The system that allows the sharing of genetic material between
bacteria - and therefore the spread of antibiotic resistance - has
been uncovered by a team of scientists from UCL and Birkbeck,
University of London.
The study reveals the mechanism of bacterial type IV secretion,
which bacteria use to move substances across their cell wall. As
type IV secretion can distribute genetic material between bacteria,
notably antibiotic resistance genes, the mechanism is directly
responsible for the spread of antibiotic resistance in hospital
settings. It also plays a crucial role in secreting toxins in
infections - causing ulcers, whooping cough, or severe forms of
pneumonia such as Legionnaires' disease.
The work, led by Professor Gabriel Waksman at the Institute of
Structural and Molecular Biology (a joint UCL/Birkbeck Institute)
revealed that the type IV secretion system differs substantially
from other bacterial secretion systems, in both its molecular
structure and the mechanism for secretion.
Professor Waksman said: "This work is a veritable tour de force.
The entire complex is absolutely huge and its structure is
unprecedented. It is 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."
Using electron microscopy the team were able to reconstruct the
system as observed in the bacteria E. coli. They saw that the
mechanism consists of two separate complexes, one in the outer
membrane of the cell, and the other in the inner membrane, which
are connected by a stalk-like structure that crosses the periplasm
- the space between the two membranes. The complexes at both the
inner and outer membranes form pores in the membrane, via which
substances can be secreted.
Understanding the structure of the secretion system will help
scientists uncover the mechanism by which it moves substances
across the inner and outer membranes. It could eventually help
scientists develop 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 cells.
Professor Waksman said: "Understanding bacteria's secretion
system could help design new compounds able to stop the secretion
process, thereby stopping the spread of antibiotics resistance
genes. Given that antibiotics resistance has become so widespread
and represents a grave threat to human health, the work could have
a considerable impact for future research in the field of
antimicrobials."
The paper, Structure of a type IV secretion system, is published inNature.