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Exploiting intra-species diversity to identify genomic properties that affect the cell biology, proliferation and pathogenicity of Klebsiella pneumoniae

Project description

Decoding a deadly pathogen’s hidden strengths

Klebsiella pneumoniae bacteria are responsible for infections such as pneumonia, urinary tract infections and wound infections, and the pathogen is associated with around 600 000 deaths a year. This drug-resistant bacteria tops the WHO’s bacterial priority pathogen list. However, besides known resistance mechanisms, the knowledge of the bacterium’s biology still lacks many details. Supported by the Marie Skłodowska-Curie Actions programme, the KLEBSCELL project intends to address this issue via studying the effect of the extensive genetic variation of Klebsiella pneumoniae strains on their growth, survival and virulence properties. This will be achieved using a methodological approach involving large-scale cellular imaging, comparative genomics and genetic engineering of a wide collection of strains.

Objective

Klebsiella pneumoniae is an opportunistic pathogen that can cause particularly serious disease and mortality in immune-compromised, elderly, or otherwise vulnerable individuals. A high burden of mortality is attributed to K. pneumoniae: a 2019 study estimated that K. pneumoniae was associated with 790.000 deaths that year. Due to its incidence, mortality, and growing antibiotic resistance, the World Health Organization placed K. pneumoniae at the top of the Bacterial Priority Pathogens List in 2024, highlighting its danger to public health. Despite the high healthcare burden posed by K. pneumoniae, it remains a rather understudied pathogen, particularly regarding non-canonical virulence factors. Antibiotic resistance, for example, is rather well-studied in the pathogen, but our understanding of K. pneumoniae physiology, including the keys to its growth, replication, and survival in diverse environments is limited. K. pneumoniae displays extensive intra-specific diversity, with its pangenome encoding close to 30.000 protein-coding sequences. The general goal of this proposal is to exploit the extensive intra-species diversity of K. pneumoniae to determine how specific genomic properties affect cellular physiology, contribute to growth and proliferation, and underlie pathogenicity. The functional role of selected regions will subsequently be determined in more detail. K. pneumoniae intraspecific diversity will be investigated using a library of 100-200 strains across different growth conditions and antibiotics. A high-throughput cell imaging system will be used to collect various phenotypic measures. Next, genomic studies will uncover genetic differences among the strains, and these differences will be connected to phenotype. Finally, genetic manipulation will be used to confirm the effect of these genetic differences. Such knowledge about the pathogen’s genetic components for success is important in managing K. pneumoniae infections more effectively in the future.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

(opens in new window) HORIZON-MSCA-2025-PF

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Coordinator

KATHOLIEKE UNIVERSITEIT LEUVEN
Net EU contribution
€ 200 400,00
Address
OUDE MARKT 13
3000 Leuven
Belgium
Region
Vlaams Gewest Prov. Vlaams-Brabant Arr. Leuven
Activity type
Higher or Secondary Education Establishments
Links
Total cost
No data