Mechanism of antibiotic resistance revealed
7 Apr 2014 by Evoluted New Media
Antibiotic resistance represents a serious threat to human health, and researchers in London have taken an important step towards understanding how it spreads by unravelling a bacterial secretions system.
Bacteria use type IV secretion to move substances across their cell walls; the system – which can distribute genetic material between bacteria – differs substantially from other bacterial secretion systems in both its molecular structure and mechanism of secretion. The mechanism is directly responsible for the spread of antibiotic resistance in hospital settings, and plays a crucial role in secreting toxins in infections, causing ulcers, whooping cough and severe forms of pneumonia.
Researchers from University College London (UCL) and Birkbeck, University of London used electron microscopy to reconstruct the system as observed in E. coli. The mechanism consists of two separate complexes – one in the outer membrane of the cell and the other in the inner membrane. The two are connected by a stalk-like structure that crosses the periplasm, the space between the two membranes. The complexes at both membranes form pores in the membrane through which secretions are made.
“This work is a veritable tour de force,” said Professor Gabriel Waksman from the Institute of Structural and Molecular Biology, a joint UCL/Birkbeck Institute. “The entire complex is absolutely huge and its structure is unprecedented.”
“It’s the type of work which is ground-breaking and will provide an entirely new direction to the field. Next we need to understand how bacteria use this structure to get a movie of how antibiotics resistance genes are moved around.”
Understanding the structure of the secretion system will help scientists reveal how cells move substances across the inner and outer membranes. It could also help in the development of new tools for the genetic modification of human cells, as the bacteria could act as a carrier for genetic material which could then be secreted into the cells.
“Understanding bacteria’s secretion systems could help design new compounds able to stop the secretion process, thereby stopping the spread of antibiotics resistance genes,” said Waksman. “Given that antibiotics resistance has become so widespread and represents a grave threat to human health, the work could have considerable impact for future research in the field of antimicrobials.”
