Odd enzymes as antibiotic targets
Oeiras, 04.05.2015
The haem molecule is found in all kingdoms of life, for example in humans is an important part of haemoglobin, but not all organisms obtain it the same way. Researchers from the Molecular Genetics of Microbial Resistance Lab and collaborators demonstrated that haem biosynthesis in the bacteria Staphylococcus aureus follows an unconventional path, and explored the potential of these biochemical differences as targets for novel antimicrobial agents. The work is published in Molecular Microbiology.
Staphylococcus aureus are pathogenic bacteria widely known for their increasing resistance to commonly used antibiotics therefore all singularities are worth exploring as potential weaknesses. The haem molecule is essential for these bacteria, which are able both to acquired it from the environment and synthesizing it from scratch. In the work now reported, researchers fully characterized the enzymes involved in haem biosynthesis in Staphylococcus and concluded that the biochemical pathway, named transitional pathway, lies somewhere in between the more widely known pathway and the alternative pathway active in ancient bacteria, also recently found by the authors of this study.
Staphylococcus uses enzymes different from humans, so these become possible targets for new antibiotics. To check if the biochemical differences for haem biosynthesis could be explored to fight Staphylococcus aureus, researchers screened 52 different compounds as potential inhibitors of one of the enzymes (HemY). Several compounds were shown to inhibit HemY and thus have the potential for further development. Because the transitional pathway for haem production identified in Staph is restricted to many Gram-positive bacteria, researchers propose that these enzymes may be used for selective therapy to differentiate between Gram-positive and Gram-negative pathogens.
Original Article
Molecular Microbiology (2015) Accepted Article DOI: 10.1111/mmi.13041
Staphylococcus aureus haem biosynthesis: characterisation of the enzymes involved in final steps of the pathway
Susana AL Lobo1,4, Alan Scott2,4, Marco AM Videira1, David Winpenny3, Mark Gardner3, Mike J Palmer3, Susanne Schroeder2, Andrew Lawrence2, Tanya Parkinson3, Martin Warren2 and Lígia M Saraiva1
1 ITQB
2 University of Kent, UK
3 Pfizer Global Research and Development, UK
4 Both authors contributed equally to this work and should be considered co-first authors
