Approaches

New ways of fighting bacteria

Four novel approaches to keep killers in check.

I. Faecal transplants

They are not for the squeamish, but faecal transplants are a novel way to tackle bacterial infections. Hospitals are seeing a growing problem of patients with severe diarrhoea caused by Clostridium difficile. This bacterium is often present in low numbers in the gut of healthy people, but when they are treated with broad-spectrum antibiotics the good bacteria die off, allowing C. difficile to take over. Sometimes the only solution is a transplant of faeces from a screened donor, allowing good bacteria to recolonise the gut and outcompete C. difficile.

II. New targets

A common enzyme within many strains of bacteria called the ClpP protease plays a crucial role by cutting up various proteins to carry out important functions within the cell. Researchers led by Stephan Sieber at Technische Universität München have found two sites within the enzyme that prevent it from working, along with a series of compounds that disrupt these two sites.

III. Slime cities

One thinks of bacteria as solitary organisms, unlike larger multicellular creatures, but in fact many human diseases arise when large groups of bacteria start cooperating. In such communities, bacteria secrete substances that form a slimy “biofilm”, which helps them evade our immune system and resist antibiotics. Søren Molin of the Technical University of Denmark is working on molecules that inhibit the growth of biofilms and has shown in particular that they develop in the airways of cystic fibrosis patients with pneumonia.

IV. Breaking the walls

Tuberculosis is a classic example of an infectious disease in which pharmaceutical companies have been reluctant to invest. Being most contagious among people who are malnourished and living in crowded conditions, it is more common in developing countries that cannot afford expensive drugs.

Yet progress is being made through EU funding of the MM4TB research consortium (More Medicines for TB). By screening existing libraries of compounds for anti-TB activity, the team has developed a new class of antibiotics called benzothiazinones, one of which, PBTZ169, is being tested in late-stage animal trials by École Polytechnique Fédérale de Lausanne (EPFL). Promisingly, when the drug is used with existing antibiotics, it seems to work well against multi-drug-resistant strains of TB. The compound works by weakening the bacterium’s cell wall. “The bacteria explode,” explains EPFL’s Stewart Cole.