The rates and routes of transmission of multidrug resistant Klebsiella clones and genes into the clinic from environmental sources.

Klebsiella genuset representerar en heterogen grupp av bakteriearter som ofta finns hos människor, boskap, plantor, jordmån, vatten samt vilda djur. Många av arterna i gruppen är opportunistiska patogener som bär diverse former av antibiotikaresistensgener. K. pneumoniae står för en hög belastning av folkhälsa i många länder, speciellt på grund av snabb spridning av carbapenem-resistenta bakteriekloner. Därmed är Klebsiella av särskilt intresse för evaluering av risker förknippade med spridning av virulenta och resistenta kloner från djur och miljö till människor. Vi rapporterar här en analys av 6548 prover och 3482 genomsekvenser som täcker 15 olika arter av Klebsiella. Dessa samlades in under en 15-månaders period från diverse källor (sjukhus, jordbruk, miljö) inom den italienska regionen Lombardia. Trots att carbapenem-resistenta kloner cirkulerar frekvent inom sjukhusen, hittades inget belägg för spridning av denna typ av resistens utanför sjukhusmiljöerna. Den icke-slumpmässiga fördelningen av klonerna över olika källor stödjer hypotesen om ekologiska trösklar som förhindrar spridning av kloner mellan olika miljöer. Vi hittade evidens för sällsynta fall av transmission mellan djur och människor, men i den överväldigande majoriteten av kliniska fall härstammar infektionen från andra människor.

Due to the Covid pandemic data production in the project got delayed by 18 months and consequently all the planned main publications are correspondingly delayed. Data production was finalized on August 6, 2021, but the analyses for future publications will continue into 2022. The main scientific findings of the project so far are reported in the preprint https://www.biorxiv.org/content/10.1101/2021.08.05.455249v1 We found evidence for strong ecological barriers delimiting transmission of Klebsiella clones between animals, environment and human health care, which has implications for informing future One Health policy for some of the most urgent AMR priority pathogens classified by the WHO.

Klebsiella pneumoniae (Kp) is a leading cause of multidrug resistant hospital-acquired infections globally, and is responsible for an increasing public health burden in the community. Whilst there is an urgent need to mitigate the emergence and spread of Kp, this will only be possible with a detailed understanding of the forces underpinning the genetic and ecological diversity of this ubiquitous organism. Specifically, a broad ecological context is required to identify the sources of emergent community and health-care associated infection from the many and varied niches encompassing the environment, which will in turn inform on targeted surveillance and intervention policies. In order to address this, our primary methodology will be first to sample from multiple clinical, community, agricultural and environmental settings within a well-defined geographic locale, in and around a single town, Pavia, in Northern Italy. We will combine these samples with epidemiologically matched samples from elsewhere in Europe. We will then utilise whole genome sequencing (WGS) to characterise entire Kp communities from each setting. Pathogen WGS is being increasingly used for outbreak investigation, but these studies are based on single colony sequencing followed by phylogenetic analysis of the core genome. Excepting cases where the transmission chains are very short (eg from a cow to a farmer), the dynamics of transmission within the environment, and between the environment and the clinic, are far more intractable than within a single health care setting. Complex transmission chains, incomplete sampling, multiple co-colonising and co-transmitting strains, rapid movement of MGEs, and the extreme diversity of Kp will all limit the utility even very large datasets based on individual genome sequences for inferring broad transmission dynamics at this scale.