New antimicrobials

Overcoming antimicrobial resistances

The COVID-19 pandemic has been powerful in revealing to the public what a major threat infectious diseases can be to humanity. But this is not news to specialists. Like the coronavirus SARS-CoV-2, many other microorganisms (viruses, bacteria, fungi and parasites) could lead to similar situations if no treatment is available to counter them. The problem is, while antimicrobials do exist, our misuse of these treatments has led to the rise of resistance mechanisms in some microorganisms, which means that today many are no longer sensitive to the drugs scientists had so successfully developed over the past century. By exploiting the immense potential of microbial dark matter, DEINOVE is developing new antimicrobials to overcome these resistances.

The World Health Organization (WHO) first sounded the alarm on the rising threat of antimicrobial resistance (AMR) in 2001 [1] , but little has been achieved to contain the issue since then. In the United States alone, at least 2.8 million people contract an antibiotic resistant infection every year, and more than 35’000 people die from it [2]. The situation is not much better in Europe where each year, more than 670’000 infections occur due to antibiotic resistant bacteria, and approximately 33’000 people die as a direct consequence of these infections [3]. Following the current trend, experts anticipate multiresistant microbes (called superbugs) could kill 10 million people around the world in the year 2050 alone, which is more than do road accidents or cancer today [4].

Superbugs to kill “more than cancer” by 2050

New antimicrobials are desperately needed to address the major concern that is AMR. To take bacterial infections as an example, over 100 antibiotics have been developed since 1928 when the first antibiotic, penicillin, was discovered. Antibiotics are either bactericides or bacteriostatic, which means that they kill bacteria or inhibit their growth, and they act to inhibit different functions of bacterial cells. For example, beta lactams, like penicillin, inhibit synthesis of the bacterial cell wall, quinolones interfere with bacterial DNA synthesis, and tetracyclines inhibit bacterial protein synthesis. But most of these antibiotics belong to only just over 20 different chemical families which were discovered between 1929 and 1962. Since then, new antibiotics have resulted from synthetic modifications of pre-existing ones and only 3 new classes have been discovered (oxazolidinones, lipopetides, and malacidins).

Timeline of antibiotic discovery

Timeline of antibiotic discovery

Although synthetic chemistry has undoubtedly been crucial for developing successive evolutions of known antimicrobials, the vast majority of these drug classes were originally discovered as natural compounds produced by living microorganisms. But once the golden age of antibiotic discovery was over in the 1960s, scientists abandoned the search for antimicrobials in bacteria due to high rates of rediscovery. Recent technological advances – cultivation strategies, high throughput sequencing, progress in mass spectrometry – mean  that biodiversity can now be explored in a whole new way: previously overseen species can now be detected and even sometimes cultivated, the products of their metabolism are more easily identified and their production can be optimized. By making use of these tools, DEINOVE is now able to accelerate the research and development of new antimicrobials, searching within the endless reservoir of molecules held by microbial dark matter.

To support its development, the company benefits from a favorable economic and regulatory environment. Aware of the limitations of a model (that seeks to preserve the effectiveness of new antimicrobials by limiting their prescription and thereby limiting the size of their market, French and international institutions have implemented incentives to support R&D efforts of the most innovative companies, providing a known return on investment and rewarding successful developments. In this framework, DEINOVE’s AGIR program benefited since its launch in 2017 from the support of the French government through its “Investissements d'Avenir” program.

 

[1] WHO Global Strategy for Containment of Antimicrobial Resistance. 2001

[2] Antibiotic resistance threats in the united states. US Department of Health and Human Services. Center for Disease Control and Prevention. 2019

[3] Surveillance of antimicrobial resistance in Europe. Annual report of the European Antimicrobial Resistance Surveillance Network (EARS-Net). 2018

[4] Tackling Drug-Resistant Infections Globally: Final Report And Recommendations The Review On Antimicrobial Resistance Chaired By Jim O’neill. Welcome Trust and the UK Department of Health.May 2016