- Scientists in the US may have found a
new way to combat bacterial infection in the fight against diseases that
kill millions worldwide.
- It might even provide an alternative
to antibiotics which are becoming less effective as bacteria develop resistance
to our most successful drugs.
- The scientists from the University of
California in Santa Barbara (UCSB) say they have identified a "master
switch" that controls the genes in microbes which make them infectious.
- Their studies focused on Salmonella typhimurium,
a bug that causes severe stomach upsets and even death. By manipulating
a special enzyme, the researchers were able to "turn off" the
danger genes, in effect "disarming" the bacterium.
- But the microbe, although incapable of
spreading disease, still provoked a strong immune response that was highly
effective against subsequent infections, making it an ideal live vaccine.
- Immunised mice survived
- The enzyme is called DNA adenine methylase,
or Dam for short. It is essential for the development of Salmonella-related
illness because it regulates the expression of at least 20 genes necessary
- The UCSB team's experiments, reported
in the journal Science, show that Salmonella bacteria containing a mutated,
or altered, form of Dam fail to produce the proteins that would normally
make the bugs virulent.
- They injected 17 mice with the Dam-mutant
bacteria and then challenged them with high doses of Salmonella typhimurium.
All 17 mice survived the challenge while an unimmunised control group of
mice all died.
- When they took a closer look, the researchers
found that the "disarmed" bacteria grew in the mucus lining the
intestines but could no longer invade or colonise other areas of the gut.
- "The bacteria are completely disabled
in their ability to cause disease, and these crippled bacteria work as
a vaccine since they stimulate immune defences against subsequent infections,"
says Professor Michael Mahan, one of four scientists in the Santa Barbara
- Drug-resistant pathogens
- Significantly, the Dam "master switch"
is not confined to salmonella - it exists in many other infectious bacteria,
including those which cause cholera, plague, typhoid, dysentery, meningitis
and E.coli poisoning.
- Currently, microbial infections are the
leading killer worldwide, responsible for 17 million deaths each year.
The researchers believe their discovery will be a major aid in the fight
against newly emerging, drug-resistant pathogens.
- "When it comes to bacterial disease,
the wake-up call has been sounded," says Professor Mahan. "Our
microbial defences are crumbling as superior pathogens have emerged that
can no longer be controlled by available antibiotics.
- "There are numerous warning signs
including the recent emergence of drug resistant tuberculosis, Staphylococcus,