How difficult can antibiotic drug discovery be? Some of those struggling with their drug discovery projects in other areas might find themselves envying antibiotic researchers. After all, the goal is just to find a bacterial target that humans don’t have and attack it at full force. What’s more, testing the efficacy of an antibiotic just takes some relatively straightforward animal models. (Many vendors through Assay Depot can help with pharmacological models for bacterial infections.)
The reality, however, is that antibiotic drug discovery is plenty challenging. Bacteria, residents of a dog-eat-dog (or germ-eat-germ?) world where microbes brutally compete with each other for space and resources, are well-equipped to play defense, by inactivating a toxin, or pumping it outside, or one of many other ingenious devices. Surviving bacteria can pass resistance mechanisms on to progeny, or, sometimes, to neighboring bacteria through plasmids.
Bacteria have also proven to be able to put up a fight against antibiotics, much to the alarm of public health officials. The arms race with infectious bacteria requires a continuous supply of new anti-bacterial agents, but only two new classes of antibiotics have been introduced in the last three decades. Troubling statistics abound in the news. Methicillin-resistant Staphylococcus aureus (MRSA) now kills more than 18,000 people annually in the U.S. alone. The Centers for Disease Control warn that “The emergence of cephalosporin resistance, especially ceftriaxone resistance, would greatly limit treatment options and could cripple gonorrhea control efforts.” Indeed, it is not unreasonable to fear a future in which all current antibiotics are rendered ineffective.
In response, over 30 companies, universities (whose emerging role in pharmaceutical innovation has previously been discussed), and research institutes, headed by GlaxoSmithKline and Uppsala University, have teamed up in an antibiotic drug discovery effort to find new antibiotics against Gram-negative bacteria in the next six years. The endeavor, called ENABLE (European Gram-Negative Antibacterial Engine) is supported by the Innovative Medicines Initiative (IMI), a European public-private partnership aiming to make drug discovery and development more efficient.
With participants in 13 countries from diverse institutions and from a variety of disciplines, researchers in the ENABLE project will be well-positioned to join forces and combine their expertise in antibiotic drug discovery. The portfolio will be expanded through open calls for additional programs from academia and industry. ENABLE hopes to:
- Develop three antibiotic lead molecules
- Finalize the structure of two molecules for use as clinical candidates
- Advance at least one into preclinical and Phase I clinical studies
The ultimate goal: One new drug (or more) for early testing in humans by 2019. If successful, this antibiotic drug discovery collaboration may indicate that such an extensive approach is what it takes to power over the speed bumps that lie in the way of the next, desperately needed, antibiotic.
- Klevens, RM et al. 2007. Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA 298:1763-1771.