This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Antimicrobial resistance is one of the world's top public health threats. Often termed a silent pandemic, antimicrobial-resistant bacteria have caused millions of deaths annually.
If left unchecked, the number of deaths attributed to antimicrobial-resistant bacteria is expected to increase to 10 million a year by 2050, according to estimates by the World Health Organization. NTU scientists are pioneering strategies to stay one step ahead of these bacteria. One NTU research team developed a compound that inhibits an enzyme crucial for energy generation in a resistant bacterium.
Collaborating with the Agency for Science, Technology and Research in Singapore (A*STAR), another group of researchers from NTU's Lee Kong Chian School of Medicine (LKCMedicine) uncovered how the same bacterium resists infection by viruses. To understand how another resistant bacterium colonizes its host, a research team from NTU and Imperial College London investigated the molecular structure of the 'weapon' it uses to load and fire toxins into rival bacteria and other cells. Their research has opened avenues for new treatments that target antimicrobial-resistant bacteria, as well as novel ways of disarming such bacteria.
Opportunistic pathogens that are resistant to antimicrobials are especially concerning because they infect patients with weakened immune systems. For instance, Mycobacterium abscessus causes severe lung disease in patients with cystic fibrosis and is intrinsically resistant to many commonly used antibiotics. To treat M. abscessus infections, a team of researchers led by professor Gerhard Grüber of NTU's School of Biological Sciences (SBS) has developed a compound that prevents the bacterium from generating energy for survival.
The compound inhibits a key enzyme in the electron transport chain of M. abscessus, a series of proteins that the bacterium uses to produce adenosine triphosphate (ATP), a molecule that cells use to power their metabolic processes. The findings are published in Nature Communications. Using cryo-electron microscopy, the scientists identified a pocket in the cytochrome b subunit of the cytochrome bcc oxidase, a crucial enzyme in the electron transport chain of M. abscessus, that binds to the substrate and is responsible for the enzyme's activity.
They then designed a compound that fits into the pocket to inhibit the enzyme. Because the structure of the cytochrome bcc oxidase is unique to M. abscessus, the compound targets only the bacterium and is not toxic to human cells. When used in combination with clofazimine, an antibiotic used to treat mycobacterial infections, the new compound was effective at killing M. abscessus (2-log fold reduction in four days).
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