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Antibiotic breakthrough: Fcientists find class of drug that can kill the MRSA superbug 

A new type of antibiotic that kills hospital superbugs has been developed by scientists. 

In experiments, the drugs cured mice of notoriously difficult-to-treat, antibiotic-resistant MRSA infections.

The discovery comes as a scientists raise alarm over a global rise in antibiotic resistance, driven by over-prescription of common antibiotics. 

The Brown University researchers’ breakthrough medication may be one of a whole new group of compounds that, they hope, will have equal success in treating the dangerous infection in humans.

Researchers have developed a novel drug that may treat MRSA (pictured), an antibiotic-resistant form of staph infection that poses a major health threat to hospitals 

Better medicines have led to harder-to-beat superbugs 

For decades since the introduction of antibiotics in the 1920s, the drugs turned bacterial infections from severe illnesses to easily treatable ones. 

But as humans and our drugs have evolved, so have the bacteria. 

After encountering an antibiotic, bacteria cells may morph and change, meaning that the antibiotic attacks are no longer a good match for the pathogens they are meant to treat. 

These survivor bugs replicate, and soon a new, antibiotic-resistant ‘superbug’ is born and ready to spread among populations.

The threat posed by superbugs has been described as the ‘antibiotic apocalypse.’ 

The more antibiotics we take, the more quickly bacteria become resistant to them 

Worryingly, this threat is only made worse the more antibiotics are consumed. 

Public health experts are calling for more care to be taken, as nearly one third of antibiotic prescriptions are written unnecessarily, but antibiotic resistance is inevitable, so new drugs will eventually be essential. 

Already, a form of staph infection, MRSA (methicillin-resistant Staphylococcus aureus), has become untreatable by nearly all antibiotics. 

Around 30 percent of people carry the bacteria and in hospitals, where there is a high concentration of people – many of whom have weakened immune systems – who are more likely to come into physical contact, they are more likely to be passed to others, causing infection. 

The infection spreads and must be treated quickly, or it can cause sepsis and death. 

A new drug attacks the heart of MRSA’s survival mechanism 

But the Brown University researchers may have created a new line of defense against the superbug. 

The secret to their new drugs’ potential success could lie in them being the first to specifically target ‘persister’ cells – bacterial cells that survive the usually deadly attacks mounted against them by traditional antibiotics.

The new antibiotics work by destroying the outer layer of the bacteria – making it unlikely they will become resistant.

These drugs have a similar chemical make-up to Vitamin A and target the cell walls, or membranes, of bugs.

As conventional antibiotics are not effective in the treatment of infections caused by MRSA bacteria, novel antibacterial therapeutics are urgently required 

Dr Eleftherios Mylonakis, Brown University study author 

The researchers tested their new weapon on bacteria grown in the lab and in mice, and found the bugs were unable to hold-off the new drugs’ effects in either. 

Importantly, the rodents experienced no side effects – suggesting the discovery of a non-toxic alternative to current antibiotics. 

Dr Eleftherios Mylonakis and colleagues say they have made a breakthrough that could save lives.

The new class of antibiotics, described in the journal Nature, completely wiped out MRSA in the pre-clinical mouse model. 

They also form ‘sub-populations’ of metabolically inactive, antibiotic-tolerant ‘persister’ cells.

The researchers identified two synthetic compounds known as ‘retinoids’ that killed both growing and persister MRSA cells in tests on nematode worms.

One of these was also effective in treating a mouse model of chronic MRSA infection.

Dr Mylonakis said they work either alone or in combination with the common antibiotic gentamicin.

The researchers think it is unlikely bacteria will develop resistance to them.

The effective drugs may be two of many that could fight resistant bacteria 

The team identified the compounds – called CD437 and CD1530 – after screening the performance of about 82,000 possible molecules in stopping MRSA killing worms in experiments.

Dr Mylokanis said: ‘As conventional antibiotics are not effective in the treatment of infections caused by such bacteria, novel antibacterial therapeutics are urgently required.’

The new compounds ‘exhibit high killing rates, synergism with gentamicin and a low probability of resistance selection,’ he said.

‘With further development and optimization, synthetic retinoids have the potential to become a new class of antimicrobials for the treatment of Gram-positive bacterial infections that are currently difficult to cure.’

Currently over 4,000 natural and synthetic retinoids have been described. So it is possible that more antimicrobial candidates will be found amongst them.

In the meantime, further development of these two compounds is needed in order to improve their safety profile, and move them closer to clinical trials.

Dr Mylokanis said: ‘Despite the potential advantages of membrane-active antimicrobials such as the retinoids described here – including fast killing, low probability of developing resistance, and anti-persister activity – the major obstacle for developing retinoids as therapeutics is their potential cytotoxicity, which is a matter of considerable debate.

‘Nevertheless, we have identified a specific chemotype of membrane- active synthetic retinoids that are relatively selective for bacte rial membranes and exhibit a high level of activity towards MRSA persister cells.

‘These findings are notable because the development of appropriate antibiotics for persisters is an important unmet need.’

Dr Julian Hurdle and Dr Aditi Deshpande, of the Center for Infectious and Inflammatory Diseases at Texas A&M Health Science Center in Houston, welcomed the findings.

In a review for the journal they said: ‘Chronic infections can be hard to treat because slow-growing bacteria known as persister cells are usually unharmed by antibiotics.

‘The identification of molecules that target such cells might provide a solution.’



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