MGBs: Bacteria’s worst nightmare?
Craig McInnes writes about a recently commercialised antibacterial and touches on the need for new antibiotics.
2010 saw the first steps towards a potential new treatment of bacterial infections. Minor Groove Binders (MGBs) developed at the University of Strathclyde have recently been licensed out to the Scottish start-up company MGB Biopharma Ltd. The company have been tasked with commercialising at least one of six new antibiotics and have recently raised nearly £2million to take the compounds through scale-up, formulation and eventually onto human testing. So what are MGBs and why are they so important in the fight against ‘bad bacteria’? Indeed, why do we even need new antibiotics at all?
Why are bacteria a cause for concern?
Bacteria such as Methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli) have shown significant resistance to several antibiotics, including the classic and much over-used beta-lactams (which are commonly known as penicillin type drugs). In addition there have also been several accounts of vancomycin resistant-MRSA 1. This is alarming, as vancomycin is typically the last defence against resistant strains of bacteria. As a result this doubly resistant strain of bacteria could cause infections which are far more difficult to treat.
Whilst the tenacity of these infections is challenging enough, the frequency of the infections amongst hospital patients is also a cause for concern. These bacteria typically cause more serious infections when exposed to open wounds and spread much faster amongst the weak, the old or those with poor immune systems. Therefore, it comes as little surprise to find that a huge amount of effort, both industrially and academically, is being made towards the eradication and containment of bacterial borne infections.
How can we hope to treat these infections?
MGBs are at the centre of ongoing research into anti-infective agents as they are able to bind to bacterial DNA. This subset of DNA targeting compounds are able to bind to the minor groove during replication and halt bacteria from reproducing. Inspired by naturally occurring compounds such as Netropsin and Distamycin which bind to Short ‘AT rich’ patterns, MGBs can be tailored to bind to specific base pair patterns within DNA. This affords chemists the opportunity to specifically target resistant bacteria. Bacteria such as MRSA can become resistant to traditional antibiotics with only one mutation in their DNA but tend not to grow large colonies. However, an additional mutation allows them to thrive. These mutations can be the target for new DNA binding drugs.
The compounds under investigation at MGB Biopharma are in late stage pre-clinical development and have demonstrated significant in vitro (non-animal studies) and in vivo (animal studies) activity against a range of bacteria, including MRSA. Such compounds could be vital in helping researchers discover new ways to treat infections as their mode of action is entirely novel. Dr Miroslav Ravic, the company’s CEO observes that “…MGB Biopharma has the potential to bring a new mechanism of action into the treatment of serious hospital and community acquired infections. This is an area of high demand as a result of the rise of resistant bacteria which are not susceptible to many currently available antibacterial products”.
Bacteria retain their resistance longer than originally thought.
The fact that the medical community could have a new tool to fight bacterial infections is significant. When we consider just how long some bacteria can retain genes which allow them to be resistant to antibiotics, we see that eradication of this resistance might not simply disappear with time. Streptomycin-resistant E. coli can still be found in children despite the fact that streptomycin has not been in use for over 30 years – which equates to around 60,000 generations of bacteria. So while it is a good idea to limit our exposure to antibiotics unless absolutely necessary (thus preventing resistance), the more methods we have to tackle the problem the better. This allows doctors to ‘keep ‘an ace up their sleeves’.
Professor Colin J. Suckling, the principal investigator at the University of Strathclyde, understands all too well the importance of new approaches in tackling this problem and sees this Scottish-led solution as a significant step in combating this greater issue. “Minor Groove Binders, which are found in DNA structures, have great potential to act as anti-infective agents to deal with infections which can have a serious, and even fatal, impact. We look forward to the new company taking the technology further so that improved and safer treatments can be delivered to patients”.
What next for MGBs?
The potential for these compounds is only beginning to be exploited. Those who are familiar with the field will be aware that they are attracting interest within the field of oncology which could be expanded to other fields, including anti-parasitics and anti-fungals. It could also be used to bind to anything with DNA so long as it is not common in humans.
While MGB Biopharma is still in the early stages of drug development, the potential exists for a new and exciting field to become well established, which could have global repercussions. Hopes are high for MGBs and their developers are keeping a keen eye on the past as Dr Miroslav Ravic has reflected;
“…the last Scottish association with the discovery of a new antibacterial class was none other than that of Sir Alexander Fleming’s discovery of penicillin 82 years ago.”
