Can biochemistry help to prevent antibiotic resistance?

Antibiotic resistance is one of the key global health challenges of our time. Though resistance to drugs can occur naturally, the misuse of antibiotics is exacerbating the issue — leading to longer hospital stays, higher healthcare costs and increased mortality. With scientists scrambling for solutions, biochemistry may be a panacea to the problem.

The problem: the scale of antibiotic resistance

Antibiotic Research UK call it a “global catastrophe”. The UK Health Secretary, Matt Hancock, has called for an “urgent global response”. Former Chief Medical Officer for England, Sally Davies, says that “the world is facing an antibiotic apocalypse.”

Antibiotic resistance (also known as antimicrobial resistance) is one of the defining public health concerns of the 21st century. Through the overprescription and misuse of antimicrobial drugs, microbes are able to resist the effects of medication that once successfully treated them. When microbes become multidrug-resistant (MDR), superbugs emerge.

The issue is rooted in both structural inefficiencies within healthcare systems as well as patient behaviour. In the UK, the NHS estimates that as many as 1 in 5 antibiotics may be prescribed inappropriately, with patients being given the drug for minor ailments such as sore throat, cough and sinusitis. To compound the problem, there is a medication adherence problem: in the US, up to 50% of people do not take their medication as prescribed.

Despite the rollout of preventative measures such as only using antibiotics when necessary, deaths from antibiotic resistance are already at an all-time high.

In the United States alone, antibiotic-resistant bacteria and fungi cause 2.8 million infections and 35,000 deaths each year. Every 11 seconds someone is infected. Every 15 minutes someone dies . If epidemiological trends continue unchecked, the problem is poised to cause 50 global million deaths a year by 2050 and an economic productivity loss of around $100 trillion

If the tide is not stemmed, researchers predict that a worldwide pandemic akin to the cataclysmic Spanish Flu outbreak of 1919 (which killed between 30 and 50 million people or roughly 4% of the Earth’s population at the time) could also be imminent. Wholesale preventative action is urgent.

The science: how do bacteria become resistant to antibiotics?

Antimicrobials treat infections caused by harmful microbes, of which there are two kinds: bacteria and fungi. While most microbes are harmless and even beneficial to humans, harmful microbes called germs can cause infections and disease. Antibiotics are used to kill or inhibit the growth of bacterial infections while antifungals are administered to treat fungal infections.

Bacteria develop resistance to antibiotics when they genetically mutate or change in a way that reduces or eliminates the effectiveness of drugs designed to cure or prevent infections. When these bacteria are able to multiply and spread their drug-resistance to other bacteria, the harm they do amplifies significantly. By developing the ability to neutralise an antibiotic drug before it can take effect, other bacteria can pump the antibiotic out and render it useless in fighting infection.

Once a multidrug-resistant pathogen such as Pseudomonas aeruginosa takes hold, it is able to rapidly spread between hosts — crossing international borders and contributing to a global health crisis.

The potential solution: biochemistry enters the fray

Biochemistry is a field of medical science that combines the core tenets of biology and chemistry. In simple terms, it is the study of living matter. 

The largely laboratory-based field is crucial for studying how antibiotics destroy bacteria by targeting their biological processes. Thanks to breakthroughs in biochemistry, we now know how antibiotics work. We even know the molecular structure of antibiotics such as penicillin and streptomycin.

Biochemistry also permits us to observe the pathways and mechanisms that cause physiological drug-resistance. Antibiotic or antimicrobial resistance has a biochemical basis. Through an ongoing understanding of these processes, scientists can design and synthesise new and effective antimicrobial compounds in a bid to combat the persistence of drug-resistant infections.

The Streptomyces bacteria genus, for example, naturally produces antimicrobial substances — supplying about two-thirds of all clinically useful antibiotic drugs. Armed with knowledge on how this bacterium’s metabolic pathways generate natural antibiotics, scientists are beginning to manipulate these pathways to produce new antibacterials.

Biochemists are coming up with innovative strategies to combat antimicrobial resistance. One novel approach involves combining an FDA-approved non-antibiotic drug with a specific antibiotic. According to researchers at Monash University in Australia, this unorthodox combination can boost the effectiveness of antibiotics against gram-negative 'superbugs'. The combination enables it to breach the outer membrane barrier of resistant bacteria and restore the activity of an antibiotic. 

In 2015, the first transferable resistance to polymyxins, a type of antibiotic, was discovered. This was alarming because polymyxins have long been used as a last line of defence against serious infections caused by superbugs such as Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii (A. baumannii). 

Since then, researchers have been testing different combinations of drugs or compounds with polymyxins to try and improve their effectiveness against these superbugs — and with some success. 

When combined with polymyxin B, the new cystic fibrosis drugs, ivacaftor and lumacaftor, were found to increase antibiotic activity. So too was closantel, a drug used to treat parasitic worm infections.

Another innovative method involves using metals and metalloids as an alternative treatment for infections. At the University of Connecticut (UConn), a research team led by Kumar Venkitanarayanan applied selenium (Se) to A. baumannii, which is one of the most antibiotic-resistant bacteria. Selenium is a metalloid that’s recognised as a dietary oxidant and an essential micronutrient that helps the immune system function. After applying it to A. baumannii, the nanosized selenium was found to inhibit pathogen growth.

The fight against antibiotic resistance is not just limited to the laboratory. Success requires collaboration across different areas of science. According to the University of Queensland’s Dr Mark Blaskovich:

"In the short term, the greatest potential for reducing further development of antimicrobial resistance lies in developing a rapid test that can quickly tell whether or not you have a bacterial infection (as opposed to a viral cold or flu), and whether you really need an antibiotic."

Blaskovich argues that the best immediate course of action is to identify whether a patient already has a drug-resistant infection prior to being prescribed an antibiotic.

This might become a reality sooner rather than later. With more reliable diagnostics and data sharing across the medical world, the bacterial genetic tests Blaskovich is describing can now deliver sample results in hours rather than days. The result? Faster detection of antibiotic-resistant pathogens and more accurate predictions of a pathogen’s resistance to a particular antibiotic. This, in turn, can directly help reduce the overprescription and misuse of antibiotics.

For more insights into the ever-changing world of the life sciences sector, stay tuned to the SRG blog.