A new generation of antibiotics

Researchers from the University of East Anglia (University of East Anglia, UK) approached the problem of antibiotic resistance. A new study published in the journal Nature, reveals the mechanism by which antibiotic-resistant bacteria cells support a protective barrier.

The obtained results open the way for a new wave of drugs hitting superbugs, destroying their protective cell wall and not attacking microorganisms. This means that in the future, bacteria in General may cease to develop resistance to antibiotics. Disclosure of this mechanism may also contribute to the study of disorders in human cells associated with diseases such as diabetes, Parkinson’s disease and other neurodegenerative diseases.

Research group, supported by the Foundation Wellcome Trust (UK), used the synchrotron Diamond Light Source to study gram-negative bacteria. Diamond emits intense light emission brightness is 10 billion times greater than the sun that allows scientists to investigate almost any material with precision to atoms.

Gram-negative bacteria are particularly resistant to antibiotics (compared with gram-positive) due to the presence of the additional outer membrane of the cell wall. This membrane protects the cells from attack by the human immune system and antibiotics, allowing a pathogenic bacteria to survive. But the removal of this barrier makes the bacteria vulnerable and leads to death.

The research team has previously found the “Achilles heel” of the outer membrane, however, until recently it was not known how this protective barrier is constructed and maintained.

“Multiple resistance of bacteria to drugs, also known as antibiotic resistance is an international public health problem. Many modern antibiotics are becoming useless, causing hundreds of thousands of deaths annually. The number of superbugs is increasing at an unexpected rate,” says lead researcher Professor Cancian don (Changjiang Dong) from the Medical School Norwich (Norwich Medical School) at the University of East Anglia.

“Gram-negative bacteria are among the most difficult to control because of the high resistance to antibiotics. All gram-negative bacteria have an additional protective membrane. Beta cylindrical proteins form the “gates” in the membrane for import of nutrients and the secretion of important biological molecules. The Assembly machinery of beta-cylinders (beta-barrel assembly machinery, the BAM) is responsible for the construction of the gate membrane. Stopping leads to the death of the bacteria,” explains don.

The researchers investigated gram-negative bacterium E. coli, in which the Assembly machinery of beta-cylinders consists of five subunits – BamA, BamB, BamC, BamD and BamE. A research group was interested in how these subunits work together, embedding other membrane proteins in the outer membrane or cell wall.

“We solved the complete structure of the Assembly machinery of beta-cylinder in two States – initial and final. We found that the five subunits form a ring structure, and are working to embed the proteins in the outer membrane with the use of a new mechanism of rotation and insertion. Our work is the first to describe a BAM complex, which opens the way to designing drugs of new generation. BAM is absolutely necessary for the survival of gram-negative bacteria. Subunit BamA is located on the outer membrane and is open to influence and can become a good target for new drugs”, says Professor don.

“In the mitochondria of person a similar complex is called complex machinery of sorting and assembling (sorting and assembly machinery complex, SAM) and is responsible for the construction of proteins of the outer membrane in the outer membrane of mitochondria. Dysfunction of the proteins of the outer membrane of mitochondria are associated with diseases such as diabetes, Parkinson’s and other neurodegenerative diseases, because we hope that this work will help to find new approach to the study of human diseases,” explains the researcher.