Claire Chewapreecha: Melioidosis genomics
Genetic investigations into melioidosis, profiling both bacteria and patients, help understand disease acquisition and outcomes. Furthermore, identifying prevalent harmful bacterial genes supports vaccine development, and the development of CRISPR-Cas-based tests responds to an urgent need for rapid diagnosis that can reduce the detection time to under three hours with higher sensitivity. Applications developed in resource-limited settings show improved global applicability and impact on patients’ outcomes.
My name is Claire Chewapreecha. I am a Wellcome International Intermediate Fellow based at the Mahidol Oxford Tropical Research Unit in Bangkok, Thailand. I lead a team to investigate the genetic basis of a bacterial infection called melioidosis.
My research has been collecting and profiling the genetics of the bacteria that cause melioidosis, the bacteria that can be collected from patients' environmental exposures, as well as the genetics of the patients themselves. So, we're creating the database to try to investigate the genetic factors in both the host and the bacteria that influence the disease acquisitions, as well as the disease outcome.
One of the research highlights from our recently collected datasets is that we could identify the bacterial genes or alleles that are more prevalent in disease-causing isolates compared to environmental isolates. One of the top hits are genes that the bacteria use as needles to puncture and get into the host cells, and coincidentally, this gene, SCP1, has been already picked as a vaccine candidate. So, these examples highlight how genetic studies can support the vaccine's design, and the vaccine community seems to be quite pleased with the result.
The big question in the field right now is how we can speed up the disease diagnosis. Currently, the gold standard to diagnose melioidosis is the culture-confirmed approach, and this typically takes three to four days for the culture-confirmed result to arrive. However, within that waiting window, about 20% of patients die before they know they've got melioidosis. And for the patients who know they've got melioidosis, another 20% die within a month after admission. So, there's call for a demand to develop a rapid diagnostic test.
We have teamed up with local researchers to develop the CRISPR-Cas-based diagnostic, and this is based on the detections of nucleic acids of the bacteria. By using the genetic data that we've been collecting, we can identify the conserved regions as a target in the bacteria that are unique to the species that causes melioidosis, but cannot be identified in other species as well as the human host. Our CRISPR assays reduce the diagnostic time from three to four days to less than three hours, and currently, it has the highest sensitivities of any rapid test of up to 93%, as compared to 66% of the culture approach. We hope that it can be a game changer.
We strongly believe that with rapid diagnostic, we can identify patients faster, we can treat them with correct antibiotics faster, and we hope that that will help save more lives from melioidosis.
I think a direct impact to save lives is worth a lot of funding, but the other message I would like to deliver is that any technologies developed in resource-limited setting has its own advantages. It's not easy to develop something in resource-constrained settings, but when we operate in this area that forces creativity, and we have to decide our equipment to be very light. I strongly believe that any assays that are up and running in such setting can be operated anywhere in this world. And that's why we think it's worth funding.
I think we are very fortunate to be able to work in our current setting, even though it's resource-limited. But we connect to patients, we learn how they suffer from melioidosis, we learn the impact the disease had on their life, and we receive so many blessings from patients and relatives for the success of our research. And hopefully, that's helped improve their life.
This interview was recorded in January 2024