麻豆传媒

German E. coli deaths show it鈥檚 time to look past the wonder drugs of the 1950s in the battle against lethal bacteria

IN THE last month, bacteria have killed at least 22 people in Germany and made well over 2000 ill. There is a suspicion that they may have caught the bug from bean sprouts.

But this is no exotic invader, it is Escherichia coli, ubiquitous in our guts, our cattle and our labs. It is the most recent bug to evade normal screening methods and standard forms of treatment, and it won鈥檛 be the last. So perhaps the time has come to look past antibiotics 鈥� the wonder drugs of the 1950s 鈥� and find new weapons in the fight against superbugs.

No commonly used method of detection would have prevented the German outbreak. The lethal strain probably came originally from cattle, and was transmitted in the manure used to grow foods including seeds for bean sprouts. But even a recently introduced vaccine that stops cattle shedding toxic E. coli would have left it untouched, while standard tests for toxic E. coli in food would have missed it. Proposed US food rules about E. coli do not, yet, apply to it.

The outbreak confirms what have been saying for years: we ; the discovery of new classes of antibiotics; strategies to slow the growth of antibiotic resistance; faster diagnosis of infection and better ways to screen food.

The German strain belongs to a family of E. coli that clings to gut walls, but usually caused such mild disease 鈥� until now 鈥� that it is largely unstudied. It recently picked up a gene that causes bloody diarrhoea, putting it in a group known as Shiga-toxin E. coli (STEC).

鈥淭he German strain has until now caused such mild disease that it is largely unstudied鈥�

The hybrid was unprecedentedly lethal: Shiga toxin can cause severe kidney damage by inducing a disease called haemolytic-uraemic syndrome (HUS), but the German strain appears to be four times as likely to cause HUS as other STEC strains.

The strain also resists 鈥� although this point is of little relevance as most antibiotics can鈥檛 be used on STEC strains. That鈥檚 because the bacteria respond by producing more toxin, in a defence reaction called SOS.

However, two strategies used in the current outbreak point to future remedies. Some antibiotics don鈥檛 elicit the SOS reaction, and doctors in Germany are now , called carbapenems, against the outbreak strain.

They are lucky it doesn鈥檛 resist them. Last week the reported a 鈥渟harp increase鈥� in abdominal infections that resist carbapenems, including those caused by E. coli.

This underscores our desperate need for new antibiotics, says David Hooper of Harvard Medical School in Boston. Drug companies have largely abandoned the search, he says. There is little profit in short-term treatments. New models for drug discovery are needed, such as public-private partnerships, he says.

Besides antibiotics to kill bacteria, we need anti-toxins that block their effects. Doctors in Germany are successfully using a monoclonal antibody, originally developed to treat a rare genetic disorder, to block the immune response Shiga toxin stimulates to cause HUS.

We need more therapies aimed at toxins, says Stephanie Schuller at the University of East Anglia in Norwich, UK. For example, a drug that stops a toxin moving from gut to blood would be useful, though to be used in time this would also require earlier, more accurate diagnosis than is usual.

Another possibility is to vaccinate against toxins. There are efforts to develop a vaccine for the toxin made by Clostridium difficile, says Hooper. 鈥淲e could also vaccinate for Shiga, or the bacterial toxins that cause toxic shock. But those conditions are rare, so who should we vaccinate?鈥�

Stuart Levy of Tufts University in Boston thinks such treatments could focus on people facing hospital bacteria, the most likely to be antibiotic-resistant. He has developed small molecules that block the bacterial MAR gene, a 鈥渕aster switch鈥� that not only enables bacteria to cause disease but also activates antibiotic resistance. 鈥淭he drug will prevent disease until bacteria are dealt with by the immune system or just go through the gut,鈥� he says. Because they aren鈥檛 killed, there should be no drug-resistant survivors.

鈥淥ne drug stops bacteria causing disease while they are dealt with by the immune system鈥�

Still, people are unlikely to take such drugs just so they can eat bean sprouts. One option may be to vaccinate the cattle that carry E. coli. The vaccine Econiche immunises cattle against a group of proteins called the type three secretion system (TTSS), which is used by the most common cattle-borne STEC to invade the gut wall. The vaccine cuts the quantity of bacteria shed by infected calves and could also block other TTSS-equipped bacteria, such as Salmonella. Unfortunately, the German bug doesn鈥檛 use TTSS.

Policy changes could also have an effect. In the US, Representative Louise Slaughter has just introduced a bill to ban antibiotic growth promoters in cattle which evoke antibiotic resistance of the same kind seen in the German E. coli. Its chances of becoming law may now have risen.

Another ploy could be to chase the bacteria off our food. Keith Warriner of the University of Guelph in Ontario, Canada, says bacteria that live in the guts of herbivores have evolved ways to infiltrate bacterial communities on the plants herbivores eat. In some cases 鈥� notably bean sprouts 鈥� plant growth folds them into their tissues, so washing does not remove them.

Warriner has found that an old remedy 鈥� phage, a virus that attacks only bacteria 鈥� will kill Salmonella andE. colion vegetables. A preparation claiming to do this is in the US, but is little used. One reason for this is that phage doesn鈥檛 destroy all its hosts, and this is needed if you are to purify food.

Warriner has come close, by spraying vegetables with phage combined with harmless bacteria that displace the interlopers. But he has no funding to continue the work, and a pharmaceutical firm has lost interest. He hopes the German outbreak will change that.

The final hope is administering phage to kill bacteria in people. Work on this was abandoned in the west with the advent of antibiotics, but continued in the Soviet Union. A is currently testing a phage that also packs a protein which, like Levy鈥檚, shuts down bacterial DNA.

Levy, Hooper and others say phages are potentially useful. But we need to develop all possible antibacterial weapons far more urgently, they say. The bacteria are not waiting to attack us.

Since this article was first posted, the phrase 鈥淎 more practical option鈥� in the paragraph beginning 鈥淪till, people are unlikely鈥� has been replaced with 鈥淥ne option鈥�, and the phrase 鈥渘otably bean sprouts鈥� has been added to the paragraph beginning 鈥淎nother ploy鈥�.