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Scientists discover the way to a new generation of antibiotics

antibiotic resistance

Antibiotic resistance is becoming a common occurrence. Once isolated, more and more we are turning away from the traditional antibiotics to our so called “last line of defense” antibiotics to fight infections. Sadly, in a growing number of cases these antibiotics are having less of an effect. However, new research reveals the mechanism by which drug-resistant bacterial cells maintain a defensive barrier.

The findings pave the way for a new wave of drugs that kill superbugs by bringing down their defensive walls rather than attacking the bacteria itself. It means that in future, bacteria may not develop drug-resistance at all.

Unravelling this mechanism could also help scientists understand more about human cell dysfunctions linked to disorders such as diabetes, Parkinson’s and other neurodegenerative diseases.

The team investigated a class of bacteria called ‘Gram-negative bacteria‘. These bacteria are particularly resistant to antibiotics because of its cells’ impermeable lipid-based outer membrane.

“All Gram-negative bacteria have a defensive cell wall. Beta-barrel proteins form the gates of the cell wall for importing nutrition and secreting important biological molecules.”

“Stopping the beta-barrel assembly machine from building the gates in the cell wall cause the bacteria to die.”

Researchers studied the gram-negative bacteria E.coli, in which the beta-barrel assembly machinery contains five subunits – known as BamA, BamB, BamC, BamD and BamE. They wanted to know exactly how these subunits work together to insert the outer membrane proteins into the outer membrane or cell wall.

The research looked at the whole beta-barrel assembly machinery structures in two states – the starting and finishing states. They showed that five subunits form a ring structure and work together to perform outer membrane protein insertion using a novel rotation and insertion mechanism.

“The beta-barrel assembly machinery is absolutely essential for Gram-negative bacteria to survive. The subunit BamA is located in the outer membrane and exposed to the outer side of the bacteria, which provides a great target for new drugs.”

“In Human mitochondria, a similar complex called sorting and assembly machinery complex (SAM) is responsible for building the outer membrane proteins in the outer membrane of mitochondria.”

“Dysfunction of mitochondria outer membrane proteins are linked to disorders such as diabetes, Parkinson’s and other neurodegenerative diseases, so we hope that this work may also help us to better understand these human diseases too.”

While this offers a real glimpse at a future where antibiotic resistance has been halted, taking a completely different approach and looking at the host (in this case us humans) to determine ways to prevent and stop bacterial infections might give us not only a way to reduce antibiotic resistance, but also a way to prevent bacterial infection all together.

Maybe we can go more indepth about that next time. But for now, this may be the key to fighting antibiotic resistance that researchers are looking for.

Gu, Y., Li, H., Dong, H., Zeng, Y., Zhang, Z., Paterson, N., Stansfeld, P., Wang, Z., Zhang, Y., Wang, W., & Dong, C. (2016). Structural basis of outer membrane protein insertion by the BAM complex Nature DOI: 10.1038/nature17199

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