more virulent that stretococcus mutans as it causes disease much more rapidly
What is meant by the LD50 and ID50 of a pathogen?
LD50 - Lethal dose - the dose of bacteria which would cause death in 50% of people infected
ID50 - infectious dose - the dose of bacteria which would cause infection in 50% of the people it came into contact with
What is colonisation and how is it facilitated?
Becoming maintained on or in the host
Facilitated by a receptor-ligand interaction (microbial ligand and host cell surface receptor)
What is infectivity?
The ability of a microorganism to become established in or on a host
Give the ligand receptor interaction of E coli?
P fimbriae : glycolipids on human uroepithelial cells
Give the ligand receptor interaction of S. pyogenes?
Protein-F : fibronectin (large multifunctional glycoprotein found in connective tissue, on cell surfaces and in various body fluids)
Give the ligand receptor interaction of Influenza?
Haemagglutinin : respiratory epithelial sialic acids receptors
What are virulence factors and what are they sometimes referred to as? 4
Components of microorganisms that result in harmful effects Encoded by virulence genes 1) Adhesins 2) Aggressins 3) Interferins 4) Modulins
Name the 6 virulence mechanisms?
1) Facilitation of adhesion
2) Toxic effects
3) Tissue damage
4) Interference with host defence mechanism
5) Facilitation of invasion
6) Modulation of the host cytokine responses
Endotoxin virulence factor is a component of what, found in what 2/3 bacteria?
Component of gram negative bacteria cell wall
Found in E coli and other gram-negative bacilli and neisseria meningitidis
How is endotoxin released, what is the active component and how does it damage host cells?
Released from dead/damaged cells
Active component is LPS
Binds to a number of host cell receptors
Induces a range of uncontrolled host responses
What component of LPS causes harm, what is the core of LPS made from?
Oligosaccharide core (not many sugars) Lipid A is the active component - a disaccharide-fatty acid complex
What is the host response to endotoxin?
SIRS (systemic inflammatory response syndrome)
What are the 3 components to SIRS, what does each include?
1) Uncontrolled T-lymphocyte response
- Cytokine release: TNFalpha, Gamma-interferon, interleukin 1
- Fever, rigors, hypotension, tachycardia, collapse
- Cardiac and or renal failure
2) Uncontrolled activation of clotting cascade
- Disseminated intravascular coagulation
- Depletion of clotting factors
- Bleeding tendency
3) Uncontrolled activation of complement
Give 2 diseases caused by an endotoxin?
1) Peritonitis caused by perforated appendix
E coli releases endotoxin
2) Neisseria meningitis - endotoxin mediated increase in vascular permeability causes loss of protein, fluid and plasma into the tissues, with pathological compensatory vasoconstriction
What are exotoxins?
Proteins produced by living bacteria, usually have quite specific effect/s on host
Botulism is caused by what bacteria and can infect people in what 3 ways?
Caused by clostridium botulinum (obligate anaerobe)
1) Ingestion of pre-formed toxin - contaminated food
2) Infection of dirty wounds - may be trivial wounds
3) Gastrointestinal colonisation - in infants
What is botulism and how does the botulinum toxin cause the effects of the disease?
Botulism - flaccid paralysis and respiratory failure (muscles are unable to contract)
Botulinum binds pre-synaptically and inhibits release of ACh at neuromuscular junction
What are the 5 Ds of clinical presentation of botulism?
1) Diplopia - double vision
2) Dysphagia
3) Dysarthria - difficulty speaking clearly
4) Dry mouth
5) Death - from respiratory failure
What bacteria causes tetanus, what is the method of infection?
Clostridium tetani (obligate anaerobe) Infection of dirty wounds - may be trivial wounds
What toxin is produced by clostridium tetani and how does it cause the symptoms of the disease?
Tetanospasmin
1) Produced on germination of spores
2) Binds to nerve synapses
3) Inhibits release of inhibitory neurotransmitters (eg. gamma-amino butyric acid) in the central nervous system
How does tetanus cause death?
Muscle rigidity - paralysed
Death through respiratory failurw
What is meant by opisthotonos?
spasm of the muscles causing backward arching of the head, neck, and spine, as in severe tetanus, some kinds of meningitis, and strychnine poisoning
Name 8 exotoxin mediated infections and the toxin they are caused by?
1) Cholera - vibrio cholerae
2) Diphtheria - Corynebacterium diphtheriae
3) C diff infection - diarrhoea/colitis
4) E coli O157 haemorrhagic colitis (verotoxin)
5) Staphylococcus scalded skin syndrome - S aureus
6) Whooping cough (pertussis) - Bordetella pertussis
7) Scarlet fever - streptococcus pyogenes
8) Scalded skin syndrome - s. aureus epidermolysin
What do the virulence factors of streptococcus pyogenes do and name 4 s.pyogenes sydromes?
Virulence factors promote connective tissue breakdown and invasion
1) Streptococcal sore throat
2) Erysipelas (an acute, sometimes recurrent disease characterised by large raised red patches on the skin)
3) Necrotizing fasciitis (inflammation of the fasciae of muscles or of other organs results in rapid destruction of overlying tissues)
4) Scarlet fever
Name 5 virulence factors of streptococcus pyogenes and what they do?
1) Hyaluronidase and streptokinase - break down connective tissue components, facilitating tissue invasion
2) C5a peptidase - inactivates complement compound C5a
3) Streptolysins -O and -H - lyse red and white blood cells and platelets
4) Erythrogenic toxin (phage encoded) - causes the rash of scarlet fever
5) Toxic shock syndrome toxin - streptococcal toxic shock syndrome is superficially similar to a syndrome of endotoxin release
What is meant by the fact that the erythrogenic toxin of streptococcus pyogenes is phage-encoded?
The gene encoding the toxin is only found in a bacteriophage (virus that infects bacteria) - the bacteria must have to be infected by that phage to produce the toxin
Name 2 bacteria which inhibit phagocytosis and how they do so?
1) S.pyogenes - M-protein binds fibrinogen and masks bacterial surface, blocking complement binding and opsonisation
2) S.pneumoniae - polysaccharide capsule inhibits opsonisation and therefore phagocytosis
Name 3 intracellular bacteria?
1) Mycobacterium tuberculosis
2) Salmonella typhi
3) Listeria monocytogenes
What 3 components make up viruses?
1) Genome - RNA or DNA
2) Capsid - protein
3) Envelope - lipid bilayer
What is one whole particle of a virus called?
Virion
What are the 6 components of a ‘generic’ virus life cycle?
1) Adsorption - receptor ligand interaction
2) Penetration - receptor mediated endocytosis
3) Uncoating - nucleic acid liberated from phagosome and replicated
4) Synthesis - nucleic acid and protein synthesis mediated by host cell enzymes
5) Assembly - Assembly of virus components is mediated by host and/or viral enzymes
6) Release - complete virus particles are released by budding of host cell membrane or disintegration of host cell
How many microbial cells does your body harbour?
10^14
In which regions are the 3 highest densities of microbial cells found?
1) Large bowel
2) Mouth
3) Axilla and groin
What is meant by normal flora?
Organisms found in a given location in a state of health
What is meant by colonisation?
Establishment at a sight in the body
What is meant by symbiosis?
two or more organisms co-exist in close physical association
In terms of symbiosis what is meant by mutualism, neutralism, commensalism, parasitism?
Mutualism - both organisms benefit from symbiosis
Neutralism - neither organism derives benefit or harm
Commensalism - one organism benefits, the other derives neither benefit nor harm
Parasitism - One organism (parasite) benefits at the expense of the other (host)
What is the difference between sterile and non sterile sights?
Non sterile sights have normal flora
Sterile sights have no normal flora
Why are non sterile sights, no sterile?
They are exposed to the environment either directly or indirectly
There is no mechanism in place to maintain sterility
