First proof a synthesized antibiotic is capable of treating superbugs

A "game changing" new antibiotic which is capable of killing superbugs has been successfully synthesised and used to treat an infection for the first time - and could lead to the first new class of antibiotic drug in 30 years. The breakthrough is another major step forward on the journey to develop a commercially viable drug version based on teixobactin - a natural antibiotic discovered by US scientists in soil samples in 2015 which has been heralded as a "gamechanger" in the battle against antibiotic resistant pathogens such as MRSA and VRE.

Scientists from the University of Lincoln, UK, have now successfully created a simplified, synthesised form of teixobactin which has been used to treat a bacterial infection in mice, demonstrating the first proof that such simplified versions of its real form could be used to treat real bacterial infection as the basis of a new drug.

The team at Lincoln developed a library of synthetic versions of teixobactin by replacing key amino acids at specific points in the antibiotic's structure to make it easier to recreate. After these simplified synthetic versions were shown to be highly potent against superbug-causing bacteria in vitro - or test tube - experiments, researchers from the Singapore Eye Research Institute (SERI) then used one of the synthetic versions to successfully treat a bacterial infection in mice.

As well as clearing the infection, the synthesised teixobactin also minimised the infection's severity, which was not the case for the clinically-used antibiotic, moxifloxacin, used as a control study. The findings are published in the Journal of Medicinal Chemistry.

It has been predicted that by 2050 an additional 10 million people will succumb to drug resistant infections each year. The development of new antibiotics which can be used as a last resort when other drugs are ineffective is therefore a crucial area of study for healthcare researchers around the world.

Dr Ishwar Singh, a specialist in novel drug design and development from the University of Lincoln's School of Pharmacy, said: "Translating our success with these simplified synthetic versions from test tubes to real cases is a quantum jump in the development of new antibiotics, and brings us closer to realising the therapeutic potential of simplified teixobactins.

"When teixobactin was discovered it was groundbreaking in itself as a new antibiotic which kills bacteria without detectable resistance including superbugs such as MRSA, but natural teixobactin was not created for human use.

"A significant amount of work remains in the development of teixobactin as a therapeutic antibiotic for human use - we are probably around six to ten years off a drug that doctors can prescribe to patients -- but this is a real step in the right direction and now opens the door for improving our in vivo analogues."

Dr Lakshminarayanan Rajamani from SERI added: "We need sophisticated armour to combat antibiotic-resistant pathogens. Drugs that target the fundamental mechanism of bacterial survival, and also reduce the host's inflammatory responses are the need of the hour. Our preliminary studies suggest that the modified peptide decreases the bacterial burden as well as disease severity, thus potentially enhancing the therapeutic utility."

The work builds on the success of the Lincoln team's pioneering research to tackle antimicrobial resistance over the past 22 months to turn teixobactin into a viable drug. The team will now develop a bigger library of simplified synthetic versions which can be used is a diverse number of applications, advancing the goal of a clinical drug.

Anish Parmar, Rajamani Lakshminarayanan, Abhishek Iyer, Venkatesh Mayandi, Eunice Tze Leng Goh, Daniel G Lloyd, Madhavi Latha S Chalasani, Navin K Verma, Stephen H Prior, Roger W Beuerman, Annemieke Madder, Edward J Taylor, Ishwar Singh.
Design and Syntheses of Highly Potent Teixobactin Analogues against Staphylococcus aureus, Methicillin-Resistant Staphylococcus aureus (MRSA), and Vancomycin-Resistant Enterococci (VRE) in Vitro and in Vivo.
J. Med. Chem., 2018, 61 (5), pp 2009-2017. doi: 10.1021/acs.jmedchem.7b01634.

Most Popular Now

Delivering insulin in a pill

Given the choice of taking a pill or injecting oneself with a needle, most of us would opt to regulate a chronic health condition by swallowing a pill. But for millions o...

Probiotics can protect the skeletons of older wome…

For the first time in the world, researchers at the University of Gothenburg, Sweden, have demonstrated that probiotics, dietary supplements with health-promoting bacteri...

Alzheimer's breakthrough: Brain metals that may dr…

Alzheimer's disease could be better treated, thanks to a breakthrough discovery of the properties of the metals in the brain involved in the progression of the neurodegen...

Can aspirin treat Alzheimer's?

A regimen of low-dose aspirin potentially may reduce plaques in the brain, which will reduce Alzheimer's disease pathology and protect memory, according to neurological r...

FDA approves first drug comprised of an active ing…

The U.S. Food and Drug Administration today approved Epidiolex (cannabidiol) [CBD] oral solution for the treatment of seizures associated with two rare and severe forms o...

In mice, stem cells seem to work in fighting obesi…

Obesity is an increasing global health problem associated with several comorbidities and a high risk of mortality. A wide spectrum of interventions has been proposed for ...

FDA takes steps to foster greater efficiency in bi…

Today, the agency withdrew the draft guidance, "Statistical Approaches to Evaluate Analytical Similarity," issued in September 2017. The draft guidance, if finalized as w...

Research shows how a moderate dose of alcohol prot…

For at least 20 years, research has shown that for many people, moderate consumption of alcohol can protect the heart, but the reason for this is poorly understood. A stu...

Some existing anti-cancer drugs may act in part by…

Bolstering the notion that RNA should be considered an important drug-discovery target, scientists at Scripps Research have found that several existing, FDA-approved anti...

'Kiss of death' cancer

It's called the 'kiss of death'. Triple negative breast cancer has no targeted drug therapy and, as such, the only hope for these patients is chemotherapy. Triple negativ...

Novartis Clear about Psoriasis survey data highlig…

Novartis announced today the publication of global Clear about Psoriasis survey data in the Journal of the European Academy of Dermatology and Venereology[1]. The publica...

Poliovirus therapy for recurrent glioblastoma has …

A genetically modified poliovirus therapy developed at Duke Cancer Institute shows significantly improved long-term survival for patients with recurrent glioblastoma, wit...