Antibiotic resistance – a threat to humanity

Researchers are working against the clock to resolve one of the biggest future problems facing the human race: antibiotic resistance, which the WHO has ranked as one of the world’s most serious health risks.

Without an effective antibiotic to rely on in the future, our situation would be catastrophic. Operations and even childbirth would involve major risks. In medical terms, we would be back in the Dark Ages.

Mate Erdelyi, Anne Farewell and Rosmarie Friemann are three researchers from the Department of Chemistry and Molecular Biology with one thing in common: antibiotics. They are members of different research teams with slightly different focuses, but everyone researching antibiotics has the same aim: finding ways to prevent antibiotic resistance.

MATE ERDELYI IS AN organic chemist, and his research team is trying to find ways to prevent bacteria from breaking down existing antibiotics.
“In developing countries in Asia, for example, animals are given antibiotics from birth and then throughout their lives,” says Mate. “Large quantities of antibiotics end up in the environment through animals’ urine and faeces, and so bacteria get used to the antibiotics. When we then come to use them, bacteria are already resistant.”

So one of the causes of antibiotic resistance is cattle being treated preventively with antibiotics to stop them becoming ill. This is not permitted in Sweden, but is common practice in countries such as China and the USA. Avoiding preventive treatment of animals with antibiotics could therefore have a major positive effect on preventing antibiotic resistance.

THERE HAS BEEN a significant rise in interest in antibiotic resistance over the last decade, and different approaches are now being taken in the work to combat the threat of resistance. Microbiologist Anne Farewell is investigating how antibiotics can be effectively transferred through biofilms, since it is hard for the antibiotic to penetrate the cell of the bacteria. Biofilms are bacteria that colonise a surface, such as tissue in the body, a prosthetic heart valve or a catheter.
“Many different methods are currently being trialled,” she explains. “We don’t yet know which method will be best. Other research collaborations deal with evolution, in other words how we can impede the development of bacteria. In an ideal world, we would give antibiotics against a specific bacterium and a medicine that prevents it from becoming resistant, thus impeding the bacterium’s evolution.”

Biochemist Rosmarie Friemann is currently involved with a number of international research collaborations, including in India, the USA and New Zealand.
“We’re studying transport proteins which, on inhibition, mean that the surface structure of the bacterium changes so that the immune defence can recognise the bacterium,” she says. “There are opportunistic bacteria that we carry around with us all the time, but that only come to life when we become ill.”

BACTERIA ARE VERY GOOD at camouflaging themselves in the body, including in biofilms.
“The system we’re looking at is involved in this camouflage process,” continues Rosmarie. “If we can block the biochemical path, the surface structure of the bacterium will be changed and our body’s immune defence will be able to deal with it.”

The three researchers believe that one solution may be using combinations of different antibiotics that work in different ways.
“If we attack the bacteria biochemically in different ways, there is less of a risk that they will be able to defend themselves,” says Anne. “If we only use one way, they can mutate much faster.”

IF DOCTORS ALSO GET better at investigating which bacteria cause a particular infection, this would improve the situation.
“Broad-spectrum antibiotics that tackle all bacteria in the same type are often used now,” explains Rosmarie. “We need to do a better job of quickly diagnosing which bacteria are the cause of the infection so that we can provide the right treatment straight away.”

NO NEW CLASSES OF antibiotics – new antibiotics that worked differently to the existing types – were developed between 1962 and 2000. Since then, only a handful of new classes have been developed, and most new types are simply a modification of existing antibiotics.
“There was a long period when no new antibiotics were created by the pharmaceutical companies,” says Anne. “We thought the problem had been resolved, and that it was just a case of producing more of the same. But that wasn’t the case. The problem of antibiotic resistance will always arise, and we will always need to develop new types of antibiotics.”

ONE PROBLEM IS THAT it is not profitable for pharmaceutical companies to invest in developing new antibiotics, since the development costs are the same as for a heart medicine that patients take every day for the rest of their lives. Another problem is resistance. If a new antibiotic is released in China, bacteria become resistant within a few months.
“The fact that antibiotics are constantly given to animals, combined with excessive prescription, means that they pass into sewage and end up everywhere,” Mate points out. “As a result, the bacteria learn to break down the antibiotics extremely quickly. This in turn means that the pharmaceutical companies are unwilling to spend large sums developing new medications that might be completely unusable within just a few years.”

THE EFFECTIVENESS OF a particular antibiotic depends on where in the world it is prescribed. If large quantities of the antibiotic have been used, the bacteria will have become accustomed to it. Penicillin still works reasonably well in Sweden, but not in India.

“Whatever we do in Europe, I don’t think it will have much of an effect,” continues Mate. “If we don’t solve the problem globally, we’ll just see resistance problems over and over again. We should also focus more on preventive work, on really finding out which antibiotics should be prescribed. And the entire hygiene mentality needs to change.”

ONE BIG PROBLEM in many developing countries is the approach to hygiene. The majority of infections that require antibiotics could probably be prevented through better hand-washing. Poor quality water and a lack of hygiene means that the proliferation of resistant bacteria is increasing. This makes it easy for antibiotic-resistant bacteria to spread among the population, which in turn means that new antibiotics are needed.
“We need to try to stay one step ahead, and find new cell mechanisms so we can trick bacteria into not surviving,” says Rosmarie.

In recent years, a number of studies from the biggest Swedish research councils have focused on antibiotic research.
“Things are different now compared with a decade ago,” concludes Anne. “Back then, no one was talking about antibiotic resistance. Today, there is much more interest among both researchers and the general public.”