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Researchers pinpoint mutations that give bacteria antibiotic resistance

Researchers Prof. Kentaro Miyazaki (left) and Dr Kei Kitahara (right) hope their discovery can contribute to the development of a database for the detection and diagnosis of resistant bacteria. (Photographs: Hokkaido University)

Thu. 16. August 2018


HOKKAIDO, Japan: In a recent study, researchers in Japan have developed a new way of testing bacterial resistance to antibiotics and while doing so found three previously unknown resistance mutations. With more and more pathogenic microorganisms developing immunity to widely used antibiotics, the discovery could be reassuring for many health professionals.

The researchers, from Hokkaido University and the National Institute of Advanced Industrial Science and Technology, have developed an approach to systematically screen for resistant ribosomal RNA (rRNA) genes. RRNA is the indispensable part of the cell that creates proteins. It is one of the primary targets of antibiotics, but rRNA mutation is now a well-known route to resistance. That resistance has many healthcare professionals concerned. In a recently presented study at EuroPerio9 in Amsterdam titled, “Antibiotic resistance trends in human periodontitis microbiota (2008–2015)”, results showed that antimicrobial resistance is on the rise among German patients with severe periodontitis.

Dr Kei Kitahara, a molecular microbiologist at Hokkaido University and co-author of the current paper, said: “Our results suggest that there are many unfound and uncharacterised antibiotic resistance point mutations in rRNA genes.”

In order for Kitahara and co-author Prof. Kentaro Miyazaki to arrive at this conclusion, they took rRNA from a wide range of bacterial species in the natural, or non-clinical, environment, where mutations are continually taking place. From there, the researchers were able to insert them into inactive Escherichia coli lacking in rRNA and found that more than 2,000 imported rRNA could compensate for this lack, thereby preventing the E. coli from dying. They then tested whether a common antibiotic, spectinomycin, effectively killed the bacteria or if the rRNA gave the E. coli resistance.

According to the study results, the screening found three previously unreported mutations in rRNA from the pathogens that resisted the antibiotic, along with other mutations that were already known. Although using inactive E. coli to test for mutations has been proposed before, this screening can analyse rRNA from other pathogens rather than just what is present in the E. coli.

The discovery by the researchers comes at a time when antibiotic research is becoming increasingly challenging.  Earlier this year, the Star Tribune reported that Novartis, a Swiss multinational pharmaceutical company based in Basel, was the latest drug-manufacturing giant to announce it was shutting down its antibiotics and antiviral research programmes. According to the article, a Novartis representative said the move would allow the firm to “prioritise resources in other areas where we believe we are better positioned to develop innovative medicines”.

Looking to the future and possible next steps, Kitahara said: “We hope our method could be used to verify antibiotic resistance mutations, and contribute to the development of a database for the discovery and diagnosis of resistant bacteria.”

The study, titled “Functional metagenomic approach to identify overlooked antibiotic resistance mutations in bacterial rRNA”, was published in Scientific Reports on 3 April 2018.

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