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





Research Project: 2017-05-01 - 2020-12-31
Total sum awarded: €1 865 784

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. In order to control the spread of Kp through targeted surveillance and intervention policies it is necessary to identify the sources of emergent community and health-care associated infection from the interlinked and varied niches encompassing “the environment”. To address this, we will sample from multiple clinical, community, agricultural, veterinary and environmental settings in and around a single town, Pavia, in Northern Italy, and supplement these data with matched samples from France and elsewhere. We will use whole genome sequencing of community (mixed-colony) samples to assay accessory gene abundance and distribution. This contrasts with the more common approach based on phylogenetic analysis of single colonies, which would be of limited utility over broad environmental scales due to the complexity of transmission chains, environmental dormancy, and high rates of recombination. In contrast, our gene-centric approach provides a much more efficient means to understand ecological adaptation, the distribution of resistance and virulence genes, and to identify key environmental reservoirs from which clinical clones emerge. A key deliverable of this project will be the establishment of a pan-genome database (‘pangenomium’) that will integrate with both existing Kp genome community resources established by project partners (BIGSdb-kp, and

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  • Edward Feil, University of Bath, United Kingdom (Coordinator)
  • Piero Marone, IRCCS Fondazione Policlinico San Matteo, Italy (Partner)
  • Sylvain Brisse, Institut Pasteur, France (Partner)
  • Louise Matthews, University of Glasgow, United Kingdom (Partner)
  • Jukka Corander, University of Oslo, Norway (Partner)
  • David Aanensen, Big Data Institute, University of Oxford, United Kingdom (Partner)
  • Alan McNally, University of Birmingham, United Kingdom (Observer)

The rise of antimicrobial resistance is a pressing public health crisis on a global scale, but the use of antibiotics in humans only represents a small part of the problem. Effective management strategies need to incorporate antibiotics in agriculture, as well as the release of these drugs, and resistant bacteria, into the environment. This project conforms to this “One-Health” framework by discovering how frequently antibiotic resistant bacteria move between humans, animals and different settings in the environment such as river water and soil. The project focusses on a group of bacterial species called Klebsiella which are common in the environment and in animals, but also cause infections in humans and livestock that are resistant to antibiotics. One species in particular, K. pneumoniae, is a very common cause of resistant infections in hospitals and is recognised by the WHO as critically high priority. Northern Italy is a ‘hotspot’ for these infections, but it is not clear whether these bacteria are confined to hospitals, or are also present elsewhere. To address this, we took 3500 Klebsiella strains from hospital patients, wild and domesticated animals and multiple environmental sources. Importantly, all the strains were taken from a single city, Pavia, in Lombardy. By sequencing the genomes of these bacteria, combined with mathematical modelling, we could tell which resistant genes were present, and how the strains were moving. We found that resistant genes are strains were uncommon outside of hospitals, and that the vast majority (around 75%) of Klebsiella in humans comes from other humans. However, we did find some risk of transmission from companion animals (dogs and cats) and water sources.