Monday, December 05, 2022

‘Game-changing’ new antibiotics could save millions from drug-resistant superbugs

MRSA: Doctor explains symptoms of the superbug

Superbugs develop when microbes develop mechanisms to protect themselves against the action of antimicrobials – or, in the specific case of bacteria, antibiotics.

The overuse of antibiotics has led to the increasing evolution of drug-resistant bacteria, with a recent review commission by the government indicating that by 2050 an additional 10 million people could die each year as a result of drug-resistant infections such as MRSA.

The situation was apparently exacerbated by the COVID-19 pandemic, which caused patients infected with SARS-CoV-2 to also be given antibiotics to control secondary bacterial infections.

Professor William Hope, director of research at the Center of Excellence in Infectious Diseases, said: “New antibiotics are urgently needed to address unmet medical needs associated with multiple and highly drug-resistant bacteria. Infections due to these superbugs compromise the treatment outcomes for many patients. ”

In their study, medicinal chemist Dr Ishwar Singh of the University of Liverpool and his colleagues focused on a molecule known as teixobactin.

Teixobactin was first identified in early 2015 after an international team of experts led by Novobiotic Pharmaceuticals studied Eleftheria terrae, a previously incurable bacterium taken from a grassland in Maine.

The researchers succeeded in reproducing the microorganism using a special piece of equipment called an isolation chip that allows bacteria to be grown in their own soil environment.

The team found that E.terrae naturally produces teixobactin to kill other bacteria living in the soil – and that it apparently belongs to a new class of antibiotics that work by inhibiting two lipid molecules that bacteria need to produce their cell walls. and maintain.

In a paper published in the journal Nature, the researchers showed that teixobactin in tests in petri dishes was highly effective against several gram-positive bacteria, including C. difficile, M. tuberculosis and the bacterium that causes anthrax, B. anthracis, cause.

Furthermore, it has been successful in the treatment of mice infected with methicillin-resistant S. aureus (MRSA) and S. pneumoniae. In fact, the dose required for 50 percent of the mice to survive MRSA was only 10 percent of that of Vancomycin, which is commonly used to treat superlice infections in hospital patients.


More powerful forms of a natural antibiotic can be used to fight drug-resistant superbugs such as MRSA (Image: Getty Images)

A Woman Takes A Pill

The overuse of antibiotics has led to increasing antibiotic resistance (Image: Getty Images)

The problem with natural teixobactin is that it is excessively expensive to manufacture on a commercial scale – but Dr Singh and his team have now shown that it is possible to create viable synthetic versions that are 2,000 times cheaper and more efficient through some of the amino acids. on the molecule for low cost, readily available alternatives.

The researchers also developed automated methods to make the new synthetic antibiotics faster – and at significantly higher yields.

Because the artificial teixobactins are stable at room temperature, they have no need for a cold chain for distribution and storage, which means they could potentially be administered in several different clinical settings around the world.

Tests have found that the simplified synthetic teixobactins can kill a wide range of bacteria that infect human patients where other antibiotics fail.

The new antibiotics have also been found to successfully eradicate MRSA in mice, accumulating at sites of infection for up to 24 hours in amounts greater than necessary to kill superbugs.

This suggests that, if clinically developed, patients with life-threatening superlice infections can be treated with just a single dose of synthetic teixobactin given daily.

READ MORE: Flurona: Patients with Covid and Flu are at greater risk of dying

The Structure Of Teixobactin

Teixobactin – the structure of which is depicted – was first identified in early 2015 (Image: public domain)

An Infographic About Mrsa

Methicillin-resistant S. aureus (MRSA) is sometimes called a ‘superbug’ (Image: Getty Images)

Dr Singh said: “Our motivation is to adapt the natural teixobactin molecule and make it suitable for human consumption. This is a journey.

“Through this project we have shown that we can make synthetic molecules at low cost and with high safety, which powerfully kills the resistant bacteria in mice.

“The introduction of synthetic diversity to generate the library of synthetic teixobactins is important in overcoming the high failure rates associated with the next stages of drug development.

“The advantage of synthetic diversity is that we can select or deselect properties and change molecules to influence strength and other desired drug-like properties.

“Our ultimate goal is to have a number of viable agents from our modular synthetic teixobactin platform that can be used as a ‘last line of defense’ against super lice to save lives that are currently lost due to antimicrobial resistance.

“Our next steps will be to focus on the central benefit of synthetic teixobactin in overcoming multi-drug-resistant bacteria in different disease models, scaling process, followed by safety tests.”

If successful, Dr Singh added, the synthetic antibiotic “could potentially be used in hospitals as a new research drug and transformed into a drug suitable for the treatment of resistant bacterial infections in humans worldwide.”

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Health Secretary Sajid Javid

Sajid Javid said: ‘It’s fantastic to see such innovative work like this happening in the UK.’ (Image: Getty Images)

Health Minister Sajid Javid said: “It’s fantastic to see such innovative work like this happening in the UK.”

This, he added, represents “another clear example of this country that is at the forefront of scientific progress that can benefit people around the world.

“The rising tide of antimicrobial resistance is threatening the future of modern medicine, with currently treatable infections becoming untreatable and routine medical procedures such as caesarean section becoming much less safe.

“Continuing to develop new drugs is critical to ensuring that this risk does not become a reality and that is why these results are so encouraging.”

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