Block 4 - Pathogens Flashcards
(39 cards)
Discuss the initial difficulties of classifying microbes.
Classifying microbes initially challenging due to size, they were first classified by shape. Advances in biochemistry, metabolism and microscopy enabled the detection of the presence of;
- Spore formation
- Aerobic conditions
- Cell staining results
- Motility
Discuss gram-staining in bacteria.
Bacteria can be classified as:
* Gram-negative
* Gram-positive
* Variable
The Gram stain procedure differentiates bacteria into Gram-positive (purple) and Gram-negative (pink/red) based on cell wall structure, using crystal violet, iodine, decolorization, and safranin.
Gram-positive bacteria are bacteria that give a positive result in the gram stain test.
Gram-negative bacteria are bacteria that give a negative result in the gram stain test.
“Variable bacteria,” specifically “gram-variable bacteria,” refers to bacteria that do not consistently stain as either Gram-positive or Gram-negative during the Gram staining process, showing a mixed pattern of pink and purple cell.
Discuss which types of bacteria are gram-negative.
o Bacillota, mycoplasmatota and actinmyocetota are all gram-negative.
Bacillota (Firmicutes) – bacillales, clostrida and lactobacillales.
Mycoplasmatota (mycoplasma).
Actinmyocetota (actinobacteria) – actinomycetaceae and bifidobacteriaceae.
Describe which types of bacteria are gram-positive.
o Pseudomonadota are all gram-positive.
Alphaproteobaceria – rhizobiales and rickettsiales.
Betaproteobacteria – neisseriales.
Gammaproteobacteria – enterobacteriales.
Epsilon-proteobacteria – camplyobacterales.
Define the term microbiota.
Microbiome is often used in the literature to mean the population of microorganisms at a specific location however the term should now be microbiota.
Describe how the different microbiotas can be anaylsed.
The most widely used method is to perform amplicon sequencing of the 16S rRNA gene for bacteria and the ITS for fungi. Microbiota studies are based on ecological principles which are used to ;
- Describe individual samples (alpha diversity)
- Compare samples (beta diversity)
Additional ‘omics’ technologies can be applied to the same sample to understand the ecosystem further.
Describe alpha diversity.
Alpha diversity is a measure of how diverse a sample is based on:
* How many species there are (richness)
* How abundant each species are (evenness)
Within a sampled environment.
Describe beta diversity.
Beta diversity is a measure of how different (or similar) two samples are to each other.
Discuss dysbiosis.
An imbalance in the bacterial composition in a given ecological niche. Typically seen as:
Loss of beneficial bacteria.
Overgrowth of potentially pathogenic bacteria.
Loss of overall bacteria diversity.
Often associated with negative consequences.
Outline factors potentially affecting the microbiota.
Genetics
Air pollution
Antimicrobials
Medications
Diet
Stress
Chemicals
Pathogens
Early life experience
Describe the human microbiota.
Originally estimated ratio of bacteria to human cells was 10:1. Sender, Fuchs and Milo now estimate number of bacteria in a 70 kg “reference man” to be 3.8x10^13, human cells in a 70 kg “reference man” are estimated to be 3.0x10^13. Bacteria to human cell ratio is approximately 1:1, total bacterial mass is approximately 0.2 kg.
Describe the human microbiota project.
Funded by the NIH 2007-2016, HMP1 300 healthy individuals.
Up to 3 points.
Nasal passages, oral cavity, skin, gastrointestinal tract and urogenital tract.
16S rRNA sequencing to identify core healthy microbiome, metagenomic whole genome shotgun sequencing for functions and pathways.
Describe the integrative human microbiome projects (HMP2).
Three studies on dynamic changes in the microbiome and host:
- Pregnancy and preterm birth
- Inflammatory bowel disease
- Stressors that affect individuals with prediabetes
Describe the gut microbiota.
The most well characterised human microbiota.
Bacteria in the gut can:
Help rejuvenate host tissue
Inhibit inflammation
Metabolic complex carbohydrates
Synthesises of vitamins
Impact of obesity
Discuss the skin microbiota and acne.
Skin microbiota consist of anaerobic, aerobic and facultative bacteria.
Approximately 10^4 – 10^5 bacteria/sebaceous gland. Beneficial roles of the skin microbiota include:
* Promoting epithelial tight cell junction expression
* Immunomodulation
* Secretion of antimicrobial peptides
Increased hormonal activity during puberty stimulates oil production in the sebaceous gland. Cutibacterium acnes degrades sebum triglycerides and results in inflammation.
Describe viruses.
Viruses are not ‘alive’ but are obligate intracellular parasites that infect all forms of life. They are unable to replicate outside of host cells.
Outline the steps in the viral life cycle.
1) Recognition
2) Attachment
3) Fusion / Penetration
4) Uncoating
5) Transcription
6) Protein Synthesis
7) Replication
8) Assembly / Envelopment
9) Lysis and release / Budding and release
Define the latent and eclipse periods in viral infection.
The latent period is the time before an increase in intracellular virus.
The eclipse period is the time before an increase in extracellular virus.
[see supporting diagram]
Describe the general patterns of infection.
- Acute infection -> a short duration, high severity infection.
- Persistent infection -> a very long duration, high severity infection.
- Latent, reactivating infection -> a short duration, varying severity reoccurring infection.
- Slow virus infection -> a short but relapsing high severity infection.
[see supporting diagram]
Discuss herpes simplex & VZV latency.
1) Primary infection.
Herpes simplex = mild pharyngitis fever.
Varicella = chicken pox.
Virus transit up peripheral nerve, latent virus in sensory neuron in dorsal root ganglion of the spinal cord.
2) Recurrence.
Herpes simplex = cold sore.
Varicella = zoster (shingles).
Age and X-irradiation (act via depressed CMI), local injury or infection (e.g. sinusitis) activates the virus in the neuron.
Outline the determinants of viral disease.
- Target tissue
Portal of entry
Access of virus to target tissue
Tissue tropism of virus
Permissiveness of cells for replication - Viral pathogen (strain)
- Immune status
Competence of the immune system
Prior immunity to the virus - Cytoplasmic ability of the virus
- Immunopathology
- Virus inoculum
- General health of the individual
- Genetic make-up of individual
- Age
Outline the factors in viral epidemiology. (spread of disease)
o Critical community size
o Mechanisms of virus transmission
Respiratory or salivary spread.
Formities (e.g. tissues, clothes).
Sexual contact.
Zoonoses (animals, insects [arboviruses]).
Blood transfusions, organ transplant, needle sharing (common in drug abusers).
o Geographical/Season
Presence of cofactors or reactors in environment.
Habitat and season for arthropod vectors.
School/Universities session; close proximity.
Climatic conditions.
Outline the 3 main controls of virus diseases.
1) Public health care
2) Vaccination
3) Chemotherapy
Outline the difficulties of designing an anti-viral drug.
1) Few biochemical pathways unique to viruses.
2) Therapeutic index often very low.
3) Selection of drug resistant mutants.
4) Many viruses which cause similar diseases have very different modes of replication and may not be sensitive to some drugs.
5) By the time symptoms appear often chemotherapy is too late to make much difference to clinical course of disease.