PMI02-2015

Question 1

Describe a classical infection.

Answer 1

Caused by a single organism, exogenous to normal flora

Organism colonises a susceptible host, multiplies and evades host defence

Damages host, usually by production of protein toxins (exotoxin)

Question 2

Give an example of a classical infection and its causative agent.

Answer 2

Anthrax - Bacillus anthracis

Whooping cough - Bordetella pertussis

Question 3

Describe a polymicrobial infection.

Answer 3

No single organism is associated with the disease state/infection associated with more than one microbe

May be a mixture of one type of organism (eg bacteria) or combinations of different microbes (eg bacteria and viruses)

Question 4

What issues are there with Koch’s postulates?

Answer 4

Organism should not be found in healthy hosts - what about pathobionts and commensals and helper strains?

Be able to isolate and grow the organism in pure culture - what about unculturable species?

Organism must cause disease when introduced into a healthy susceptible host - what about pathobionts/opportunistic pathogens which only affect immunocompromised hosts?

Question 5

Give an example of a primary and secondary infection of the lungs.

Answer 5

Primary viral infection = influenza or respiratory syncytial virus

Secondary bacterial infection = S. pneumoniae (and other pneumococci)

Question 6

How does a viral infection of the lungs predispose to a bacterial infection?

Answer 6

Initial viral infection causes damage to lung tissue and exposes basement membrane elements (eg fibrinogen) to which bacteria can adhere and infiltrate into host

Viral neuraminidase cleaves sialic acid residues on host cells to create more bacterial binding sites

Question 7

How does an impaired host immune response contribute to increased susceptibility to a secondary bacterial infection of the lungs?

Answer 7

Overproduction of inflammatory cytokines leads to infiltration of immune cells and alveolar architecture damage which allows bacterial infiltration

Question 8

What factors underpin septicaemia?

Answer 8

Virus as a primary infection

Bacteria as a secondary infection

Dysregulated host immune response

Question 9

Describe biofilms.

Answer 9

Matrix-enclosed population of microbes that can adhere to biotic and abiotic substances

Most prevalent manifestation of microbial communities

Composition changes over time, from person to person, between substrates and in response to environmental changes

Question 10

Give examples of biotic substrates that biofilms can grow on.

Answer 10

Skin

Mucosa

Teeth

Question 11

Give examples of abiotic substrates that biofilms can grow on.

Answer 11

Dentures, acrylics, resins

IV/urinary catheters

Abdominal drains

Stents

Ventilator tubes

Contact lenses

Question 12

What are the general steps in biofilm development in the oral cavity?

Answer 12

1. Primary colonisers with ionic then covalent interactions
2. Cell division and microcolonies
3. Secondary colonisers, coaggregation and coadhesion
4. Mature multi-species biofilm with selective pressures; succession until equilibrium is reached

Question 13

Give examples of some early colonisers in dental plaque formation.

Answer 13

Streptococcus species

Actinomyces naeslundii

Fusobacterium nucleatum

Porphyromonas gingivalis

Question 14

Give examples of some late colonisers in dental plaque formation.

Answer 14

Treponema denticola

Tannererlla forsythia

Question 15

What is the importance of the extrapolymeric substances of biofilms?

Answer 15

Mechanical stability

Facilitate cell-cell interactioin/communication

Reduce efficacy of antimicrobials/immune cells

Question 16

What are the advantages of living in a biofilm rather than planktonic growth?

Answer 16

Increased metabolic fitness due to nutritional co-operation

Increased genomic diversity and possible antibiotic resistance due to horizontal gene transfer

Increased stress resistance (eg aerobic bacteria lower oxygen tension for anaerobes)

Recalcitrance = reduced antibiotic penetrance and diffusion into biofilm

Question 17

What happens as an oral biofilm matures?

Answer 17

Complexity of community increases

Change from predominance of Gram positive facultative microbes to Gram negative anaerobes

Question 18

Give some examples of polymicrobial diseases.

Answer 18

Diabetic foot ulcers

Periodontits

Necrotising fasciitis

Denture stomatitis

Question 19

Describe how diabetic foot ulcers arise.

Answer 19

High blood sugar in diabetes causes:

• nerve damage/neuropathy
• reduced blood flow/microangiopathy
• chronic inflammation

Inappropriate foot care and foot injuries allow access of microbes

Question 20

What are the three major types of polymicrobial interactions within biofilms?

Answer 20

Physical (eg coaggregation)

Chemical (eg quorum sensing)

Nutritional (eg digestive consortium)

Question 21

Describe coaggregation.

Answer 21

Process why which genetically distinct, planktonic bacteria attach to each other via adhesins

Coaggregates influence development and composition of biofilms and microbes may influence the local environment

Question 22

Describe how Candida albicans and Staphylococcus aureus may associate.

Answer 22

C. albicans can produce hyphae

S. aureus can adhere to hyphae so when hyphae enter host tissue, the bacteria is carried in too (facilitates systemic bacterial infections)

Question 23

Describe what happens in denture stomatitis.

Answer 23

Biofilm accumulates on dentures and is colonised by fungi (typically Candida)

Constant contact of fungal/bacterial biofilm with oral mucosa causes inflammation

Question 24

What is quorum sensing?

Answer 24

Regulation of gene expression in response to fluctuations in cell population density

Question 25

How does quorum sensing work?

Answer 25

Microbes secrete quorum sensing molecules (QSMs)

When QSMs are in sufficient concentrations, they induce expression or repression of quorum-dependent target genes

Exceeding the critical threshold = changes in population behaviour

Question 26

Give examples of quorum sensing molecules and the type of bacteria they are produced by.

Answer 26

AutoInducer-2 (AI-2) = Gram negative and positive bacteria

N-acyl homoserine lactones (NAHLs) = Gram negative bacteria

Competence signalling peptides = Gram positive bacteria

Question 27

How can quorum sensing affect Candida albicans?

Answer 27

C. albicans has yeast and hyphae forms

Yeast typically associated with health, hyphae with disease

Transition can be controlled but is inhibited by QSM “farnesol”

C. albicans produces farnesol and prevents hyphae form

Question 28

What is a digestive consortium and why do they arise?

Answer 28

Multiple species cooperating with each other to completely degrade/metabolise complex substrates

Individual species are unable to metabolise all the substrates on their own - the more simple a substance becomes, the more useful it is to a wider variety of microbes

Question 29

Give an example of a digestive consortium.

Answer 29

Glycoprotein = Streptococcus species remove side chains

Peptides = Porphyromonas species cleave protein

Amino acids = Peptostreptococcus removes terminal amino acids

Short chain fatty acids, sulphates = Methanobrevibacter species produce methane

Desulfovibrio species reduce sulphate

Question 30

What are accessory pathogens?

Answer 30

Commensal microbes that can support or enhance the virulence of a different organism

Question 31

What is the minimum number of species usually required to form a dental abscess?

Answer 31

6-8

Question 32

How does P. gingivalis contribute to microbial subversion?

Answer 32

Produces gingipain which degrades C3

Manipulates neutrophils by blocking TLR and phagocytosis pathways

Inhibits macrophage responses by blocking TLR4 signalling and iNOS production

Question 33

How does Tannerella forsythia contribute to microbial subversion?

Answer 33

Produces karilysin which degrades C4

Question 34

What helps some “unculturable” species to survive in enviroments?

Answer 34

Helper strains