Novel antibiotic targets
The emergence of antibiotic resistant bacterial strains is an important health issue. The scientific community seems to be running out of effective antibiotics while the pharmaceutical industry is reducing the number of new antibiotics in their research and development pipeline. This clearly emphasises the need for novel anti-bacterial solutions. Scientists on the EU-funded METAL TRANSPORTERS (Mechanistic and pharmacological studies of transition-metal ABC transporters that are essential to bacterial virulence) project explored the potential of ATP binding cassette (ABC) transporters as novel antibiotic targets. ABC transporters are transmembrane proteins that utilise the energy of ATP to carry out vital biological processes including the transfer of various molecules across membranes. The consortium was particularly interested in the MntABC transporter of Bacillus anthracis, the causative agent of anthrax. MntABC is responsible for transferring various metal ions across the bacterial membrane, playing an instrumental role in virulence. Researchers compared the function of various bacterial ABC transporters to determine their structure and mechanism of action. They discovered that the different ABC transporters not only operated by role-specific mechanisms, but they also exhibited conformational memory. In addition, they validated the function of MntABC in importing manganese and discovered promising molecules that inhibited its activity. Intriguingly, zinc proved to be a potent inhibitor of MntABC, indicating that a zinc-rich diet could be the answer to treating anthrax. Collectively, the project provided fundamental insight into the structure and function of bacterial metal transporters. Considering the role of these proteins in the pathogenesis of many clinically important bacteria including Streptococcus pneumonia, Mycobacterium tuberculosis and Salmonella typhi, the findings have important clinical ramifications.
