Puncturing bacteria key to preventing drug resistance
in favour of antibiotics in their fight against increasingly
drug-resistant 'superbugs'.
Steven Hagens told Chemistry & Industry magazine that, while working at the University of Vienna, he discovered that viruses that infect bacteria and punch holes in their sides could be used to boost the effectiveness of existing antibiotics by up to 50 times.
The overuse of antibiotics since the 1940s has slowly created a host of infections that are resistant to current treatments. Although development of new antibiotics continues, therapies that slow the emergence of resistance are urgently needed.
Although bacteriophage viruses have been tried on their own as a treatment for infection, they have only had limited success because they need to be exactly matched to the bacteria in question.
However, this new technique is different as it doesn't seek to kill the bacteria - merely paralyse it in order to make it easier for the antibiotics to gain access. It is the antibiotics that ultimately kill the bacteria.
During Dr Hagens' research, he administered the antibiotic gentamicin in the presence of bacteriophages to mice. Subsequently, the proportion of mice surviving a lethal dose of Pseudomonas leapt from none to 75 per cent.
"Pseudomonas bacteria for example are particularly multi-resistant to antibiotics because they have efflux pump mechanisms that enable them to throw out antibiotics. A pore in the cell wall would obviously cancel the efflux effect," said Dr Hagens.
This means bacteria become resistant much more slowly because the amount of antibiotic needed to treat an infection is reduced. This is also important because some antibiotics can cause serious side-effects after high-dose treatment. For example, gentamicin has caused deafness.
A second advantage to the technique would be when treating food poisoning because the low levels of antibiotic required would not disrupt the 'friendly' bacteria found in the gut - a big problem with conventional antibiotic treatments. Destroying useful bacteria can cause secondary infections.
Bacteriophages are made from a protein coat containing genetic material. When the phage infects the bacteria, it prevents all host DNA, RNA and proteins from being activated and produced. Instead, phage components are made and these self-assemble into new phage particles. One phage protein produced, a lysozyme, punctures the bacteria wall and releases up to 200 phage 'offspring' through the hole, thus enabling the virus to spread.
"The prospect of using such treatments to prolong the life of existing agents and delay the onset of widespread resistance is to be welcomed," said Jim Spencer, a lecturer in microbial pathogenesis at the University of Bristol.
French pharmaceutical company Novexel are developing NXL104, a beta-lactamase inhibitor that could prevent bacteria becoming resistant to antibiotics such as penicillins, cephalosporins and carbapenems. These drugs are used to treat hospital-based infections caused by gram-negative pathogens.
