New antibiotic a ‘game changer’

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Published: Wednesday 7th January 2015 by The News Editor

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A turning point in the war against superbugs may have been reached with the discovery of a potent new antibiotic that shows no sign of inducing drug resistance.

The drug, named teixobactin, was isolated from soil bacteria using a revolutionary technique that may in future yield a rich harvest of previously hidden antibiotic compounds.

It has the ability to kill many types of harmful bacteria, including the superbug MRSA (methicillin resistant Staphylococcus aureus), by breaking down their cell walls.

Because it targets fatty molecules in the cell wall instead of proteins it is also much less likely than most antibiotics to induce microbial resistance.

In tests, scientists found no evidence of bugs evolving ways to cheat death by teixobactin, which proved harmless to mammalian cells.

British experts hailed the research as a “game changer” and “very exciting”.

Professor Kim Lewis, from Northeastern University in Boston, who led the US team, said: ” No resistance normally means that we discovere d a new detergent, which is a molecule that will destroy the membrane of the bacterial cell but also will destroy the membranes of our cells, so these are toxic compounds.

“That was my first reaction; that we found another boring molecule. But then in parallel we tested that compound against mammalian cells, and found it was not toxic against mammalian cells.

“So we have something very intriguing. Here is a new molecule that hits bacterial cells, does not hit mammalian cells, and there’s no resistance .. That was unique and very exciting.”

Teixobactin is effective against some microbes – known as “gram positive” bacteria – and not others. But the organisms vulnerable to it include some very nasty examples, such as MRSA, the TB bug mycobacterium tuberculosis, and Clostridium difficile (C. diff).

The drug will not work against “gram negative” bacteria such as Escherichia coli (E.coli) which have a kind of molecular armour plating protecting their cell membranes. Gram negative bacteria pose one of the greatest antibiotic resistance challenges.

However the research goes much further than identifying one promising new drug. It potentially opens the door to further discoveries that could boost the world’s antibiotic arsenal and turn the tide against the superbugs.

Most antibiotics are derived from soil bacteria and fungi, which use them as weapons in an on-going battle for survival with other micro-organisms. But many remain hidden from science, because 99% of the simple life forms producing them refuse to grow in laboratory Petri dishes. This makes them difficult to study and screen for new products.

Prof Lewis and his team tried a new tack by growing bacteria in the place they know best, the soil. Diluted soil samples containing the bugs were placed in culture wells sandwiched between two semi-permeable membranes and buried in earth.

Speaking on a podcast issued by the journal Nature, which published the research, the professor said: “Essentially we trick them because .. they think it’s their natural environment and pretty much everything grows.

“Now we can isolate them, study them, and access antibiotics if they are producing them.”

Using this technique, the scientists obtained 50,000 isolates from 10,000 soil bacteria strains, from which they identified 25 new antibiotics including teixobactin.

In mice, the drug proved highly effective against MRSA and Streptococcus pneumoniae, which causes major infections of the lungs and blood poisoning.

The drug works in a similar way to the “last resort” antibiotic vancomycin, discovered in 1953, which also breaks down the cell walls of gram positive bacteria.

It took almost 40 years for bacteria to start becoming resistant to vancomycin. Because of its mode of action, which involves binding to multiple molecular targets, scientists believe it will take even longer for genetic resistance to teixobactin to emerge.

Last year the World Health Organisation warned that a “post-antibiotic” era was rapidly approaching in which common infections can no longer be tackled with tried and trusted drugs, turning the clock back to a time when even a slight cut or graze might prove fatal.

The Government’s Chief Medical Officer Dame Sally Davies has said antibiotic resistance poses a “catastrophic threat” on a par with terrorism and climate change.

Commenting on the research, microbiologist Professor Laura Piddock, from the University of Birmingham, said: “The screening tool developed by these researchers could be a game changer for discovering new antibiotics as it allows compounds to be isolated from soil producing micro-organisms that do not grow under normal laboratory conditions.

“If teixobactin can be formulated into a new drug for patients, it could be used to treat infections such as tuberculosis or those caused by MRSA.”

Infectious disease expert Professor Mark Woolhouse, from the University of Edinburgh, said: “Any report of a new antibiotic is auspicious, but what most excites me about the paper by Lewis et al. is the tantalising prospect that this discovery is just the tip of the iceberg ..

“It may be that we will find more, perhaps many more, antibiotics using these latest techniques. We should certainly be trying – the antibiotic pipeline has been drying up for many years now. We need to open it up again, and develop alternatives to antibiotics at the same time, if we are to avert a public health disaster.”

Professor Roger Pickup, associate dean of research at the University of Lancaster, said: “This is a very exciting development. This may lead to the discovery of more unique antibiotics that can come on line and replace, or work in tandem, with current therapies that fight infection, particularly those caused by bacteria currently resistant to the spectrum of antibiotics available to us at present.”

Professor Neil Woodford, head of Public Health England’s Antimicrobial Resistance and Healthcare Association Infections Reference Unit, said: “The rise in antibiotic resistance is a threat to modern healthcare as we know it so this discovery could potentially help to bridge the ever increasing gap between infections and the medicines we have available to treat them.

“Taking any potential antibacterial compound from discovery to successful licensing is a long, costly and difficult process. However it is one that needs to be encouraged while we tackle other elements that contribute to the development of antibiotic resistance and seek to preserve the antibiotics we do have.”

Published: Wednesday 7th January 2015 by The News Editor

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