Silent guardians: How unstudied bacteria could hold the key to AMR solutions

Mahmoud Naser Aldine, MSC

3/17/2025 Facebook Twitter LinkedIn Email

By definition, antimicrobial resistance is the ability of microorganisms like bacteria to evolve and develop strategies to protect themselves from antimicrobial agents. AMR is one of the most critical challenges of our time: The repertoire of antibiotics is shrinking, and the number of people dying because of AMR is on the rise. Every year, around 1.27 million people die directly because of AMR, and 4.5 million deaths are attributed to bacterial resistance, which is more than the total death toll from HIV, malaria and tuberculosis combined. (1,2) Yet, there are no immediate solutions.

Development of new antibiotics is expensive, slow and fraught with high failure rates. This has resulted in the stagnation of the pharmaceutical pipeline for new antibiotics. Making matters worse, most pharmaceutical companies tend to prioritize more profitable treatments over new antibiotic development. This creates a vicious cycle, forcing health care providers to rely only on current antibiotics, which in turn fuels AMR.

But a solution may be hiding in plain sight — the unlimited diversity of undiscovered bacteria that is waiting for us to study. Scientists have reported that only 1% of the microbial world has been studied, leaving the vast majority unexplored. (3,4) These silent guardians potentially could hold the key to solving the AMR problem by providing an unlimited reservoir for novel antimicrobial peptides that we’ve never encountered before.

What makes unstudied bacteria so promising?

Although unstudied bacteria are challenging to study as they are difficult to culture in lab conditions, they are one of the most promising natural reservoirs for unique novel antimicrobials. These bacteria are known to thrive in extreme environments like hot acidic springs, deep ocean floors, deserts or under glaciers. (5) Such environments make them evolve unique biochemical pathways to survive these conditions.

One outcome of these adaptions is the synthesis of novel antimicrobial compounds with unique modes of action. (6) Therefore, these microorganisms could provide us with new compounds that can bypass AMR. The proven track record of existing antibiotics derived from microbes like Streptomyces, which has provided us with over two-thirds of known antibiotics, underscores the promise of unstudied bacteria.

Discovering novel antimicrobial peptides challenges and solutions

AMPs are small peptides produced by bacteria to kill or inhibit the growth of other bacteria. They can target different parts of the pathogens, but mostly their cell membrane, resulting in cell lysis. Advancements in technology can enhance the discovery of novel AMPs through:

• Genomics and metagenomics: Sequencing of environmental samples without the need for culturing, allowing the discovery of novel AMP biosynthetic gene clusters.
• Synthetic biology: Replication and cloning of AMP BGCs in model lab-friendly microorganisms like coli and B. subtilis.
• Artificial intelligence tools: Development of algorithms that can enhance the detection of novel AMP BGCs and predict which ones hold potential strong antimicrobial activity.
• Isolation chip technology: Allowing researchers to grow unculturable bacteria in their natural environment, enabling us to study their properties.
• Collaborative work: Addressing the cost challenges of antibiotic research requires global collaboration and partnerships between academic institutions, biotech companies and the pharmaceutical industry.
• Policy: Global organizations and governmental institutions should enforce stricter policies regulating antibiotic use and invest more in antibiotic research.

Conclusion

AMR is a silent pandemic posing an immense threat to the public globally, demanding immediate action. However, nature’s silent guardians are ready to step up and help in the fight against AMR by serving as a natural reserve for novel antimicrobials. However, harvesting these novel compounds requires embracing the latest technologies, encouraging collaborations and bridging the gap between academia, industry and global organizations. If these efforts are successful, we may be able to uncover the next generation of novel antimicrobials to tackle this looming crisis.

Stay tuned for a future post from Naser Aldine, where he will share an example from his research showing how unstudied bacteria may be key in the fight against AMR.

Photo: Bacillus subtilis, a bacterium known for producing various antimicrobial compounds

References  

1. Antimicrobial resistance. World Health Organization Fact Sheet. 
2. Murray, C.J. et al. Global Burden of Bacterial Antimicrobial Resistance in 2019: A Systematic Analysis. The Lancet. 2022;399:629–655.
3. There Can Be 1 Trillion Species on the Planet. Science-Atlas.com. 
4. Locey, K.J. & Lennon, J. T. Scaling Laws Predict Global Microbial Diversity. Proc Natl Acad Sci U S A. 2016;113:5970–5975.
5. Lodhi, A.F., Zhang, Y., Adil, M. & Deng, Y. Antibiotic Discovery: Combining Isolation Chip (iChip) Technology and Co-Culture Technique. Appl Microbiol Biotechnol. 2018;102:7333–7341.
6. Wang, X., Deng, Z. & Gao, J. Exploring the Antibiotic Potential of Cultured ‘Unculturable’ Bacteria. Trends Microbiol. 2024;32:124–127.