PMI02-2015 Flashcards
Describe a classical infection.
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)
Give an example of a classical infection and its causative agent.
Anthrax - Bacillus anthracis
Whooping cough - Bordetella pertussis
Describe a polymicrobial infection.
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)
What issues are there with Koch’s postulates?
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?
Give an example of a primary and secondary infection of the lungs.
Primary viral infection = influenza or respiratory syncytial virus
Secondary bacterial infection = S. pneumoniae (and other pneumococci)
How does a viral infection of the lungs predispose to a bacterial infection?
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
How does an impaired host immune response contribute to increased susceptibility to a secondary bacterial infection of the lungs?
Overproduction of inflammatory cytokines leads to infiltration of immune cells and alveolar architecture damage which allows bacterial infiltration
What factors underpin septicaemia?
Virus as a primary infection
Bacteria as a secondary infection
Dysregulated host immune response
Describe biofilms.
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
Give examples of biotic substrates that biofilms can grow on.
Skin
Mucosa
Teeth
Give examples of abiotic substrates that biofilms can grow on.
Dentures, acrylics, resins
IV/urinary catheters
Abdominal drains
Stents
Ventilator tubes
Contact lenses
What are the general steps in biofilm development in the oral cavity?
- Primary colonisers with ionic then covalent interactions
- Cell division and microcolonies
- Secondary colonisers, coaggregation and coadhesion
- Mature multi-species biofilm with selective pressures; succession until equilibrium is reached
Give examples of some early colonisers in dental plaque formation.
Streptococcus species
Actinomyces naeslundii
Fusobacterium nucleatum
Porphyromonas gingivalis
Give examples of some late colonisers in dental plaque formation.
Treponema denticola
Tannererlla forsythia
What is the importance of the extrapolymeric substances of biofilms?
Mechanical stability
Facilitate cell-cell interactioin/communication
Reduce efficacy of antimicrobials/immune cells
What are the advantages of living in a biofilm rather than planktonic growth?
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
What happens as an oral biofilm matures?
Complexity of community increases
Change from predominance of Gram positive facultative microbes to Gram negative anaerobes
Give some examples of polymicrobial diseases.
Diabetic foot ulcers
Periodontits
Necrotising fasciitis
Denture stomatitis
Describe how diabetic foot ulcers arise.
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
What are the three major types of polymicrobial interactions within biofilms?
Physical (eg coaggregation)
Chemical (eg quorum sensing)
Nutritional (eg digestive consortium)
Describe coaggregation.
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
Describe how Candida albicans and Staphylococcus aureus may associate.
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)
Describe what happens in denture stomatitis.
Biofilm accumulates on dentures and is colonised by fungi (typically Candida)
Constant contact of fungal/bacterial biofilm with oral mucosa causes inflammation
What is quorum sensing?
Regulation of gene expression in response to fluctuations in cell population density
How does quorum sensing work?
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
Give examples of quorum sensing molecules and the type of bacteria they are produced by.
AutoInducer-2 (AI-2) = Gram negative and positive bacteria
N-acyl homoserine lactones (NAHLs) = Gram negative bacteria
Competence signalling peptides = Gram positive bacteria
How can quorum sensing affect Candida albicans?
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
What is a digestive consortium and why do they arise?
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
Give an example of a digestive consortium.
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
What are accessory pathogens?
Commensal microbes that can support or enhance the virulence of a different organism
What is the minimum number of species usually required to form a dental abscess?
6-8
How does P. gingivalis contribute to microbial subversion?
Produces gingipain which degrades C3
Manipulates neutrophils by blocking TLR and phagocytosis pathways
Inhibits macrophage responses by blocking TLR4 signalling and iNOS production
How does Tannerella forsythia contribute to microbial subversion?
Produces karilysin which degrades C4
What helps some “unculturable” species to survive in enviroments?
Helper strains
