Wellcome News for Protein Antibiotics
Protein antibiotics are able to kill biofilms such as that shown in the figure for P. aeruginosa. Biofilms are often insensitive to traditional antibiotics (Click to enlarge)
The inexorable rise of antibiotic resistant bacteria threatens to cast our society back to the days before Alexander Fleming's discovery of penicillin. Some of the most problematic of these multidrug resistant microbes are Gram-negative bacteria which, because of their additional outer membrane, are not susceptible to antibiotics that are active against Gram-positive bacteria. The Wellcome Trust has recently funded a collaborative award for the development of a new class of antibiotics, based on proteins that specifically kill Gram-negative bacteria. Spearheaded by Colin Kleanthous in Oxford and Dan Walker in Glasgow, and including colleagues in Oxford, Glasgow, London and the Sanger Institute in Cambridge, the new funding will focus on protein toxins known as bacteriocins. Protein bacteriocins are species-specific antimicrobials that are normally produced by Gram-negative bacteria to kill competitors. The WT-funded consortium will investigate the effectiveness of such protein antibiotics on multidrug resistant Pseudomonas aeruginosa and Klebsiella pneumoniae, which pose huge problems in hospitals around the world. Both organisms cause life-threatening lung and blood infections in infants and immunocompromised patients, and have seen alarming rises in multidrug resistance. Recent estimates from the World Health Organisation suggest that more than 50% of P. aeruginosa isolates-the leading cause of mortality in cystic fibrosis patients-are resistant to the most commonly used antibiotics and alarmingly, often resistant even to the antibiotics of last resort.
"Our consortium brings together a unique mix of skills to investigate the potential of bacteriocins to tackle these major biomedical problems" commented Colin Kleanthous. "We aim discover exactly out how these potent molecules kill their target organisms and at the same time evaluate their effectiveness against different types of infections", added Dan Walker. Traditional antibiotics such as penicillin kill a broad range of bacteria, and this lack of specificity is thought to have contributed to the rise in multidrug resistance in our generation. "The exquisite specificity of protein bacteriocins is a major advantage in this regard" Colin points out. Dan also stresses the importance of the new consortium in training young researchers in protein antibiotic research because "unless we train the next generation of scientists to tackle multidrug resistant bacteria using innovative approaches we'll be drawn back to an era where even minor surgical procedures carries a significant risk of potentially fatal bacterial infections".