Norwich leading the fight against antibiotic resistance

It’s mid-November, it’s cold, it’s dark and as I make my way to the Conference Centre I see a crowd of people gathered inside. They are here for the Friends of the John Innes Centre’s Fight Against Antibiotic Resistance event – an evening of talks by Norwich Research Park scientists. It’s busy, and some 250 people – a mix of students and members of the public – have turned up to hear what the night’s speakers have to say.

Setting the stage for the evening is the John Innes Centre’s Mervyn Bibb. As the audience settles in, he begins to explain the current crisis of antibiotic resistance and problems associated with discovering new drugs to treat resistant pathogens.

Very few new antibiotics have been discovered since the so-called golden age of the 1950s and 60s, and the current pool of available antibiotics has been poorly stewarded. In many countries, antibiotics can be readily bought without a prescription. Even where prescriptions are required for antibiotics, there is an apparent cultural trend to overprescribe them. The use of antibiotics for nonmedicinal purposes further complicates matters. Around 30% of antibiotics produced in the US, for example, are used for promoting growth in livestock.

The frequent exposure of bacterial populations, coupled with their incredible ability to develop drug resistance through multiple pathways, has resulted in a rapid increase in the number of multi-drug-resistant (MDR) organisms. Methicillin-resistant Staphylococcus aureus (MRSA), perhaps the most well-known MDR pathogen, is sadly just one member of an ever-growing list.

To make matters worse, the pharmaceutical industry has almost completely lost interest in developing new antibacterial compounds due to their low market value and short term usage. In Europe, around 25,000 people die each year from antibiotic-resistant infections and members of both houses of parliament have stressed the dangers of leaving this problem unchecked.

Thankfully, there are researchers trying to solve the problem. Tonight we get to hear from three of them.

Leafcutter ants harness the antibacterial power of bacteria

First up is Matt Hutchings, a molecular microbiologist at the University of East Anglia. He explains that the majority of antibiotics (and an even greater proportion of anticancer agents) are derived from soil bacteria. Work on finding new compounds from these bacteria has fallen in to decline in the past few decades as searches yielded the same compounds time and time again.

However, recent advances in DNA sequencing have revealed a massive amount of hidden diversity in these bacteria – locked away in cryptic gene clusters, not active under laboratory conditions. With the power of whole genome sequencing comes the opportunity to discover these hidden pathways and rapidly increase the number of potential drugs while, at the same time beginning to uncover how these organisms synthesise such compounds.

These microorganisms can also be harvested from new environments. Hutchings’ flagship example is the leafcutter ant. These ants actively cultivate impressive fungal gardens for food, effectively predating human agriculture by 50 million years! Perhaps equally incredible, is that the ants harness the antibacterial power of the bacteria that live on their bodies. These microbes protect the fungus and, in turn, the ants’ livelihood from harmful pathogens that would otherwise thrive. Hutchings believes that screening these ant colonies is a shortcut to finding novel antibacterials, as these microbes have essentially been hand-picked for this purpose.

The door to the era of personalised medicine has been opened

Next is Justin O’Grady, brandishing what is, although reminiscent of an oversized USB stick, a miniaturised DNA sequencer. Over the past ten years, the price of genome sequencing has dropped dramatically. The affordability of such technology has opened the door to the era of personalised medicine and molecular diagnostics, whereby pathogenic organisms can be identified quickly and accurately from their genetic code.

This technology has important implications in sepsis cases, where an hour or two either way can determine patient survival. Were such diagnostics available, clinicians could quickly identify the target organism. More accurate treatment would mean that non-pathogenic bacteria would not be targeted, ultimately slowing the development of MDR. O’Grady has developed this diagnostic pipeline considerably and, although he admits that it is currently a proof of concept, he appears confident that this technology will become much more widely available as it becomes cheaper and more powerful.

A probiotic to help balance vital gut biota

Last to speak is Lindsay Hall, presenting work on the importance of healthy microbial communities in the gut. Humans are dependent on their microbiota – the average adult it is estimated to have ten times as many bacterial cells as human cells. These microbes are vital to human health – they are critical to immune development and provide around 20% of our daily energy intake through the digestion of carbohydrates we ourselves can’t process.

In premature babies, heathy microbial communities are not present – a problem amplified by the need for high doses of antibiotics in babies born by Caesarean section. This microbial dysbiosis is a key factor in the development of several diseases, including the devastating necrotising enterocolitis – the potentially fatal inflammation or perforation of the intestine. To combat this, Hall’s group has developed a probiotic to help restore balance to the disrupted gut biota. Early clinical trials have already demonstrated reduced mortality rates in babies treated with the probiotic. Hall wants to observe the development of the gut flora through longitudinal study of stool samples from healthy and premature babies. Probiotics may present a powerful complimentary approach to antibiotic treatment and may create a useful avenue for combatting traditionally difficult diseases.

The broad range of expertise on display and the level of engagement between the speakers and the audience was truly impressive. The communication of science is a two-way street – it is not only about education, but also understanding the public perception of academic research. If we are to tackle important problems, such as the one we face with antibiotic resistance, it is vital that this link be maintained. An important role of scientific researchers is to help inform public opinion and events like these are an excellent starting point, but I begin to wonder if traditional views can be shifted so easily.

During his introduction, Mervyn Bibb asked the audience to consider two questions: firstly, do they think antibiotics are currently too cheap; and secondly would they be willing to pay more for them. The audience seems to agree with the first statement, but their response to the second is much more ambiguous.

Thom is a first year PhD student at the John Innes Centre. You can find out more about Friends of John Innes Centre events here.

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