Energy production, virus defenses and toxin loading emerge as vulnerabilities in resistant bacteria
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.
The research conducted by scientists from Nanyang Technological University (NTU) in Singapore reveals vulnerabilities in resistant bacteria that can potentially be exploited for new treatments. A compound developed by NTU researchers inhibits an enzyme crucial for energy generation in a resistant bacterium, preventing its survival.
This compound, which targets a unique pocket in the bacterium's cytochrome bcc oxidase enzyme, shows promise in treating Mycobacterium abscessus infections, a severe lung disease that often resists antibiotics. The compound was found to be effective in combination with clofazimine, resulting in a significant reduction in M. abscessus within four days.
Researchers also studied how M. abscessus resists viral attacks, identifying mutations in genes responsible for the synthesis and transport of glycopeptidolipids, which are used by bacteriophages to infect and destroy the bacteria. This discovery could help optimize phage therapy treatments by using a combination of bacteriophages targeting both smooth and rough variants of M. abscessus to minimize resistance development.
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