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

Environment

Transmission

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.

Ongoing project

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 wgsa.net).

Project partners

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

The emergence of antibiotic resistant bacteria represents a severe threat to global public health, and there is an urgent need to identify new strategies to mitigate the spread of these infections. Improved management of antibiotic resistance requires deep knowledge of both the evolution and ecology of these pathogens. The use of antibiotics in agriculture and aquaculture means that environmental niches can act as incubators for the emergence of new resistant strains. It is therefore critical that we understand how these bacteria adapt and survive under many different and varied conditions, including in soil, in water and in animals.

The aim of this project is to identify the environmental settings which pose the gravest risk to public health, with respect to the emergence of antibiotic resistance. We target a group of closely related bacterial species called Klebsiella, which includes the species K. pneumoniae. This species is one of the most common infectious agents in hospitals, and has acquired resistance to a wide range of antibiotics. We have sampled thousands of Klebsiella strains from humans, animals, soil and water in and around a single town, Pavia, in northern Italy. By applying modern genome sequencing techniques to these strains, we will begin to understand where in the environment new resistant bacteria might be evolving, and how they spread from one place to another, which will ultimately help to manage their spread.

Project resources

Publications

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