Promising Treatments Against Resistant Bacteria: Research on New Antibiotics and Alternatives for Microbial Infections

[This article has been written by Sara M. Soto, Associate Research Professor and Head of the Viral and Bacterial Infections Programme at ISGlobal, Clara Ballesté-Delpierre, Associated Research Professor and Coordinator of the Antibiotic Resistance Inititative, Jemima Chantal D’Arcy, Vaccinologist and Science Communicator on an internship in ISGlobal's Outreach Department, and Marina Tarrús, Outreach Technician at ISGlobal.]

Ever since antiquity, humans have used substances with antibacterial properties, such as the mummification balms used in ancient Egypt. The “conscious” discovery of antibiotics, however, dates back to 1928, when Alexander Fleming discovered penicillin. The British physician and scientist chanced upon a fungus, Penicillium notatum, that was capable of preventing the growth of Staphylococcus aureus bacteria. After observing the phenomenon, Fleming eventually determined that penicillin was the substance responsible for this bactericidal effect—a finding that marked the dawn of modern medicine.

Due to problems associated with the purification of the active ingredient, the first doses of penicillin were not administered as antibiotic treatment until the Second World War, when the drug saved thousands of wounded soldiers from death by infection.

On receiving the Nobel Prize in Medicine in 1945, Fleming himself warned that the imprudent use of the drug could lead to the emergence of penicillin-resistant bacteria

Penicillin proved effective and the world rejoiced. However, in 1943, just twenty years after Fleming’s discovery, the first bacteria capable of evading the drug’s effect appeared on the scene. Like all antibiotic resistance, this was a natural phenomenon that arose sporadically: bacteria occasionally evolve in such a way that they manage to escape an environment that is harmful to their growth. On receiving the Nobel Prize in Medicine in 1945, Fleming himself warned that the imprudent use of the drug could lead to the emergence of penicillin-resistant bacteria.

Fleming’s warning proved prescient. As new antibiotics have emerged, bacteria have developed resistance to these drugs. In the early days of antibiotics, half a century ago, resistance tended to emerge after a drug had been in use for a decade. Since the 1980s and 1990s, when antibiotics started to be widely used outside of hospital settings, this process has accelerated, shortening each new drug’s window of effectiveness. Consequently, developing new generations of antibiotics and researching new treatments have become pressing matters in recent years.

The Next Pandemic Will Be Silent

This exponential decrease in the effectiveness of antibiotics is linked to our model of consumption, wherein self-medication, lack of responsibility and widespread abuse of antibiotics—both in humans and in agriculture and animal husbandry—are commonplace. The effects are serious for our society, as well as for animal health and the ecosystem we inhabit, as reflected by the One Health concept. Consider this fact: in 2019, 1.27 million people died worldwide as a result of antimicrobial resistance. By 2050, this figure is expected to rise to 10 million people per year, surpassing the lethality of cancer.

The situation is so alarming that, in 2019, the WHO declared antimicrobial resistance to be one of the top ten threats to global health. It is called the ‘silent pandemic’ because of the lack of international awareness regarding this issue

The situation is so alarming that, in 2019, the World Health Organisation (WHO) declared antimicrobial resistance to be one of the top ten threats to global health. It is called the “silent pandemic” because of the lack of international awareness regarding this issue.

New Tools: What Are We Researching?

To counter the threat to the planet posed by this pandemic, researchers have been exploring several avenues in the hopes of discovering and developing new antimicrobial therapies. Again, as with penicillin, the time, effort and obstacles that a new molecule must overcome between the initial discovery and commercial availability make for a winding, tedious journey that often leads to failure. If we also consider the modest return on investment associated with developing a new antibiotic, we can understand why many pharmaceutical companies abandon this line of research in order to focus on more lucrative ventures.

There is still time to prevent a pandemic that could soon leave us without effective treatments for infections currently seen as simple

The WHO has published a list of 12 priority superbugs that are resistant to multiple antibiotics are therefore urgently require the development of alternative antimicrobial treatments. To address this situation, public research groups are the main drivers of the development of new tools via spinoffs and startups, as well as through the licensing of “mature” products to the pharmaceutical industry. The new tools and strategies they are currently exploring, with varying degrees of success, include the following:

1. Bacteriophages. The advantage of phagotherapy is that phages—viruses that infect bacteria—are specific to a target bacterial population, have low toxicity and can be administered by different routes. Disadvantages include the fact that phagotherapy requires knowledge of the target bacteria, resistance can develop more easily and the regulatory pathway remains unclear, casting doubt on the cost-effectiveness of this approach for companies.
2. Vaccines. Several vaccines are currently under development to target pathogens associated with antimicrobial resistance in the preclinical and clinical stages. Vaccines against M. tuberculosis and C. difficile are in the advanced stages of development (phase III), but their fate remains uncertain.
3. Antibody therapy. Monoclonal antibodies (mAb) have to be specifically designed against individual bacteria, and the clinical development of each mAb must be done separately. The main advantages of mAb are the optimal selection of the antibody target and high specificity, which makes for fewer side effects and less selective pressure for cross-resistance.
4. Microbiota. The human microbiota has a major impact on the health and immune response of the host. Bacteria living in our intestinal tract can be stimulated to prevent and cure superbug infections, but these treatments are still experimental.
5. In addition to all these alternatives, efforts are being made to research and develop new antibacterial molecules of both natural and synthetic origin. One natural source that offers many opportunities to find such molecules is the ocean. At ISGlobal, we have studied microalgae (NoMorFilm project) and have found, among other things, fatty acids and chlorinated compounds with potent antimicrobial activity. ISGlobal’s new antibacterial research group is also developing gold (III) complexes and peptides as possible new therapies to combat multidrug-resistant bacteria.

ISGlobal’s new antibacterial research group is also developing gold (III) complexes and peptides as possible new therapies to combat multidrug-resistant bacteria

If we combine these research efforts with greater awareness among health professionals and society regarding the use of antibiotics, there is still time to prevent a pandemic that could soon leave us without effective treatments for infections currently seen as simple, thereby endangering modern medicine as we know it today.