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

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

lots of characteristics that can create clusters, not evolutionary consistent but a method of taxonomy nonetheless

used to build the phylogeny, tell us about evolutionary relatedness

phenotypic predictions based on the presence of virulence and resistance determinants

all other epidemiological and clinical metadata. abundance data.

used WGS, other molecular methods, contact tracing, social network analysis

super spreader = single source responsible for a large number of cases

an average number so does not reveal anything about the pattern of spread

R0 = 3 may mean all infected individuals infect three other people

persisted in working as a cook, exposing others to the disease - was forcibly quanrantined

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)

circulating viruses give rise to new variants that escape prior immunity against infection, immunity builds against these new variants, then these in turn spawn new variants

tend to emerge in australian winter and migrate to northern hemisphere for our winter - we get a bit of a heads up

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

lots of strains are given st numbers - refers to legacy technique from before the capacity for wgs

st stands for sequence type and is derived from multi locus sequence typing (used prior to wgs)

genes chose typically encode core metabolic enzymes (housekeeping genes) as these are likely to be under stabilising selection

with advent of wgs you tend to group similar variations together in one strain

longer distance transmission which creates more distinct strains

emerged in Birmingham area from a methicillin susceptible population of st22 by the acquisition of a type IVh SCCmec cassette

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

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

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

epidemiological and experimental evidence for increased virulence and transmissibility of ST239 within hospitals

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

how to measure mutation rate (and hence date of emergence) and

things close on the tree are close bc they have more snps in common

homoplasy - same things happening independently on different branches

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

many homoplasmic mutations observed in the Sars-CoV2 genomes that have a role in immune evasion and/or increased transmissibility

combines human and veterinary medicine in response to zoonoses

fear is that hospital adapted clones will also adapt to life outside of hospitals

have to consider all strains emerging from places like wastewater treatment plants or evolving due to agricultural methods

a joint initiative of the food and agriculture organisation of the un, the un environment programme, the world organisation for animal health, and WHO, collectively known as the quadripartite

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?

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

the means by which bacteria can move from one compartment to another is limited. seems unlikely

different strains are adapted to specific niches, and they are unlikely to thrive or expand in the wrong niche

the ecological and evolutionary dynamics are very complex, but have direct relevance to one health

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

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?

carbapenemase genes have been reported in the environment on almost every continent

considering te contribution of various sources to asymptomatic carriage of these genes within the community

source attribution model on a large aggregated dataset on the prevalence of these genes in the Netherlands from 2005-2017

conclusion that two thirds of the cases of acquisition of these AMR genes by the community reflects spread from within the community itself - do not dismiss the contribution of other sources such as food, animal contact and the enivornemnt (particularly water)

without input from non human sources the rate of transmission (R0) would not be sufficiently high within the community for these genes to be maintained. this implies that it should in principle be possible to mitigate the seemingly inexorable spread of AMR genes

limited evidence of transmission of strains between animals and humans

limited evidence of the transfer of resistance genes between animals and humans

however the livestock and human samples were not exact like fro like - they were sampled from different places at different times

whether for multi host bacteria such as s aueus, horizontally transferred genes follow the distribution of the bacterial cell that harbor them or create their own distribution

WIDESPREAD GENE SHARING BETWEEN BACTERIAL STRAINS COLONIZING DIFFERENT ANIMAL HOSTS