Sunday, 15 July 2018

New class of antibiotics to combat drug resistance


A new class of antibiotic has been discovered. The chemical kills bacteria by binding to ribosome. This disrupts protein synthesis, and stops the microbial cell from replicating. This is a step forward in the search for new antimicrobials.

Scientists from the University of Illinois at Chicago have highlighted a potential new class of antibiotics. These compounds appear effective at treating a range of current antimicrobial drug-resistant infections.

The new class of antibiotics, called odilorhabdins, are promising for two reasons. Firstly, the compound has a distinct way of killing bacteria. Secondly, the source of the compound is unusual. This strengthens the podetial use, should the compound be commercialized, for tackling hard-to-treat bacterial infections.

In terms of the atypical source for the chemicals, they are produced by symbiotic bacteria found only in soil-dwelling nematode worms. The bacteria colonize insects for food, and they also provide a degree or protection from bacteria that are pathogenic to the worms. This protection is through secreting the antibiotic.

In the last two decades, the speed at which bacteria are becoming resistant to current antibiotic treatments has significantly increased. This shift is threatening the ability of medical staff to carry out routine operations or organ transplants in the future. The problem has been compounded by microorganisms acquiring resistance to one antimicrobial or another, leading to multi-drug resistant microorganisms (the so-termed ‘super bugs’); and by the misuse of antibiotic by medical staff (improper prescribing) and farmers (in seeking leaner meats). The consequence has led to an imperative to finding new and effective antimicrobials.

As part of the process to find the new antibiotic, microbiologists screened 80 cultured strains of the bacteria for antimicrobial activity. Next, they isolated the active compounds, and proceeded to study their chemical structures. From this the researchers engineered more potent derivatives.

According to lead researcher Yury Polikanov there’s something important in the way that odilorhabdins kill bacteria: “Like many clinically useful antibiotics, odilorhabdins work by targeting the ribosome… but odilorhabdins are unique because they bind to a place on the ribosome that has never been used by other known antibiotics.”

With this mechanism, when odilorhabdins are introduced to the bacterial cells they impact the reading ability of the ribosome and this causes the ribosome to make mistakes as it creates new proteins. Trials to date have shown good effectiveness of the antibiotic against carbapenem-resistant Enterobacteriacae, a group that contains several antimicrobial resistant members.

The research has been published in the journal Molecular Cell. The research paper is titled “Odilorhabdins, Antibacterial Agents that Cause Miscoding by Binding at a New Ribosomal Site.”

Posted by Dr. Tim Sandle, Pharmaceutical Microbiology

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