By Katharina Richter, University of Adelaide
Scientists are exploring new strategies to win the war against superbugs.
Invisible to the naked eye, bacteria are constantly evolving in their quest for survival.
Over the years, the misuse and overuse of antibiotics have inadvertently fuelled the rise of antibiotic-resistant bacteria, also known as ‘superbugs’.
These superbugs are equipped with ingenious defence mechanisms, like forming castles of slime called biofilms, in which bacterial communities are well protected against attacks from antibiotics and the immune system.
In 2019, globally 1.27 million people died from antibiotic-resistant infections.
However, scientists are not backing down. They are arming themselves with cutting-edge treatment strategies and harnessing the power of artificial intelligence to combat this growing threat.
And there is global recognition of the importance of this work. In August 2023, G20 health ministers, meeting ahead of the main leaders’ summit in September, committed to a comprehensive strategy to continue the fight against antimicrobial resistance.
Imagine antibiotics as soldiers fighting bacteria on the battlefield.
Doctors once used antibiotics like precision-guided missiles, selectively targeting specific infections. However, over time, a different scenario unfolded. Antibiotics were overused in medicine, prescribed for minor illnesses where they were ineffective, like launching missiles at harmless decoys. Prematurely ending antibiotic courses allowed resilient bacteria to survive, carrying battle lessons back to their ranks.
Additionally, agriculture and livestock used enormous amounts of antibiotics at low doses to promote livestock growth and prevent disease, thereby flooding the environment with antibiotics and arming the enemy with our own weapons.
These missteps enabled bacteria to adapt and develop resistance over time. The bacteria who managed to survive the antibiotic attack, passed on their resistance to their descendants.
This process has led to the emergence of superbugs that can resist multiple antibiotics, rendering once-effective treatments useless.
Adding to this challenge is the formation of biofilms.
By default, bacteria like to stick together and build walls of slime around them. Within this ‘slime castle‘, bacteria are extremely well protected against any enemy.
The close neighbourhood of bacteria enables them to ‘chat’ to each other, streamline defences and exchange information on how to become resistant to antibiotics.
Biofilms are involved in 80 percent of infections in the human body — such as surgical site infections, non-healing wounds and implant infections — that are extremely difficult to treat.
The scientific community recognises the urgent need for new approaches to tackle antibiotic resistance and biofilms, particularly as no new classes of antibiotics have been discovered since the 1980s.
Researchers are exploring various strategies, some of which hold promising potential:
Bacteriophages, or phages, are viruses that infect and kill specific bacteria. They can be engineered to target antibiotic-resistant bacteria without harming beneficial ones. Scientists are creating effective ‘phage cocktails‘ that can tackle a range of bacterial infections.
The human immune system produces molecules known as antimicrobial peptides and antibodies to fight infections. Researchers are exploring the potential of these natural defenders as therapies. Antimicrobial peptides can directly target bacteria, while antibodies can tag bacteria for destruction by immune cells, enhancing the body’s ability to clear infections.
Cold plasma, a state of matter containing energetic ions, free electrons, and reactive particles, is being investigated for its antimicrobial properties. Cold plasma can inactivate bacteria by damaging their outer membranes, disrupting their cellular processes. This emerging field, known as ‘cold plasma medicine’, could offer an antibiotic-free and non-invasive approach to treating infections.
Researchers are investigating strategies, such as small molecules (which are small enough to move through the biofilm slime and reach the bacteria inside), nanomedicine or oxygen therapy, that can weaken bacterial defences, making them vulnerable to antibiotics again. By disrupting the bacteria’s ability to resist antibiotics, enhancers could give a second life to existing treatments.
Bacteria communicate through chemical signals in a process called quorum sensing. This communication allows bacteria to coordinate their actions, including the formation of biofilms. Quorum sensing inhibitors are designed to disrupt this communication, preventing biofilm formation and making bacteria more susceptible to antibiotics and the immune system.
These agents target the structural integrity of biofilms, breaking them apart and exposing the bacteria within to antibiotics. By dismantling the protective slime walls of biofilms, disruptors, such as enzymes, nitric oxide therapy, essential oils, or gallium-based medicine (which looks like food to bacteria, but is actually toxic to them), allow antibiotics to reach and eliminate bacterial colonies more effectively.
Known for its gene-editing capabilities, CRISPR-Cas technology could be used to target and disable antibiotic resistance genes within bacteria, potentially restoring their susceptibility to antibiotics.
While these innovative strategies show promise, their development and optimisation require substantial research and experimentation. This is where artificial intelligence steps in.
AI algorithms can analyse vast databases of molecular information to identify potential compounds with antibacterial properties.
By simulating interactions between drugs and bacteria, AI accelerates the drug discovery process, helping scientists uncover novel treatment options more efficiently.
Additionally, AI-driven models can simulate the behaviour of biofilms and bacterial colonies, aiding researchers in designing strategies to disrupt these communities effectively.
This computational approach provides valuable insights that guide the development of treatments that can prevent persistent infections.
The race against superbugs is a race against time.
The collaborative efforts of researchers worldwide, combined with innovative treatment strategies and AI-powered insights, provide hope for a brighter future.
While science is delivering potential new treatments, responsible antibiotic use is a key part of ensuring existing treatments remain effective.
That means doctors and their patients have a role to play in ensuring only the necessary use of antibiotics, while the agricultural and food sectors also need to limit antibiotic use in livestock.
Research funding is critical, so policymakers too have a critical part in the fight.
Dr Katharina Richter is a biomedical researcher and science communicator at the University of Adelaide. Her research focuses on developing effective treatments against antibiotic-resistant bacteria and translating them from the lab to real-life applications, and improving the health literacy of society through effective science communication.
Dr Richter’s research has been funded by the University of Adelaide, the National Health and Medical Research Council, the Medical Research Future Fund, The Hospital Research Foundation Group, and the European Society of Clinical Microbiology and Infectious Diseases.