New antibiotic development hailed as game changing

Abstract

The growing crisis of resistance developing to existing antibiotics and the fact that no new classes of antibiotics have been approved since the 1980s is no secret. In the past 5 years, more and more media reports featuring health leaders and even Prime Ministers and Presidents have warned of a potential antibiotic apocalypse, whereby our existing arsenal of drugs becomes so ineff ective that we will return to a preantibiotic era in which infections once lethal, but currently under control, could kill again. Despite this increasing panic, progress towards actual new antibiotics that can be released on the market has been slow. However, some hope has arrived in the form a new study published on Jan 22, 2015. In this study, scientists from Northeastern University, Massachusetts, USA, detailed a new tech nique for growing potential antimicrobials from soil, the source of most existing antibiotics. The team, working with the pharmaceutical company Novobiotic, Massachusetts, USA, created a multichannel device, called an iChip, that allows soil bacteria to be cultured in their natural environment, leading to production of various promising molecules. The most promising of the 25 or so molecules produced so far is one named teixo bactin, which has strong activity against Grampositive bacteria such as meticillinresistant Staphylococcus aureus and Mycobacterium tuberculosis. “We need to complete preclinical de velopment, which is a further 2 years, involving more animal model and toxicity testing, and also work on issues around production”, says lead researcher Kim Lewis, director of Northeastern University’s Antimicrobial Discovery Center. Teixobactin targets lipids that are key components of the bacterial cell wall, and Lewis describes teixobactin as having evolved to avoid resistance. Unfortunately, this new antibiotic does not show activity against Gramnegative bacteria such as Escherichia coli, limiting its potential usefulness. “This is a good paper showing proof of principle”, says Laura Piddock, Professor of Microbiology and Deputy Director of the Institute of Microbiology and Infection at the University of Birmingham, Birmingham, UK. “Al though teixobactin has no activity for E coli, the approaches taken by Lewis and colleagues can be extrapolated and used by others; this work opens the door on a new era of natural product antimicrobial discovery.” “There are two significant things about this feat”, says Francis Collins, director of the US National Institutes of Health (NIH), Maryland, USA. “The first is that the new antibiotic not only has the ability to kill a wide range of infection-causing bacteria, but to kill them in a way that may greatly reduce the problem of resistance. The second is that researchers identifi ed teixobactin using an ingenious approach that enhances our ability to search one of nature’s richest sources of potential antibiotics—soil. However, over the past few decades, scouring the soil for new antibiotics has proven to be extremely diffi cult because the vast majority of dirtdwelling microbes can’t be grown under traditional microbiological conditions in the laboratory.” Collins also stresses teixobactin’s absence of activity against Gram-negative bacteria, “which include the deadly and rapidly emerging threat of klebsiella and other carbapenem-resistant Enterobacteriaceae”. In the past 3 years, the EU’s Innovative Medicines Initiative (IMI) has announced its “New Drugs 4 Bad Bugs” programme (ND4BB). IMI is Europe’s largest public–private partnership, linking the pharmaceutical industry with leading academic centres, and is gradually establishing networks that will eventually test new antimicrobials. “The IMI antibiotic resistance pro gramme is about much more than clinical development of antibiotics”, says Irene Norstedt, IMI Acting Exec utive Director. “It covers everything from the basic science of antibiotic resistance, including how to get antibiotics into the bacteria in the first place, through the early stages of drug discovery and development, to clinical trials and the creation of a pan-European clinical trial network.” She adds that “it is now clear to most stakeholders in drug development, including industry and academia, that the really big challenges, like antimicrobial resistance, can only be tackled by collaboration between all stakeholders. At the same time, IMI’s successes—including in fi elds beyond infectious disease—amply demonstrate the success and added value of a collaborative approach”. However the IMI programme is not just about finding new ways to tackle antibiotic resistance, but also finding new ways to avoid it. Within the ND4BB programme is the Combating Bacterial Resistance in Europe (COMBACTE) consortium, and one objective of this consortium is to support clinical development of a monoclonal antibody developed by MedImmune, Maryland, USA. This molecule, MEDI4893, targets a toxin produced by S aureus, which is one of the leading bacteria often associated with hospital-associated infections and linked to resistance issues. A For the teixobactin study see Nature 2015; 517: 455–59