Research: LKCMedicine-led study proposes a new way to look at infections

By Amanda Lee, Senior Assistant Manager, Media

An international research team led by LKCMedicine Assistant Professor Sanjay Haresh Chotirmall has proposed a new way of understanding infections.

Their study of close to 400 respiratory samples from patients with bronchiectasis, a chronic lung condition, has shown that microbes in the body exist as a network. The researchers also discovered that an infection’s severity could be a result of interactions between these microbes.

These findings were published in one of the world’s leading scientific journals, Nature Medicine, in April. The study brings scientists one step closer in developing a new way of tackling infections, by targeting microbial interactions rather than the specific microbes. 

Asst Prof Sanjay, who is also NTU Provost’s Chair in Molecular Medicine, said the findings of the study are the first steps in providing a more holistic view of how infections occur.

While the study looks at patients with bronchiectasis, Asst Prof Sanjay said the concept may apply to all forms of infections such as skin or gastrointestinal infection.

“We are therefore proposing that microbes exist as networks, where interactions happen between them. We can potentially improve clinical outcomes by breaking such crosstalk,” he added.

The interdisciplinary team includes researchers from Singapore’s NTU LKCMedicine, Tan Tock Seng Hospital, Changi General Hospital, and Singapore General Hospital; the University of Malaya in Malaysia, Italy’s Fondazione IRCCCS Ca’ Granda Ospedale Maggiore Policlinico and the University of Milan; the University of Sydney in Australia; the University of Dundee in Scotland; and the University of Exeter in the UK.

For their study, the researchers looked at patients with bronchiectasis, a disease of high Asian prevalence, where airways dilate irreversibly and, where infection promotes progression.

To investigate interactions between microbes in the airways of patients with bronchiectasis, the team collected respiratory (sputum) samples from Singapore, Malaysia, Italy, and Scotland, including samples before, during and after bronchiectasis flare-ups.

After analysing the genetic material from bacteria, fungi and viruses in the samples, the researchers assessed for possible microbial interactions and found that patients with frequent flare-ups had more negative interactions, where microbes compete rather than cooperate, and that the number of such negative interactions increased even further during a flare-up.

While changes to interactions between microbes during flareups was detected, there was minimal change to the type and quantity of microbes present during a flare-up, and even after antibiotics were administered.

The researchers believe the findings suggest that microbial interactions potentially drive frequent flare-ups in patients.

Using these findings, the scientists have developed an online tool to help other researchers and physicians analyse microbial interactions in their own patient samples through the microbes’ genetic sequences.

The study also allows researchers to be more focused in their antibiotic use. “Thus, for the next phase of our study, we will be conducting clinical trials to see the effect of antibiotics on microbial networks in the context of clinical trials,” said Asst Prof Chotirmall.