Guest post: New ammunition in the fight against infection
Most of us have at some point in our life received a course of antibiotics to treat a bacterial infection. However, treatment options are becoming limited for many infections, as some bacteria have developed resistance to multiple antibiotics, such as the ‘superbug’ methicillin-resistant Staphylococcus aureus (MRSA), or the recently emerged totally drug-resistant (TDR) TB.
With drug resistance making bacterial infections increasingly difficult to treat, the search for new antibiotics has become more urgent than ever. This makes the discovery of acyldepsipeptides, a new class of antibiotics, very welcome indeed. Acyldepsipeptides are effective against some of the most prominent human-disease causing bacteria, including MRSA, and have attracted a great deal of attention as potential new drugs. They are distinct from all of the antibiotics currently used in the clinic as they have a novel target in the bacterial cell, as described in a paper published in PNAS.
Most antibiotics target one of four essential bacterial processes: cell wall biosynthesis; nucleic acid biosynthesis; protein synthesis; or folic acid biosynthesis (required for making DNA, RNA and proteins). Acyldepsipeptides work differently, blocking cell division – vital for bacterial survival.
Normally, bacteria multiply by dividing in two, producing identical copies of themselves. Acyldepsipeptides stop this process by binding to a bacterial enzyme called ClpP: a protease that destroys unwanted or damaged proteins. Acyldepsipeptides change the action of ClpP so that it specifically targets and destroys FtsZ, a protein that marks the site at which bacterial cell division should occur.
Destruction of FtsZ leads to the formation of long, filamentous bacteria that continue to grow but cannot divide. Crucially, this means that the bacteria cannot multiply and spread to cause infection.
The discovery of a new class of antibiotics, with a new cellular target, provides us not only with potentially lifesaving drugs, but also a glimmer of hope of unearthing yet more novel antibiotics and targets for the treatment of multi-drug resistant bacteria.
Claire is an undergraduate student at the University of East Anglia
Sass, P., Josten, M., Famulla, K., Schiffer, G., Sahl, H., Hamoen, L., & Brotz-Oesterhelt, H. (2011). Antibiotic acyldepsipeptides activate ClpP peptidase to degrade the cell division protein FtsZ Proceedings of the National Academy of Sciences, 108 (42), 17474-17479 DOI: 10.1073/pnas.1110385108