Studies on Haemproteins of Gram-positive Bacteria - Implications as Antibacterial Drug Targets

Abstract: With the discovery of antibiotics, several diseases that were previously lethal is today readily cured, or so we thought. Some degree of resistance to one or several antibiotics can be found among many strains of clinical important bacteria. The problem has been somewhat kept at bay for the last few decades by altering already existing antibiotics, and thereby prolonging their usage. It is clear that there is an urgent need to develop new strategies in designing novel antibacterials and to find new drug targets in attempts to overcome bacterial resistance. This report will review haem containing proteins, their function and relevance to gram-positive bacteria and their possible role as novel antibiotic drug targets. Haemproteins can be found in virtually all living organisms and often have important functions. All haemproteins possess one or more of the iron containing cofactor haem but can otherwise be very diverse. Three groups of haemproteins have been looked at in more detail. The first is truncated haemoglobin, a group belonging to the globin superfamily with intriguing ligand-binding capabilities and a possible function in NO resistance. The second is a novel haem binding protein that is involved in the maturation pathway of covalent haem attachment to cytochrome c in gram-positive bacteria. The last one is cytochrome bd, an alternative terminal oxidase unique to bacteria that is used during low oxygen tension. None of these three haemproteins can be found in a human host. The work done on these three proteins is discussed to assess the plausibility for these haemproteins to act as drug targets.