Bug’s Life

Bacteria are ubiquitous microorganisms (typically in the scale of a few micro meters; a micrometer is one ten thousandth of a centimeter) that are present in almost every habitable nook and corner of earth. Some of them have even specialized for surviving seemingly uninhabitable places such as hot water springs and extremely dry or acidic environments. In an era of high personal hygiene what would amaze most of us is that there is an abounding presence of these minute life-forms in our own bodies. It is estimated that in our own bodies they outnumber our cells nearly one to ten! Most of these harmless bacteria live on our skin and inside our digestive tract. Among the advantages of harboring these bacteria are nutritional and immune system-stimulatory functions. This suggests that they are useful to us in many ways than we previously thought plausible. However, under certain circumstances such as immune depletion, these harmless bacteria can become dangerous and even fatal to the host. One notorious example is Staphylococcus aureus, which lives on our skin. It is estimated by CDC (Centers for Disease Control and Prevention), USA that S. aureus causes more infections than AIDS! Worse, this bug seems to be able to develop resistance to any drug that is thrown at it from time to time. Thus we have Methicillin Resistant Staphylococcus aureus (MRSA) and Vancomycin Resistant Staphylococcus aureus (VRSA) among others that make a substantially long list.

Watch the following video to get a grasp on the “grapes of wrath”.

More information about MRSA and the challenges it pose, is available in the following video.

So the question is what does one do if a superbug keeps developing resistance to every known antibiotic? The answers are not simple. In fact, it requires concerted action at all levels of our community as it involves both personal and policy initiatives. There are some simple steps that the public can do such as washing hands and taking care not to share personal stuff through which these bacteria spread most of the time. As for doctors, a simple step such as washing their hands after attending individual patients would decrease the risks of spreading the infection from one patient to another. Hospital management could step in and try to keep high-risk patients in isolation as S. aureus has been reported to flourish and spread in hospital environments. As for scientists like me, we have to up our ante to discover more viable targets and increase the available arsenal against these bugs. We should also try to take our discoveries from the “bench-top to the bed-side” by actively collaborating with the drug industry. Those of us with business acumen could even don the entrepreneurial hat ourselves. The demands for an ever-growing arsenal is always high in order to succeed in this fight. This is also true for a lot of other bugs as well, such as multi drug-resistant tuberculosis and AIDS.

In the beginning, screening for antibiotics was a relatively simple but laborious process where people hunted for fungal samples from soil for anything that kills bacteria in culture. In nature, several fungi produce antibiotics as means of efficiently competing with their smaller cousins for survival space, in this case soil. In the period that followed, people have successfully modified naturally occurring compounds isolated from such screens-such as penicillins-to increase their efficacy as more and more drug-resistant bugs evolved. However, we seem to have run out of steam with these approaches.

Fortunately, scientific advance provided us with alternatives. By screening synthetic combinatorial chemical libraries (such collections often contain several thousand compounds) and structure-based design principles, we can design drugs that specifically target essential proteins present inside these bugs. However, it is not easy to predict targets and perform large screens in the absence of supporting basic research. Basic research into fundamental life processes in bugs is capable of providing additional valuable targets that can be exploited for therapeutic purposes. Unique metabolic pathways and essential proteins discovered by basic researchers should provide viable antimicrobial targets for future.

The recent discovery of a potent agent against MRSA is a glaring example of the triumph of basic research, interdisciplinary approach and the entrepreneurial attitude of one scientist who lead the effort. The research group led by current director of the Institute of Cell and Molecular Biosciences, New Castle University (UK), Prof. Jeff Errington, discovered the Achille’s heel of the superbug while they were studying it’s cell division machinery. During his studies, he noticed that the rounded shape of S. aureus made it highly susceptible to the inhibition of cell division unlike some of its bacterial cousins who had a more elongated shape. He then went on to exploit these findings by starting a spin-out company Prolysis Ltd. Recently scientists from Prolysis published their findings of a novel lead compound directed against the cell division machinery of S. aureus in Science (Science. 2008, 321, pages 1673-1675). Interestingly the compound has “potent and selective anti-staphylococcal activity”. A new company Nugenis Ltd is expected to take over the drug screening opportunities emerging from the Errington lab as Prolysis evolves into a drug development company. The case serves as one more classic example where the entrepreneurial spirit of a basic researcher is set to pay big dividends for public health by taking his discovery from the “bench-top to the bed-side”.

Syam Anand

Pittsburgh, USA.