快猫短视频

THE antibiotic-resistant bacteria running riot in hospitals could soon meet
their match. Researchers in California say it may be possible to make the most
dangerous bugs vulnerable to antibiotics again.

Staphylococcus bacteria have become a serious problem in hospitals because
they have evolved systems to defeat many antibiotics. Tens of thousands of
patients become infected every year, and doctors are running out of new
antibiotics to treat them. The most effective weapons used in the past,
penicillin and related drugs called beta-lactams, have long been useless against
these superbugs.

Beta-lactams work by targeting the proteins that help reinforce bacterial
cell walls. Without this reinforcement, the wall easily ruptures and the
bacterium dies. But staphylococci have learnt how to fight back. They make a
protein called beta-lactamase that inactivates beta-lactam antibiotics.
Producing these anti-drug proteins is a burden, however, so the bacteria make
them only when they are needed.

In resistant bacteria, a repressor protein called BlaI normally blocks
expression of the beta-lactamase gene. Meanwhile, a protein in the bacterium鈥檚
cell wall, called BlaR1, keeps watch for beta-lactam antibiotics. If it detects
any, it inactivates BlaI, allowing production of beta-lactamase to begin. But
despite three decades of study, biologists had not been able to figure out how
this signalling process works.

Now Hong-Zhong Zhang, Henry Chambers and their colleagues at the University
of California, San Francisco, have discovered that staphylococci use a
signalling system hitherto unknown in the bacterial world. Instead of chemically
modifying the target proteins by attaching small molecules to them, both the
sensor and regulatory protein are physically cut or cleaved. 鈥淲e didn鈥檛 expect
that,鈥� says Zhang. 鈥淚t was a big surprise.鈥�

The researchers discovered this unique signal by tagging BlaI and BlaR1 to
make them easy to detect. They found that when BlaR1 senses antibiotics, it
snips itself, changing to a form that triggers the slicing of BlaI. 鈥淭hey鈥檝e put
the pieces together very nicely,鈥� says Joseph Bosilevac of the Virginia
Commonwealth University in Richmond.

Zhang and his colleagues are now looking for industrial partners to help them
find drugs that will 鈥渂lind鈥� the sensor protein BlaR1, so BlaI isn鈥檛 destroyed
and the bacteria remain vulnerable to antibiotics. If the approach works,
Bosilevac thinks it could be used to thwart other antibiotic resistance systems.
His team already has unpublished evidence that a second antibiotic resistance
pathway also involves a series of protein cleavages.