ScienceNot yet confirmed elsewhere1 publisher2 min readPublished
NTU designs a compound that cuts off a resistant lung bacterium's energy supply
NTU scientists built a compound that starves Mycobacterium abscessus of energy; paired with the drug clofazimine it cut the microbe a hundredfold in four days. Two other teams mapped the same bacterium's virus defenses and a related pathogen's toxin-firing weapon.
The Scientist · Science desk
What happened
- Mycobacterium abscessus, the bug two of the teams went after, causes severe lung disease in people with cystic fibrosis and resists many first-choice antibiotics on its own.
- Grüber's group used cryo-electron microscopy to pinpoint the substrate-binding pocket in the cytochrome b subunit of the energy enzyme, the spot that drives its activity.
- That enzyme is built differently in M. abscessus than in people, so a compound shaped to its pocket hits the bacterium without poisoning human cells, the team reports.
- A separate NTU team, working with Singapore's A*STAR, worked out how M. abscessus fends off bacteriophages, reporting it in the Proceedings of the National Academy of Sciences.
- A third team, with Imperial College London, mapped the structure of the apparatus a different resistant bacterium uses to fire toxins into rival microbes and host cells.
Why it matters
- capability Resolving the enzyme down to its binding pocket gives chemists a defined shape to design a molecule against. That is how the team reached this compound.
- constraint The reported result came only when the compound was combined with an existing antibiotic, so any treatment built on it would be given alongside other drugs.
- decision Knowing how M. abscessus survives phage attack changes how phage therapy would be designed, aiming to clear the infection without breeding fresh resistance.
The enzyme the compound shuts down sits in M. abscessus's electron transport chain, the protein relay the microbe uses to make ATP, the molecule that powers its metabolism. [5] The team designed a molecule to fit the enzyme's binding pocket and switch it off. [8]
"As the currency of life, ATP delivers the energy for essential processes in M. abscessus, including its defense mechanisms against antibiotics," said Gerhard Grüber of NTU's School of Biological Sciences, the study's corresponding author. "Silencing the electron transport chain that produces ATP is thus a potential treatment for difficult-to-treat M. abscessus infections that also disables the bacterium." [10][4]
The study is published in Nature Communications. [6] It reports the kill as a two-log reduction, a drop of about a hundredfold. [9][17] The account does not say whether that was measured in a culture dish or in an animal. A patent has been filed, and the team is working with the U.S. company Hsiri Therapeutics to license the compound, the only one of the three findings with a drug candidate behind it. [11]
The second target is how the bacterium survives viruses. Bacteriophages break into bacteria, hijack their replication machinery to copy themselves, and burst the cell open. Because that cycle kills the host, phages have been proposed as a therapy for M. abscessus. [12] The bacterium comes in two forms: a smooth variant coated in lipids called glycopeptidolipids that grows round colonies, and a rough variant that lacks the coat, grows cauliflower-shaped colonies, and causes more severe disease. [15]
Each of the three studies mapped a specific structure inside a resistant microbe and found a route to block it: the energy enzyme's binding pocket, the phage defenses of M. abscessus, and the toxin-firing apparatus of a related pathogen. [4][13][16]
The World Health Organization estimates that resistant infections, already blamed for millions of deaths a year, could kill 10 million a year by 2050 if left unchecked. [1][2]
What to watch
- Whether Grüber's compound clears M. abscessus in animal studies, since the reported result is a four-day combination test.
- The outcome of the Hsiri Therapeutics licensing talks and whether the compound enters formal preclinical development.
- Whether the NTU-Imperial toxin-apparatus structure translates into a specific way to disarm the pathogen it came from.
Clarity's read
What the record supports and how the coverage leans. The claims behind it follow.
Reality
- Evidence42
- Adoption8
- Hype gap+25
- Incentives55
- Confidence38
Claim ledger
Ranked by verification strength, evidence, and original report placement.
- [1]
Antimicrobial resistance is one of the world's top public health threats, often called a silent pandemic, and antimicrobial-resistant bacteria have caused millions of deaths annually.
- [2]
If left unchecked, deaths attributed to antimicrobial-resistant bacteria are expected to rise to 10 million a year by 2050, according to World Health Organization estimates.
- [3]
Mycobacterium abscessus causes severe lung disease in patients with cystic fibrosis and is intrinsically resistant to many commonly used antibiotics.
- [4]
A team led by Professor Gerhard Grüber of NTU's School of Biological Sciences developed a compound that prevents Mycobacterium abscessus from generating the energy it needs to survive.
- [5]
The compound inhibits a key enzyme in the electron transport chain of M. abscessus, the series of proteins the bacterium uses to produce ATP, the molecule cells use to power their metabolic processes.
- [6]
The energy-compound findings are published in Nature Communications.
- [7]
Using cryo-electron microscopy, the scientists identified a substrate-binding pocket in the cytochrome b subunit of the cytochrome bcc oxidase, a crucial enzyme in the electron transport chain, that is responsible for the enzyme's activity.
- [8]
The researchers designed a compound that fits into the pocket to inhibit the enzyme.
- [9]
Used in combination with clofazimine, an antibiotic used to treat mycobacterial infections, the compound killed M. abscessus with a 2-log fold reduction in four days.
- [10]
As the currency of life, ATP delivers the energy for essential processes in M. abscessus, including its defense mechanisms against antibiotics. Silencing the electron transport chain that produces ATP is thus a potential treatment for difficult-to-treat M. abscessus infections that also disables the bacterium.
ReportedSupportedSource: Gerhard Grüber, NTU School of Biological Sciences, corresponding author of the studyView cited source - [11]
A patent has been filed, and the researchers are working with U.S.-based pharmaceutical company Hsiri Therapeutics to license the compound.
- [12]
Bacteriophages are viruses that infect bacteria and hijack their replication machinery to make copies of themselves until the bacteria burst and release new viruses, and they have been explored as a possible treatment for M. abscessus infections.
- [13]
In a study in the Proceedings of the National Academy of Sciences, researchers from NTU and Singapore's Agency for Science, Technology and Research (A*STAR) uncovered how M. abscessus resists attack by bacteriophages.
- [14]
The phage findings shed light on how phage therapies can be optimized to treat M. abscessus infections effectively while minimizing the development of resistance.
- [15]
M. abscessus exists as a smooth variant, which produces lipids called glycopeptidolipids and forms round colonies, and a rough variant, which lacks glycopeptidolipids, forms cauliflower-shaped colonies, and causes more severe disease.
- [16]
A team from NTU and Imperial College London investigated the molecular structure of the weapon a resistant bacterium uses to load and fire toxins into rival bacteria and other cells.
- [17]
A 2-log reduction is a factor of 10 squared, about a hundredfold fewer bacteria.
- [18]
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.
Sources
1 independent publisher whose own reporting we read for this story.
- phys.orgEnergy production, virus defenses and toxin loading emerge as vulnerabilities in resistant bacteria
1 article · October 3, 2026
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Topics
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Entities
- Nanyang Technological UniversityFollow
- Gerhard GrüberFollow
- Pablo BifaniFollow
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- Pseudomonas aeruginosaFollow
- ClofazimineFollow
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- Imperial College LondonFollow
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