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The weird and wonderful hunt for a new antibiotic

2017; Elsevier BV; Volume: 5; Issue: 2 Linguagem: Inglês

10.1016/s2213-2600(17)30017-6

2213-2619

Dara Mohammadi,

Genetics, Bioinformatics, and Biomedical Research

You'd be forgiven for thinking that Adam Roberts is reading out the world's worst Christmas list. “Mouldy peanuts, snail shells, a drain grating clogged with leaves and hair, the boys' urinal in class 7, a manky tea towel, and some moss”, says the microbiologist at University College London (UCL), UK. He's reading out some of the places that members of the public have sent him swabs from, and in doing so is proving that one person's rubbish really can be another's treasure. He set up this citizen science project, Swab and Send, in 2014 as a way to find bacterial compounds that might be made into a new antibiotic, and has been testing each for activity against indicator strains. Against a rising tide of antimicrobial resistance, Roberts says, it is projects such as these that can offer hope for finding new compounds. From thousands of samples in his freezer that showed activity against a weak Micrococcus strain, Roberts has narrowed his selection process down to about 20 samples that also inhibit the growth of Escherichia coli, Meticillin-resistant Staphylococcus aureus (MRSA), and Candida albicans. The path onwards into clinical testing is long and treacherous. Compounds must be proven to be non-toxic to people and, even if money is available, the attrition rate of potential compounds is high. “The biggest hurdle is that you keep finding the same stuff, which isn't great if you're looking for a new compound to circumvent existing resistance”, he says. “If I had unlimited budget I'd go to the most weird and wonderful places on Earth. The best chance of finding the type of compound we need, I think, is by looking where humans have never been.” Expose human pathogens to others that they've evolved with and there's likely to be an existing mechanism of resistance. Expose them to a distant compound that was part of a different evolutionary arms race, though, and like pitting an otherwise undefeatable boxer against a Shaolin monk, you might find a resistance-breaking compound. “If you go down to, say, the bottom of the sea or into caves, the bacteria might have evolved a different chemistry and evolved a different biological warfare”, says Roberts. Scouring the bottom of the ocean is no easy task but there are untapped sources on land. A group at the University of Waterloo in Ontario, Canada, for example, this year analysed soil and water samples from under an aquifer in Colorado, USA. Using terabase-scale metagenomic sequencing, they sifted through 2500 microbes and discovered 47 new phylum-level bacteria groups. Other sources might be (marginally) easier to access. In October last year, Australian researchers showed that a compound in Tasmanian devil milk could kill bacteria such as MRSA. The process of milking these notoriously aggressive animals, though, will require as much a steady hand as it will a steady nerve. Presumably more fond of their fingertips, UK researchers last year found a potential antibiotic compound in a symbiotic bacteria in the nests of leaf-cutter ants. Another group of US researchers have found what they were looking for right under their nose, or to be more specific, inside human noses. Each of these compounds must run the same gauntlet of testing that Roberts will be putting his compounds through. While the hunt continues, says David Livermore, a medical microbiologist at the University of East Anglia in Norwich, UK, the need to protect the drugs that we have is of equal importance. Here, improvements in the treatment of respiratory infections will have an important role. “Pneumonia accounts for more than half of antibiotic use in intensive care units”, he says, adding that they make a substantial contribution to antibiotic prescriptions in primary care, too. “There's therefore a considerable amount of selection pressure for resistance happening in the intensive care setting, and it's where resistance rates are highest.” Present practice with patients suspected of having a pneumonia, says Livermore, is to take a sample and send it to the laboratory for culture and susceptibility testing. In the ensuing 2–3 days until the results come back, the patient is given a broad-spectrum antibiotic. “You may end up having given the patient a drug ineffective against their pathogen”, he says, “or more likely you'll have used a sledgehammer to crack a nut—you'd have given a broad-spectrum drug against a very susceptible bug and done lots of damage to the patient's gut flora”. In 2015, the UK National Institute for Health Research awarded Livermore, along with colleagues at UCL, a £2·5 million grant to tackle this problem. INHALE: Potential of Molecular Diagnostics for Hospital-Acquired and Ventilator-Associated Pneumonia in UK Critical Care, is a 5 year study to assess molecular diagnostics for pneumonia in hospitals. Sampling 1000 patients in intensive care units at four hospitals in the south of England, they will assess the potential of three molecular diagnostic machines to identify important pathogens and their resistance genes within 1–6 h of sampling. In this first phase, which is underway, the aim is to see if the machines give the same results as standard methods. The best performing machine will then be carried through to a clinical trial in which half of patients will be given treatment based on its rapid, molecular findings, and half will be managed in the normal way. Livermore estimates that they are 18 months off from starting the clinical trial. In the meantime, at the top of everybody's list of wants will be new antibiotics.