Fishing for Signals
Scanning electron micrograph of Methicillin-resistant Staphylococcus aureus (MRSA) and a dead Human neutrophil. Credit: NIAID.
Staphylococcus bacteria is the leading cause of skin infections. Especially Methicillin-Resistant Staphylococcus Aureus (MRSA) is problematic, as even minor infections can have severe health consequences, e.g. blood poisoning.
The ability to cause disease in humans of both harmless and antibiotic-resistant staphylococci is controlled by signalling molecules produced by the staphylococci themselves. There are many indications that the communication between these signalling molecules affects MRSA bacteria’s ability to cause infection.
Now researchers at the University of Copenhagen have developed a new method that offers far greater understanding of the signalling molecules of staphylococci. A greater understanding of the signalling molecules may make it possible to prevent staphylococci from causing infection, regardless of whether or not the staphylococci are resistant.
‘This method enables us to determine exactly what staphylococcus signalling molecules look like. The signalling molecules tell us how staphylococci communicate and when they shift from harmless colonisation to a condition where they are dangerous and produce toxins resulting in infection’, says Professor Hanne Ingmer from the Department of Veterinary and Animal Sciences.
’Fishing Method’ Makes Analysis Easier
For about 20 years, researchers have known that staphylococci communicate with each other through chemical transmitter substances called autoinducing peptides (AIPs). AIPs are only found in very small concentrations around staphylococcus bacteria, and they vary greatly in composition. Therefore, it has been difficult for researchers to study them more closely.
‘Using chemistry, mass spectrometry and gene sequence analysis, we have developed a method that enables us to efficiently and easily ’fish’ for and extract these AIPs from very complex mixtures. This way, we are able to increase the very small amounts of AIPs so we can detect them with stadard equipment and further study them,’ says the last author of the study Christian Adam Olsen, professor at the Department of Drug Design and Pharmacology.
Until now, only around 10 of these APIs had been identified. Using the new ‘fishing method’, the researchers have more than doubled this number. The more signalling molecules that can be identified, the better researchers will be able to determine how and why staphylococci cause infection.
‘We are far from treatment in humans, but along the way we hope to conduct trials on animal models. It is still too early to say whether we can reprogam the staphylococci bacteria with modified AIPs in a way where they no longer attack humans by producing toxins', says Christian Adam Olsen.
This article has been republished from materials provided by the University of Copenhagen. Note: material may have been edited for length and content. For further information, please contact the cited source.
Identification of autoinducing thiodepsipeptides from staphylococci enabled by native chemical ligation. Bengt H. Gless, Martin S. Bojer, Pai Peng, Mara Baldry, Hanne Ingmer & Christian A. Olsen. Nature Chemistry, volume 11, pages463–469 (2019), https://doi.org/10.1038/s41557-019-0256-3.
A large clinical trial to assess treatments for preventing people at high risk from developing multidrug-resistant tuberculosis (MDR-TB) has begun. The study is comparing the safety and efficacy of a new MDR-TB drug, delamanid, with the decades-old TB drug isoniazid for preventing active MDR-TB disease in children, adolescents and adults at high risk who are exposed to adult household members with MDR-TB.READ MORE