BBC_Knowledge_2014-06_Asia_100p

TIMELINE

The fight against bacterial infection

We are now in what is known

as the post-antibiotic era,

which means that we haven’t got

enough antibiotics that are effective

against all of the types of bacterial

threats that are coming at us. The

antibiotic resistance genes are often

found on plasmids that function like the

USB stick of the bacterial world. The

systems that this research is looking at

are the means by which those USB

sticks are passed from cell to cell,

spreading the resistance genes to

new bacteria.

It’s not so much that the work is

going to revolutionise our under-

standing of antibiotic resistance, but

this is the first moment when we

understand the details of the

conjugation system [the transfer of

DNA], the three dimensional structure

and how it is all working. It’s a beautiful

molecular mechanism. Obviously,

years down the line, the idea is that we

will be able to control and block the

whole thing. At the moment we’ve just

got something to start working with.

It’s like a blueprint.

Furthermore, these DNA transfer

systems are not just important in

antibiotic spread, they are also the

system we use for genetically

engineering plants. When GM plants

are created, genes with the desired

traits are selected, isolated, and put

into a plant. So there may also be

future implications for researchers

improving those plant genetic

engineering systems as well. The more

we understand about the system, the

better we can exploit it.

Associate Professor in Microbiology

at the University of Nottingham

a bacterium’s cell envelope – the outermost

area of the cell. As well as enabling bacteria to

distribute genetic material among themselves, it

plays a crucial role in secreting toxins in infections

causing ulcers, whooping cough, or severe forms

of pneumonia such as Legionnaires’ disease.

“The entire protein complex [through which

type IV secretion takes place] is huge and its

structure is unprecedented,” said project leader

Gabriel Waksman. “This is ground-breaking work

and will provide an entirely new direction to the

field. Next, we need to understand how bacteria

use this structure to get an idea of how antibiotics

resistance genes are moved around.”

The team was able to reconstruct the system

as observed in the bacteria Escherichia coli using

electron microscopy. The mechanism consists

ANALYSIS

Prof Cath

Rees

of two separate complexes, one in the outer

membrane of the cell and the other in the inner

membrane. They 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 bacteria’s secretion system

could help design new compounds able to

stop the secretion process, thereby stopping

the spread of antibiotic resistance genes,” says

Waksman. “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.”

PHOTO: GABRIEL WAKSMAN/UCL/BIRKBECK INSTITUTE, THINKSTOCK X2, PRESS ASSOCIATION

A computer model of the

structure through which

secretions are able to pass

from the inner to the outer

membrane of a bacterium

Outer membrane

Inner membrane

The pioneering

surgeon Joseph Lister

begins researching the

phenomenon that

urine-contaminated

mold could inhibit the

growth of bacteria.

1871 1928 1943 1961

Sir Alexander Fleming

discovers that the

bacterium

Staphylococcus aureus

can be destroyed by

Penicillium notatum, a

kind of mold.

Just four years after

pharmaceutical

companies began

mass-producing

penicillin, microbes

begin appearing that

could resist it.

MRSA (methicillin-

resistant Staphylococcus

aureus) is detected in

Britain for the first time

and goes on to become

an increasing problem

in hospitals.