The struggle to save people from MRSA, VRE-like bacteria could end with a new antibiotic compound revealed today by scientists.
In an effort to combat multidrug-resistant bacteria, researchers have created analogs of a new antibiotic that has proven to be effective against these infections. This marks a significant advancement in the fight against these dangerous infections.
Antibiotics are essential medications used to treat various bacterial diseases.
However, the misuse and overuse of antibiotics has led to the emergence of antibiotic-resistant bacteria strains, which affect millions of people globally.
To address the growing problem of antibiotic resistance, researchers are actively working on developing new antibacterial compounds that can effectively target multiple drug-resistant bacteria.
A team led by Professor Satoshi Ichikawa at Hokkaido University has published research in the journal Nature Communications that describes the creation of a highly effective antibacterial compound. This compound has been shown to be effective against a wide range of multidrug-resistant bacteria, which are becoming increasingly common.
The team focused on a class of antibacterial compounds called sphaerimicins, which block the function of a protein called MraY in bacteria.
MraY is a protein that is essential for the reproduction of bacteria, and it is involved in the synthesis of the bacterial cell wall. It is not targeted by any currently available commercial antibiotics.
Sphaerimicins are complex, biologically-derived compounds.
“We set out to design analogs to this molecule that would be easier to manufacture while also becoming more effective against MraY, thus increasing its antibacterial activity,” explains Ichikawa, a corresponding author of the study.
“The drug we designed was effective against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE), two of the more common multi-drug resistant bacteria.”
The team used molecular modeling and calculations to analyze the structure of sphaerimicin A, and then designed and synthesized two analogs called SPM1 and SPM2.
The SPM1 and SPM2 analogs demonstrated effectiveness against Gram-positive bacteria.
To further understand the mechanisms of action of SPM1 and its potential as an antibiotic, the team determined the structure of SPM1 bound to MraY and compared it to the structures of related antibacterial agents. This analysis allowed them to identify ways to simplify the molecules.
Through their analysis, the team was able to develop a simpler analog called SPM3, which showed similar activity to SPM1.
In addition to their effectiveness against MRSA and VRE, the SPMs also showed effectiveness against Mycobacterium tuberculosis, the bacteria that causes tuberculosis and can have multidrug-resistant strains.
“Our most significant contribution is the construction of the core skeleton of sphaerimicin, which can be used to develop more antibacterial agents that target MraY and hence multidrug resistant strains,” adds the author.
“Sphaerimicin is most promising as MraY is also present in Gram-negative bacteria.”
In the future, the team plans to optimize the SPM molecules that have been developed so far and to create combinations of sphaerimicins with other antibiotics to target a wider range of bacteria.
Source: 10.1038/s41467-022-35227-z
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