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genomic epidemiology - Coggle Diagram

- - - - can lead to pneumonia, wound, soft tissue and urinary tract infections
      - tend to be more resistant as exposed to abs as selective pressure
    - - tends to be more virulent
      - can lead to pyogenic liver abscess, pneumonia, meningitis
      - causes commercially important livestock disease eg. bovine mastitis
  - - - Kp can carry beta lactamases (broad and extended spectrum with lactamase inhibitors)
        
        CTX-M
        
        SHV
        
        TEM
    - - most important mechanism of carbapenem resistance is the production of carbapenemase enzymes
        
        kpc
        
        ndm
        
        vim
        
        oxa-48
      - carbapenemase genes associated with a small number of widespread kp clones, mostly responsible for hospital-acquired infections
        
        ST258/512
        
        ST307
        
        usually carried on plasmids
        
        no carbapenemase genes isolated outside of healthcare settings and very few in species other than k pneumoniae (isolates were not selected for resistance)
      - burden of carbapenem resistant k pneumoniae increased by a factor of 6-16 times in terms of number of infections and number of deaths, between 2007 -> 2015
  - - - gene clusters associated with heightened virulence
      - seems the more individual genes the strain has the more virulent it is
        
        access to iron is critical for pathogenicity
        
        yersiniabactin
        
        aerobactin
        
        salmochelin
        
        colibactin (toxin)
      - the regulators of mucoid phenotype
        
        rmpA
        
        rmpA2
        
        both up regulate capsule production
      - hypervirulent lineages contain all 4 siderophores plus rmpA and rmpA2 eg. CG23 in Kp
        
        associated with community-acquired infection resulting in liver abscesses
  - - - 477 of 682 (69.9%) carbapenemase-positive isolates are concentrated in four clonal lineages, sequence types 11, 15, 101, 258/512 and their derivatives
    - - non resistant plasmid found in sampling nowhere near any carbapenem resistant outbreaks
      - could transfer easily into a bug
      - cryptic resistance gene - biding its time before it transfers and is able to confer resistance
    - - isolates from a single hospital are phylogenetically divergent
      - carbpenemase producing isolates show strong geographical structure, and tend to correspond to a single major clone within hospital or local region
- - - - surveilllance
      - interventions
      - transmission
        
        accessible methodologies to identify sources and drivers of AMR between one health sectors
        
        impact of infection prevention and control practices on mitigating AMR
        
        how does AMR transmission across one health sectors in HICs vary from LICs/LMICs? and according to antibiotic/pathogen?
      - economics and policy
      - behavioural insights
  - - - is this flow impended by ecological barriers? that is, does local adaptation limit to the competitiveness of migrants entering a new setting or niche?
      - understanding which of these routes is the most important is key
      - not just opportunity, but capability and likelihood - ecological dimensions
      - eg. how much are bacteria found in pigs adapted to pigs vs. adapted to survival in humans
    - - opportunity
        
        the means by which bacteria can move from one compartment to another is limited. seems unlikely
      - ecology
        
        different strains are adapted to specific niches, and they are unlikely to thrive or expand in the wrong niche
      - a key example of ecological adaptation is specialisation to different hosts
        
        spillover refers to when a pathogen jumps from one host to another
        
        could be a single sporadic with no onward transmission and little risk
        
        alternatively, inter host transmission might result in the bacteria spreading within the new host
        
        greater levels of host specialism may reduce the chance of successful spillover
        
        the ecological and evolutionary dynamics are very complex, but have direct relevance to one health
        
        host specialism
        
        interactions between species
        
        phylogenetic distance between host species
        
        environmental factors
        
        source host factors
        
        recipient host factors
        
        intermediate host factors
        
        characteristics of the pathogens
        
        transmission opportunity, ecology, use of antibiotics. setting-specific drivers (eg. animal husbandry, wastewater treatment processes)
        
        sporadic transmission/infection of environmental strains
        
        cycling/enrichment of known high-risk AMR strains
        
        emergence and spread of novel AMR strains in the environment (most esoteric risk)
        
        how do we interpret data on the presence/absence of clinically important genes/strains in non clinical settings, with respect to risk, or the likelihood of these outcomes?
  - - - hospital and municipal wastewater
      - drinking water
      - natural waterways
      - sediments
      - recreational waters
      - companion animals
      - wildlife
      - agricultural environemnts
      - food animals
      - retail food products
  - - - recombination can play a key role in host adaptation
- - - - how quickly is the strain spreading and to what degree are local variants genetically distinct from each other?
      - how much mixture of stains do we see in one location eg. hospital
    - - when and where did a strain emerge?
      - how fast is it evolving (mutation rate)?
      - can we identify triggers leading to the emergence of a new virulent strain?
      - is there anything about the host population that might be naive or resistant to a particular strain?
    - - reconstructing the genetic events leading to the phenotypic changes underlying increased risk to public health
    - - conflict between what a strain IS and what its CAPABLE OF DOING
        
        lots of characteristics that can create clusters, not evolutionary consistent but a method of taxonomy nonetheless
        
        core genome
        
        used to build the phylogeny, tell us about evolutionary relatedness
        
        transmission dynamics
        
        outbreak source
        
        non core genome
        
        accessory genome
        
        what does it do
        
        how does it transmit
        
        is it resistant
        
        phenotypic predictions based on the presence of virulence and resistance determinants
        
        all other epidemiological and clinical metadata. abundance data.
      - examine an outbreak of tuberculosis in BC canada
        
        used WGS, other molecular methods, contact tracing, social network analysis
        
        found a link to a few users of crack cocaine - super spreaders
        
        super spreader = single source responsible for a large number of cases
  - - - given we know the period of infectiousness
    - - R0 = 3 may mean all infected individuals infect three other people
      - more likely most infected people infect 0 or 1 other people but a few super spreaders pass it on to many more
        
        particular settings where there were super spreader events
  - - - persisted in working as a cook, exposing others to the disease - was forcibly quanrantined
      - died after 30y in isolation
      - estimated to have infected at least 122 people including 5 dead
  - - - may cause more serious disease (have heightened virulence)
      - may be more difficult to treat or prevent (eg. resistance to antibiotics or vaccine escape)
      - may be more transmissible (eg. through increased rate of replication, or through better colonisation of the host, or survival outside of the host, such as on surfaces)
      - many homoplasmic mutations observed in the Sars-CoV2 genomes that have a role in immune evasion and/or increased transmissibility
    - - for bacteria, we can identify, for most key pathogenic species, particularly dangerous strains that have a high level of antibiotic resistance, or are highly virulent (high risk clones)
      - when one hiric replaces another it is called 'clonal' replacement
      - eMRSA-15 emerged in the uk, became the most rapidly spreading mrsa clone in europe
        
        emerged in Birmingham area from a methicillin susceptible population of st22 by the acquisition of a type IVh SCCmec cassette
        
        also acquired resistance to fluoroquinolones through two point mutations generating amino acid substitutions Ser8oPhe in topoisomerase IV (GrlA) and Ser84Leu in gyrase A (GyrA)
        
        co-incident with the first preclinical trials of fluoroquinolones in the same place
        
        acquired resistance to methicillin and then to fluoroquinolons (antibiotics given pre-surgery) - resistance to fq is probably what gave it such a high selective advantage
      - lots of strains are given st numbers - refers to legacy technique from before the capacity for wgs
      - major spread in early 2000 almost completely down to ST22 strain
        
        two different dynamics
        
        local spreading within one hospital
        
        longer distance transmission which creates more distinct strains
      - comet shaped phylogenetic tree = big explosion with tail of initial strain
    - - at its peak the most common mrsa strain - accounts for 90% of mrsa cases in mainland Asia and is also very common in South America and eastern europe
      - multiply resistant (exhibits a large SCCmec element) and is only found within the hospital environment
      - relates to concept of fitness cost
        
        see hospitals as an ecological niche, exposure to antibiotics, unique surfaces, routes of transmission through contact
        
        bacteria adapt to the niche, mrsa is a massively adapted bacterium
        
        mr is a massive gene that takes up a lot of the genome - lots of the consequences that come with it
        
        like a suit of amour in a medieval battle - great for the setting but very impractical anywhere else
        
        hence only being found in hospitals (specifically niche)
      - epidemiological and experimental evidence for increased virulence and transmissibility of ST239 within hospitals
      - wgs on a collection of 62 st239 isolates
        
        42 from europe, north and South America, Asia, Australia 20 year temporal range
        
        20 strains from a single hospital in northern Thailand collected over a single year
        
        examine global spread and potential for local epidemiology
        
        illustrates 2 concepts
        
        how to measure mutation rate (and hence date of emergence) and
      - of the 4310 sites exhibiting an SNP, 38 were homoplasmic, meaning they occurred independently on different lineages in the tree
        
        conflict with the tree
        
        tree is based on commonality of snps
        
        things close on the tree are close bc they have more snps in common
        
        homoplasy - same things happening independently on different branches
        
        what's going on - the mutation is random, it doesn't care, but selection does
        
        if a particular mutation confers a strong adaptive advantage and occurs independently, we're likely to see it at multiple points in the population
        
        notably many of the homoplasic saps were inn genes involved in drug resistance, with 10 corresponding to mutations known to confer resistance
  - - - tend to emerge in australian winter and migrate to northern hemisphere for our winter - we get a bit of a heads up
- - - - toxicity
      - adhesion
      - transmissibility
      - immune evasion
      - tissue specificity
- - - - when and where did the strain emerge?
      - how fast is it evolving (mutation rate)?
      - can we identify triggers leading to the emergence of a new virulent strain?
    - - reconstructing the genetic events leading to the phenotypic changes underlying increased risk to public health
      - the virulence/transmission trade-off is complex
        
        not necessarily the case that pathogens evolve to become less virulent
- - - - the majority of reports of convergence come from clinical settings in Asia, particularly china
      - convergence of virulent and resistance can arise through the presence of virulence and resistance plasmids in the same celll, or by the emergence of hybrid plasmids that carry both traits