Interview with Dr Claire Chewapreecha: Tropical disease, sequencing, and evolution.

I’d like to welcome Dr. Claire Chewapreecha from the University of Cambridge. And she’s going to talk to us about bacterial pathogenesis. Claire, tell us about yourself. Well, I’m originally from Bangkok, Thailand. I’m interested in mining the genomes of the bacteria. And recently, I’ve been very fortunate to be awarded Sir Henry Wellcome Fellowship. So this allows my research activities in Thailand and UK. And could you tell us more about your work? I work on a particular tropical disease called melioidosis. I’m not sure you’ve heard of the name. Well, most people don’t. But this disease is a public health burden in tropical countries. And the known hot spots for the disease is Northeast Thailand and Northern Australia.

But our global understanding of the disease epidemiologic changed recently as the microbiology infrastructure improved. And this expanded the endemic zones to the rest of Southeast Asia to South Asia, part of Africa, and also in the Central and South America. The disease is caused by the bacterium called Burkholderia pseudomallei. And most of the patients, they are farmer working in the rice paddy field. And they can acquire the bacterium through inoculation, ingestions, or inhalations. The mortality rates are very high, though. In Thailand, about 40% of cases died. And that’s even with treatment. With untreated patients, we estimate that the mortality rate could reach 90%. And currently, there’s no vaccines available. And what is Burkholderia pseudomallei. That’s quite a wordy species name.

This is a Gram negative bacterium. So this bacteria occupy wide ranges of host niches. It’s live in soil and contaminated water. And it can survive in plants, in mammals, and in human host. And how has genome sequencing improved our understanding about this bacteria? Genome sequencing helps massively. For this particular bacterium, Burkholderia pseudomallei, it has a huge genomes, two chromosomes at least and a combined size of roughly seven to eight megabase. So you can imagine that there’s a lot of genes and a lot of inflammations in there.

This combined with the fact that the bacteria occupy wide ranges of host niche, so we hypothesised that some of the subsets of genes might allow the bacterium to adapt and to colonise in particular niche, including human host. And how did you identify the genes that influence disease potential? That’s a very important question. So we thought that some of the genes or genetic variations within this pathogen might allow part of them to be better adapted to human infection. So we used a technique called genome by association study. That is to mine the genomes for the prevalence of particular genes or genetic variations that are more prevalent in clinical isolates versus environmental isolates.

And we are very fortunate because there’s a lot of genomes already available in the public database. So that’s power our studies. So we managed to identify some potentials virulence candidate. However, computational analysis alone wouldn’t be adequate. We need some experimental validation to back up our hypothesis. However, it is quite tricky because Burkholderia pseudomallei is highly virulent. And it’s categorised under category three. So we need spatial lab containment to perform experiments involving these organisms. And such facilities is not available everywhere. So to avoid that issue, we use another species, which is closely related, but less virulent called Burkholderia thailandensis as a proxy. And in order to do so, we mine the genomes of Burkholderia thailandensis for homologous genes.

So that’s why blast search through the NCBI database. And once we identified that, we can knock out and manipulate the genes in Burkholderia thailandensis to investigate what we found. How variable are these genes? Very, very variable. And one of the interesting features that we saw is that there seems to be a strong geographic signals. That is, genes, virulence candidate (genes) detected in Thailand is quite different from what we’ve seen in Australia. So I think we need to mine the data further, so in this sense, we need more information. And how does your research translate to public health? I think a good understanding of basic biology is key to inform a better choice of treatment.

And from what we found so far in the genomes, we saw a lot of diversities between different geography. And that suggests that there’s not going to be any one rule that fit all, in terms of choice of treatment and also vaccine. So vaccine design needs to take into account of bacterial diversity, geographically, and also, in some cases, even locally. Thanks again, Claire. This was really fascinating. My pleasure. Thank you so much.