Project:
Klebsiella pneumoniae is considered a ubiquitous multi-host pathogen, however:
- A huge diversity of STs (> 5000) and genomic sublineages (~1800 currently) exists;
- The huge diversity of Kp in all sources investigated so far has limited our understanding of transmission across niches, as recent transmission is nearly impossible to observe;
- Not all sublineages (ST, clones) are host-generalists. For example, HvKp sublineages are sometimes found in carriage but seldom in environment or food;
- There is a paucity of genomic data originating from sources other than the human host (e.g., domestic and wildlife animals, the environment and water, food), which prevents a better understanding of their role in pneumoniae ecology and infections, leading to an incomplete evolutionary picture. This is due to a lag of Klebsiella studies with a ‘One Health’ focus, compared to clinical studies.
To better understand Kp transmission across niches, a new ‘One Health’ approach to Kp research is needed. This will be achieved either by: i) sampling Kp at niche interfaces (e.g., food versus human carriage in controlled settings); or ii) by focusing on known host-generalist clones (sublineages) with sufficient sampling in several niches to attain statistical significance in GWAS studies and to observe niche jumps through phylogenetic approaches.
Recent One Health studies have revealed a huge diversity of Kp sublineages in several sources, including nosocomial infections, human carriage, food, soil and animal carriage or clinical infections. Notable exceptions are peculiar types of infection such as liver abscess or rhinoscleroma.
However, a few sublineages stand out for having a higher prevalence in multiple niches compared to most sublineages.
Among these are i) sublineage 45 (SL45), defined by cgMLST, which comprises ST45, ST485 and ~10 other related STs; and ii) SL37. A few hundred genomes of SL45 from different sources have been sequenced. The phylogenetic analysis of these isolates shows a mix of sources across the phylogeny, including within a genetically homogeneous sub-branch of ST45 genomes.
Here, we propose to investigate the SL45 sublineage as a model of generalist lineage of Kp and, more generally, of multidrug resistant (MDR) ubiquitous bacteria. The objectives are: (1) to decipher ecological adaptations by comparing isolates from different niches, including the environment, animal and human carriage and clinical infections; and (2) To evaluate/model the flux of SL45 isolates across the various niches.
The strategy will include:
- Analysis of currently available genomes and metagenomes, as pilot datasets;
- Development of a rapid identification or selective enrichment method to improve the efficiency of future sampling of ST45 in multiple niches;
- Leverage on currently existing international networks to gather large SL45 collections;
- Decipher SL45 dissemination at various spatial scales, and across niches, along with the genetic adaptations to these.
- Demonstrate the functional role of GWAS hits in ecological adaptation in experimental models using mutants (laboratory work).
Profile: Young researcher with PhD, strong experience in evolutionary genomics and microbiology. Good command of scientific communication including writing publications and international oral communication
Environment. The job will be hosted within the Brisse group at Institut Pasteur, Paris, France. The project manager will work under the supervision of S. Brisse and in close contact with other members of the group. Availability of benchwork space and bioinformatics resources of Institut Pasteur. Interactions with an international group of collaborators.
Salary and contract. The monthly salary will correspond to the standards in France and will depend on the candidate’s experience. This is a fixed term contract for 24 months. The position is available in October 2022 or slightly later, depending on the chosen candidate’s availability.
Application. Please send your application as a single pdf file to Sylvain Brisse (sbrisse@pasteur.fr) with a detailed CV, a cover letter and references.
Deadline. September 30th, 2022. But please apply earlier if possible for you.