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New insight into bacterial drug resistance

By Tim Sandle     Oct 9, 2016 in Science
Researchers are investing time and resources trying to understand how pathogenic bacteria function, in a quest to find new ways to inhibit and kill the disease causing organisms.
As an example of this, scientists from University of Leeds have found a protein complex of interest. The complex is called BAM and it is referred to “beta-barrel assembly machinery.” This complex is found in association with many types of Gram-negative bacteria (of which several are pathogenic.) The complex functions to insert other proteins, including those that have a protective function, into a bacterium’s outer cellular layer. It is the through the outer membrane of the bacterial cell that most bacteria are protected from environmental stresses.
These same proteins play an important part in helping form a barrier across the outer cell membrane to protect bacteria from antibiotics. An understanding of how the protein complex operates has come about through the use of advanced X-ray crystallography together with electron microscopes. The imaging was undertaken using the Diamond Light Source, which forms part of the U.K.'s synchrotron science facility. The advanced imaging center is based at the Harwell Science and Innovation Campus in Oxfordshire.
With a new understanding of the BAM protein and how it functions, researchers are hopeful they will be able to design a new generation of antimicrobial drugs. In a research note, one of the lead researchers, Professor Neil Ranson explains “this is a complex molecular machine involved in keeping bacteria alive, and we know that mutations in it are lethal to the bacteria. Some beautiful work by other labs has shown that BAM exists in two different shapes -- an open and closed form -- but the open form seemed to require part of the complex to fall apart.”
The main focus on a new generation of drugs will seek to stop the BAM complex from operating. Studies suggest that if the BAM complex is rendered inoperable then bacteria cannot survive an assault of antimicrobial drugs. It could be possible to achieve this by disrupting just one protein in complex.
Such work is important given the diminishing number of effective antimicrobial drugs available and the rise in antimicrobial resistant strains of disease causing bacteria.
The research has been published in the journal Nature Communications. The research paper is titled “Lateral opening in the intact β-barrel assembly machinery captured by cryo-EM.”
More about antimicrobial resistance, Bacteria, Infection, Antibiotics
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