The Discovery of New Antibiotics

In 2019, 1.27 million people died due to infections untreatable by current medications.

Researchers from MIT and McMaster University have employed a machine learning algorithm to identify an antimicrobial compound which effectively kills Acinetobacter baumannii bacteria that have become common hospital pathogens due to antibiotic resistance. Their findings are published in Nature Chemical Biology journal.


As recently as last year, there have been few new antibiotic classes released onto the market. These so-called “first-generation” antibiotics target Gram-positive bacteria responsible for pneumonia, wound infections, urinary tract infections and bloodstream infections; yet their lack has resulted in increasing resistance against existing treatments that is an alarming threat to public health.

Antibiotics were once seen as the cornerstone of medicine, but their discovery in the late 19th and early 20th centuries heralded an age of hope for healthcare, but that time is drawing to a close as resistance increases against these drugs, making treatment harder and more costly – according to estimates, new infections caused by resistant bacteria will increase by 2050 as current trends persist.

Lack of innovation in antibiotic discovery has been identified as a cause for this decline; according to one report, only 1 of 15 antibiotics currently in preclinical development will make it to patients due to high costs associated with developing such medicines and poor returns from investments due to declining demand.

Scientists have long searched for novel antibacterial compounds. Soil-dwelling bacteria such as Actinomycetes and Streptomyces have proved invaluable as sources of antibiotics; cultivating and screening them for antibiotic activity makes this approach highly successful, producing some of the most potency antibiotics like penicillin and salvarsan.

Scientists are exploring innovative methods of discovery. For instance, researchers from McMaster University and Massachusetts Institute of Technology used artificial intelligence to find APC-3958 — an antimicrobial drug capable of killing Acinetobacter baumannii — which was then found by searching a database containing chemicals known to interact with its quorum sensing system.

Discovery of antibiotics is a complex endeavor; any drug must be safe for human use while still effective against resistant bacteria. Distribution challenges must also be considered; those in need must have access to them. Therefore, novel economic models designed to distribute risks and profits of antibiotic discovery among different stakeholders have become necessary solutions.


Discovery of antibiotics has not been an easy journey; even scientific discoveries that look promising don’t guarantee they’ll reach clinical use. On average, new drugs take about 10 years from their development in a laboratory to hospital use where they undergo numerous trials to ensure safety and efficacy. A lack of investment, high risk involved with creating antibiotics (typically prescribed only to treat life-threatening infections), as well as pressure from doctors and patients to use existing medicines sparingly are among some factors holding back progress on new antibiotics development.

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Faced with this daunting challenge, many large pharmaceutical companies have abandoned their antibiotic search, leaving smaller and nimbler firms to pick up the task. This approach has resulted in exciting new antibiotics – for instance one which targets drug-resistant versions of Acinetobacter baumannii through targeting their toxin production – as well as tailored antibiotics tailored specifically for individual pathogens.

New generations of antibiotics will require a distinct business model. High-volume sales that might soon become ineffective due to resistance development cannot be relied upon as the sole means of covering development costs and making money for pharmaceutical companies; so other strategies must be employed in order to recoup development expenses and make profits for pharmaceutical firms. One method would be delinking sales volume from profit, or segmenting the market according to classes designed specifically to treat specific forms of bacterial infections.

Alternative approaches for combatting infection could also serve as sources of innovation, including using bacteriophages or antimicrobial peptides as potential remedies. But, such measures will only be competitive against existing antibiotics if combined with advanced technologies like artificial intelligence or genome editing.

Progress has been made in this area, with funding devoted to antibiotic development increasing and competitions such as Longitude prize launched to accelerate this process. Pipeline fill-up seems to have begun with 135 promising candidates currently undergoing preclinical trials – although only one of every 15 might eventually make its way onto hospital shelves.


Biological resistance crises have highlighted the urgent need for new antibiotics, but pharmaceutical industry is struggling to make them available. Many large drug companies have abandoned research for antibiotics entirely, leaving smaller and mid-sized firms alone to shoulder this responsibility; but even these smaller firms struggled through lengthy processes of safety testing, regulatory approval and marketing approval in order to bring antibiotics onto market.

The scientific community has identified some key challenges associated with antibiotic discovery and is working toward solutions. These include overcoming basic scientific roadblocks; as well as finding better methods for identifying and targeting pathogens of concern.

One promising avenue of discovery lies in searching for novel antimicrobial compounds with unique modes of action that differ from existing antibiotics, creating different selective pressure on resistant bacteria. Another approach entails eliminating virulence factors – genetic traits which increase the probability that microorganisms cause disease in host organisms – including enzymes, secreted molecules and surface structures like lipopolysaccharides, exopolysaccharides metal-acquiring systems and two-component signaling systems.

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Phage-based methods offer another promising approach for targeting multidrug-resistant (MDR) bacteria. Phages have proven highly effective at neutralizing protein-based defences without harming normal bacterial cells or inhibiting biofilm formation; plus they have low immunogenicity so they won’t be rejected by hosts; in combination with other therapies they can increase effectiveness of treatment.

Scientists have also identified other promising avenues of discovery, including marine sponge bacterial symbionts which may house novel antimicrobial compounds that could be extracted. Researchers can isolate and study each strain individually before screening their activity against antibiotic activity to identify candidates for further testing.

MDR bacteria pose serious health consequences, making it essential to research and develop new antibiotics. This includes exploring innovative leads and approaches that could increase supply in order to close the race between antibiotic resistance and discovery of new drugs.


Since Alexander Fleming first discovered penicillin in the 1940s, antibiotics have transformed medicine and vastly improved people’s lives. Antibiotics have helped cut death from infectious diseases by over 70% while making surgical procedures safer than ever. Unfortunately, however, discoveries of new antibiotics have decreased dramatically and bacterial resistance to existing drugs has become an increasing problem.

Reasons behind the decline in antibiotic research can vary; big pharmaceutical companies have reduced or discontinued research on antibiotics because their business models no longer prove profitable, and developing an antibiotic from laboratory bench to patient bedside takes time and effort that is costly.

Restarting the pipeline of new antibiotics is of utmost importance, and scientists are diligently searching for innovative solutions. One approach being taken involves recognising global microbial diversity as an evolutionary-optimized resource for novel anti-infectives; targeting this biodiversity with advanced genomic and chemical tools; as well as devising economic models that ensure sustainable antibiotic development by sharing financial risks and profits among multiple stakeholders.

An attractive approach is the development of synthetic hybrid antibiotic-siderophore conjugates that can effectively fight Gram-negative bacteria, whose cell walls prevent most molecules from entering (see image). These compounds take inspiration from siderophores produced naturally by some bacteria as an iron carrier for transporting nutrients into cells.

Artificial intelligence (AI) is becoming more prominent in antibiotic drug discovery. A computer program created at the University of Basel recently demonstrated its ability to quickly identify antibiotic compounds that effectively target bacteria without being affected by their ability to adapt and overcome antibiotic treatment.

All these strategies will be required to combat the rapidly expanding threat of antimicrobial resistance, and must strike a delicate balance between restricting inappropriate antibiotic usage, which helps slow its emergence, and providing access to new antibiotics that treat infections caused by resistant bacteria.

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