The strange future of antibiotics

We’re publishing the shortlisted entries to the 2012 Wellcome Trust Science Writing Prize. Here, Russell Fraser on the paucity of new antibiotics and the unusual new armaments in the war against bacterial resistance.

Our current arsenal of antibiotic medications is becoming increasingly ineffective, and scientists are turning to unusual sources for new drugs. From alligator blood to cockroach brains to marijuana, chemicals are being discovered that will one day shape the future of antibiotic therapy.

The story of antibiotic resistance begins with Alexander Fleming’s discovery of penicillin in 1928. Fleming, a brilliant scientist and notorious slob, returned from a family vacation to find an improperly stored culture of bacteria contaminated with mould. In what would turn out to be a fortunate mistake, Fleming had discovered ‘mould juice,’ better known today as penicillin.

Mass production of penicillin began in earnest during World War II. Its widespread use saved many lives, but also led to the development of resistance not long after it was introduced. The pharmaceutical industry responded by developing a new drug called methicillin in 1959, but its success was short lived. A particular type of bacteria called Staphylococcus aureus quickly became resistant, and methicillin-resistant Staphylococcus aureus, or MRSA, is still a problem today. Some forms of MRSA are now resistant to all but the most potent of antibiotics. Other types of bacteria, from anthrax to gonorrhea, are catching up. These ‘superbugs’ are a serious problem, especially in hospitals, where immunocompromised patients are at particular risk for developing severe infections. In an effort to address the problem, hospitals hold in reserve certain antibiotics, with the hope that limiting their use will allow them to remain effective. This tactic has helped, but resistance to even these last-line antibiotics is emerging.

The pharmaceutical industry isn’t keeping up. Only two new classes of antibiotic have been developed in the past 40 years, in part due to the large cost of development and poor return that antibiotics generate. Some enterprising academics, however, are rising to the challenge and looking in strange places for new drugs.

The murky swamps of Louisiana in the United States are a stark contrast to the sterile, pristine environment of a scientific research laboratory, but the alligators that prowl the waters may hold some answers.

It may seem strange, but the reasoning is simple: if animals who are exposed to vast numbers of bacteria do not develop infections, they must have an effective method of fighting them off. Alligators, for example, resolve their differences using their large (and rather unhygienic) teeth. The wounds suffered rarely become infected, despite lack of access to proper healthcare, meaning that alligators must have some way of keeping the constant barrage of bacteria at bay.

This simple observation led scientist Mark Merchant of Louisiana State University to investigate further. Merchant trapped and drew blood from several alligators and from it isolated the white blood cells. He then broke the white blood cells apart and tested how well the contents killed various bacteria, viruses and fungi.

The results were surprisingly good. The extract was able to kill a wide range of bacteria and several different yeast organisms. The difficulty now is identifying exactly what it was in that extract (he suspects a protein) that was responsible for the antibiotic effect.

A similar story can be told about cockroaches. These maligned but remarkable creatures  can live for more than 45 minutes without air and inevitably encounter significant bacterial challenges scurrying around the dark and dirty crevices of our cities. But like alligators, they remain largely free from infection.

Simon Lee of the University of Nottingham discovered that a purée made from mashed cockroach brains exhibited a powerful antibiotic effect against a strain of MRSA. Like Merchant, Lee now faces the challenge of isolating and identifying the particular protein within the brain purée responsible for its antibiotic effect.

Other sources of inspiration are similarly strange, though not animal in nature. Some of the most common drugs used today, such as aspirin, are based on compounds originally derived from plants. Marijuana may not be the first plant you would think of in a search for antibiotics, but at least five of the chemicals in marijuana are able to significantly inhibit the growth of bacteria. Though still awaiting rigorous scientific investigation, cannabinoids hold definite antibacterial promise, and seem to be particularly suited for use as an ointment applied to the skin.

It’s unlikely that gator blood, roach brains or pot will ever form your next prescription, but the chemicals isolated may serve as the foundation for a much needed new class of antibiotic drug. It is somehow somewhat reassuring to know that innovative minds are identifying strange but unique additions to our arsenal in the battle against the superbugs.

References

• Moellering, R. (2011). MRSA: the first half century Journal of Antimicrobial Chemotherapy, 67 (1), 4-11 DOI: 10.1093/jac/dkr437
• Coates, A., Halls, G., & Hu, Y. (2011). Novel classes of antibiotics or more of the same? British Journal of Pharmacology, 163 (1), 184-194 DOI: 10.1111/j.1476-5381.2011.01250.x
• Darville, L., Merchant, M., Hasan, A., & Murray, K. (2010). Proteome analysis of the leukocytes from the American alligator (Alligator mississippiensis) using mass spectrometry Comparative Biochemistry and Physiology Part D: Genomics and Proteomics, 5 (4), 308-316 DOI: 10.1016/j.cbd.2010.09.001
• Merchant ME, Leger N, Jerkins E, Mills K, Pallansch MB, Paulman RL, & Ptak RG (2006). Broad spectrum antimicrobial activity of leukocyte extracts from the American alligator (Alligator mississippiensis). Veterinary immunology and immunopathology, 110 (3-4), 221-8 PMID: 16298430
• Merchant ME, Roche C, Elsey RM, & Prudhomme J (2003). Antibacterial properties of serum from the American alligator (Alligator mississippiensis). Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology, 136 (3), 505-13 PMID: 14602158
• Lee S, Duce I, Atkins H, & Khan NA (2011). Cockroaches and locusts: physicians’ answer to infectious diseases. International journal of antimicrobial agents, 37 (3), 279-80 PMID: 21269810
• Appendino G, Gibbons S, Giana A, Pagani A, Grassi G, Stavri M, Smith E, & Rahman MM (2008). Antibacterial cannabinoids from Cannabis sativa: a structure-activity study. Journal of natural products, 71 (8), 1427-30 PMID: 18681481

Russell Fraser

This is an edited version of Russell’s original essay. Views expressed are the author’s own.

Find out more about the Wellcome Trust Science Writing Prize in association with the Guardian and the Observer and read our ‘How I write about science‘ series of tips for aspiring science writers.

Over the last couple of months, we’ve published all of the shortlisted entries from the 2012 competition. Read them all, and the 2011 essays, in our archive.

Image credit: Flickr/montuschi