A team led by Professor Satoshi Ichikawa at Hokkaido University has been working on the development of new antibacterial substances. Their most recent study, published in the journal
details the development of a highly effective antimicrobial compound that is effective against the most common multidrug-resistant bacteria.
The team studied an antibacterial compound called sphaerimicin. These compounds block the function of a protein in bacteria called MraY. MraY is essential for bacterial replication and plays a role in bacterial cell wall synthesis; nor is it the target of commercially available antibiotics.
What is Sphaerimicin?
“Sphaerimicin are biological compounds and have a very complex structure,” explains Ichikawa, a corresponding author on the study. “We set out to design analogues for this molecule that would be easier to manufacture while also becoming more effective against MraY, thereby increasing its antibacterial activity.”
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The team analyzed the structure of sphaerimicin A using a computationally supported molecular model, and designed and synthesized two analogues of sphaerimicin, SPM1 and SPM2. These analogs have been found to be effective against gram-positive bacteria.
They then determined the structure of SPM1 bound to MraY. By studying this structure and comparing it with the structures of related antibacterial agents, they identified a way to further simplify the molecules. They succeeded in developing a simpler analog, SPM3, which has similar activity to SPM1.
In addition to being effective against MRSA and VRE, SPM is also effective against Mycobacterium tuberculosis, tuberculosis bacteria and multidrug-resistant strains.
Ichikawa concludes: “Our most important contribution has been to build the core framework of sphaerimicin, which can be used to develop more antibacterial agents that target MraY and thus multidrug-resistant strains. Sphaerimicin. most promising because MraY is also present in gram-negative bacteria”. . Future work will include optimizing SPM molecules currently under development and developing antibiotic combinations containing sphaerimicin to target a wider range of bacteria.
Source: Eurekalert
