Lecture 23 Flashcards
What is a mycobacterium and how are they typically grouped?
Mycobacterium is a genus of Actinobacteria, it includes many important pathogens and over 40 species (such as tuberculosis and leprosy), all of which have a characteristic thick cell that is hydrophobic and waxy. They are typically grouped into either fast-growing (within 7 days) or slow growing (after 7 days) and some can be very difficult to culture and can mean that genetic manipulation is poor, this means a lot can be learnt from genome sequencing.
What is Mycobacterium ulcerans and what is infection linked to?
Mycobacterium ulcerans is a slow growing (1 division in 48 hours) necrotising infection of the skin and soft tissues, it is endemic in tropical regions and painless, meaning it is often left untreated until very late. It is linked to proximity to slow moving or stagnant water and environmental damage. It is associated with amoebae, aquatic plants, algae and snails which feed on these. Transmission is thought to be majorly via an insect vector and there is little evidence of person-person transmission.
What are some major differences and genomic differences between M.ulcerans and M.marinum?
ulcerans is slow growth with mycolactone, no pigments, not many niches, extracellular disease. Marinum is fast (4-6 hours) no mycolactone, pigments, more niches, acts as a frog and human macrophage (mainly frogs), leading to skin dermal lesions intracellularly.
Genomic differences include: Mycolatone is encoded on M ulcerans on large plasmid (via horizontal gene transfer), reproductive evolution led to smaller genomic size for ulcerans, many more pseudogenes in ulcerans, ulcerans has hundreds more insertion sequences etc.
How is mycolactone produced by ulcerans? What did it require for this in it’s evolution?
M. ulcerans all acquired a 174 kb plasmid encoding for mycolactone production (kills cells and stops immune system). The mycolactone is primarily produced via extremely large protein assembly lines (they have many active sites on the one protein, which will pass the products on). The acquisition of this pMUM001 was followed by divergence of strains that can cause disease, these divergent strains over time lost non essential genes from their old environment.
What is the homology like between M.ulcerans and M.marinum? Why?
At the nucleotide level M.ulcerans and M. marinum have 98% homology yet there have been many changes due to the much larger number of Insertion sequences in ulcerans. These inactivate genes and lead to rearrangements, insertions and deletions.
What does reciprocal recombination between invert repeat insertion sequences or transposons do?
Reciprocal recombination between invert repeat Insertion sequences or transposon elements will invert the DNA sequences between them. This can lead to lower expressed genes.
What are PE and PPE family proteins? Which has less?
PE and PPE family proteins are characteristic N-terminal motifs unique to mycobacteria, they are cell surface proteins with virulence and host range or immune evasion function. Ulcerans had less of these than marinum. Possibly because Ulcerans has mycolactone.
What is a pseudogene?
PE and PPE family proteins are characteristic N-terminal motifs unique to mycobacteria, they are cell surface proteins with virulence and host range or immune evasion function. Ulcerans had less of these than marinum. Possibly because Ulcerans has mycolactone.
