Identification and characterization of infecting Leptospira interrogans strains traditionally rely on the successful isolation of the bacterium from the blood of infected humans or animals. However, the success rate of blood culture isolation is generally very low, largely because patients and animals often receive antibiotic treatment prior to sample collection. This reduces bacterial viability and proliferative capacity, frequently resulting in culture failure.
To overcome this limitation, we aim to develop an approach enabling the direct sequencing of Leptospira genomes from clinical samples, despite the overwhelming presence of host (human or animal) DNA. The project will explore the use of Oxford Nanopore adaptive sampling technology, combined with either targeted Leptospira DNA enrichment or host DNA depletion strategies, to selectively increase the proportion of Leptospira reads during sequencing.
This approach will enable culture-independent genomic characterization of infecting strains, providing valuable insights into pathogen diversity and outbreak investigations while significantly reducing the biases associated with bacterial isolation procedures.