The global battle against a miniature but lethal adversary: antibiotic-resistant bacteria

11 April 2017

A war is raging.

Since the 1940s scientists have been fighting to protect us from bacterial strains that continue to evolve. The bacteria are developing resistance to antibiotics, our weapons against them, forcing us to find new ways to protect ourselves. The development of antibiotics has not kept up with the rate that resistance is developing. Some bacterial strains have become so advanced that we have no way to fight them. They’re called superbugs, and they’re taking lives.

Video: Global Quest to Beat Superbugs

In January 2017 a Nevada woman died from a superbug that was immune to 26 different antibiotics. The bacteria developed resistance to a class of antibiotics that are considered our last line of defense, currently used when all other treatments fail.

Luckily, the antibiotic-resistant strains of bacteria that we are aware of are not yet easily transmitted, but if a highly contagious strain were to develop resistance, there would be a frightening epidemic.

Researchers at the Institute of Molecular Bioscience (IMB) Associate Professor Lachlan Coin and Dr Mark Blaskovich, along with their colleagues, have joined the global fight against superbugs.

“This is very real. An epidemic could happen anytime. If rapidly spread strains of bacteria were to become resistant to antibiotics, we would be plunged back into a pre-antibiotic era where anything that compromised our immune system would be off-limits,” said Associate Professor Coin.

“Surgery and cancer therapies, for example, would no longer be possible. Those at most risk would be young children and the elderly.”

A report commissioned by Public Health UK ‘tackling drug-resistant infections globally' states that there are currently 700,000 deaths per year worldwide from drug-resistant infections. The report estimates that without policies to stop the spread of antimicrobial resistance, deaths could increase to 10 million per year.

Recommendations in the report include funding research into new antibiotics and new diagnostics. IMB research teams have secured funding to do just that. They are tackling the problem in three ways:

  1. Developing a rapid test that allows clinicians to distinguish bacterial from viral infections, to reduce the incidence of unnecessary prescription of antibiotics.
  2. Rediscovering antibiotics that were discovered in the past but not developed into drugs.
  3. Creating the world’s largest database for antimicrobial activity by testing compounds from across the globe to uncover molecules active against bacteria.

Creating a new diagnostic tool

“A huge part of the problem is the overuse and misuse of antibiotics, with 50% prescribed unnecessarily,” said Professor Coin.

Inappropriate uses of antibiotics, to treat colds and flus caused by viruses, for example, help bacteria to develop drug resistance. There are subtle differences between the symptoms of bacterial and viral infections. Identifying that a bacterial infection exists, and correctly characterizing what type of bacteria is causing it, are imperative to prescribing the correct antibiotic to target it. But, the current testing process is long and ineffective, taking 24-48 hours. Patients are therefore often initially given a broad-spectrum antibiotic that is ‘hit and miss.' 

“We have found the biomarkers that indicate a bacterial infection and developed a tool that will allow clinicians to test for those markers at the point of diagnosis within one hospital shift – 6 hours,” said Associate Professor Coin.

The technology is housed in a little portable sequencer the size of a mobile phone. The research teams are collaborating with clinicians at the Royal Brisbane and Women's Hospital to ensure the technology applies to the clinical setting.

They are also tapping into internationally collected data on bacterial resistance to inform treatments.

“Once clinicians know the DNA sequence, they can check it against a database to see what that particular bacteria is resistant to and prescribe accordingly.”

The research team is currently testing the method against existing tests to confirm its accuracy. The next step is improving the technology to make it more affordable followed by clinical trials.

The development of a point-of-care diagnostic test is considered so important to global healthcare that a £10million prize, The Longitude Prize, has been set as a reward for its discovery. Similarly, President Obama set a $US20million prize.

Uncovering new antibiotics from old discoveries

In the 1950’s and 60’s antibiotic exploration was at its peak and many antibiotics were discovered. With so many choices, only some were developed. Dr Mark Blaskovich and his team are looking for diamonds in the rough.

“We have ‘rediscovered’ a class of antibiotics, the octapeptins, similar to the current antibiotic of last resort, colistin,” said Dr Blaskovich.  

“Resistance to the colistin antibiotic of last resort happens very quickly, partly because it can cause kidney damage, so can’t be used at higher doses. Octapeptins are still effective against bacteria that have developed resistance to colistin. They also seem to cause less damage to the kidney. So this is an important discovery that could save lives.”

The research team has made 300 different synthetic versions of the antibiotic and is currently making modifications to improve its activity, reduce toxicity, and improve absorption into the body, to make an effective drug.

The world’s largest database for antimicrobial activity

To help create new antibiotics researchers at IMB set up a screening program to test compounds from chemists across the globe for free. They’re searching for molecules that are active against bacteria.

“We are facing a potential catastrophe of untreatable bacterial infections. New antibiotics are desperately needed,” said Dr Blaskovich. 

The program has been running for two years and has now tested over 140,000 compounds from 35 different countries. It allows chemists who may never have thought their compounds could be antibiotics to see if they are active. The results are eventually made publicly available so that all researchers in the fight against superbugs can work with the data. Importantly, the chemist sending the compound retains all rights to the compounds and the data.

The Wellcome Trust, a biomedical research charity based in London, and the University of Queensland funded the program, which is called CO-ADD – the Community for Open Antimicrobial Drug Discovery.

“This is a problem of global significance, it will take a global effort to solve it, and we are against the clock. We don’t want to duplicate efforts, where different groups make the same compounds because they don’t know someone else already tried,” said Dr Blaskovich. 

“This database helps direct research efforts by highlighting the things that have been found ineffective, and leading study towards compound structures that show promise.”

The compounds that CO-ADD identifies as possible antibiotics can then be submitted to programs like IMI Enable or Carb-X, which take promising compounds to develop them into new antibiotics.

"We're helping chemists around the world to package their data so they can apply to programs like IMI Enable and Carb-X, to hopefully speed up the rate of discovery."

Superbugs pose an imminent threat. A UN General Assembly held on September 21, 2016, brought world leaders together to commit to addressing antimicrobial resistance. It was only the fourth time that a health issue has been taken up by the UN General Assembly – placing antimicrobial resistance alongside HIV, noncommunicable diseases, and Ebola. Researchers at the Institute of Molecular Bioscience are leading the charge in Australia.

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