Antibiotic

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Synopsis: Pharma: Pharma generale: Drugs: Antibiotic:

#Antibiotics: Light-sensitive drugs to tackle hardy bugs The voices warning of the demise of our antibiotic defences are getting louder.

With common pathogens such as E coli and the pneumonia bug K. pneumoniae developing resistance to our antibiotics of last resort, leading pharmacologists, clinicians and epidemiologists say we risk being cast back to a time

when even routine surgery put Victorians at risk of fatal infection. It's no mystery

Complacent over-prescription of antibiotics by doctors, and their reckless, profligate use in livestock rearing, has provided ample opportunity for resistant strains of pathogenic bacteria to proliferate through natural selection.

An imminent and widespread outbreak of responsible antibiotic use seems unlikely. The financial incentive that usually drives private sector drug development is weakened by the knowledge that more profitable all-purpose antibiotics become obsolete more quickly because of the likely faster emergence of resistance.

Researchers in The netherlands are exploring a novel way forward. What if antibiotics could be deactivated after use

so that they no longer accumulate in the environment where they encourage the emergence of resistant bugs?

A team at the University of Groningen has demonstrated a way to switch off antibiotic agents after just a few hours using warmth or sunlight.

Antibiotics typically work by disrupting functions that are essential to the survival of bacterial cells.

but not for antibiotics. Organic chemist Ben Feringa at Groningen and his co-workers used an existing light-switchable unit called azobenzene,

which is all but useless as an antibiotic. Not only could this innovation prevent accumulation of active antibiotics in the environment,

but it might also help to reduce side effects. One of these comes from their indiscriminate nature:

#ACTINOGEN#Uncovering a hidden source of new antibiotics In recent years, the emergence of multiple-drug-resistant bacteria has created a major health threat, for example through hospital-acquired infections from drug

It was to meet the unaddressed need for new antibiotics that the ACTINOGEN research project began in 2005

whether genetic techniques could be used to create new antibiotics from bacteria commonly found in garden soil.

Known as streptomycetes, these bacteria were recognised already as a source of antibiotics. But a turning point came in 2002,

It was known that the bacterium produced four different antibiotics but the genome sequence revealed the potential for around 20.

The known antibiotics represented only 20%of the possible total. The genetic coding for production of the other 80%lay in'cryptic pathways,

or whether it could be used to trigger the production of new antibiotic compounds.''Meanwhile, the genomes of other streptomycete species had been sequenced

''If you wanted to discover new antibiotics, this had enormous implications, 'says Professor Dyson. During the project, ACTINOGEN scientists successfully triggered the creation of new antibiotics using the cryptic pathways of a number of streptomycete species,

thus confirming that here indeed was a rich seam of potential new drug discovery. With thousands of streptomycete species already known to science,

the potential to generate huge numbers of new antibiotics was clear. An equally important part of the project concerned the genetic engineering of a species of streptomycete

able to synthesise the new antibiotics in sufficient quantity. Known as a'generic Superhost',it allows the genetic coding for any desired antibiotic to be taken from its original bacterial host,

where the production process may be difficult and slow, and implanted in the Superhost, which then produces the antibiotic in much greater quantity than is otherwise possible.

In the past, says Professor Dyson, achieving the necessary level of production took around 10 years. The ACTINOGEN Superhost allows the same result to be achieved within six months to one year.

clearly offer the prospect of a revolution in antibiotic production opening up the possibility of a range of potential new drugs, with important benefits not only for human health,

bandages that signal when a wound is infected with antibiotic-resistant bacteria; or smart clothing that tells a runner she s getting dehydrated.##

which there are no effective antibiotics, says Timothy Lu, an associate professor of electrical engineering and computer science and biological engineering. hese bacteriophages are designed in a way that relatively modular.

which there are few new antibiotics. This group also includes microbes that can cause respiratory, urinary,

One advantage of the engineered phages is that unlike many antibiotics, they are very specific in their targets. ntibiotics can kill off a lot of the good flora in your gut,

#Future antibiotic-making kit for amateurs? Kit could one day Be led by widely available Professor Jeffrey Bode of the Institute of Transformative Biomolecules at Nagoya University in Japan,

and safely to discover novel antibiotics. Microorganisms can synthesise mixtures of complex organic molecules, such as antibiotics, from simple organic building blocks by fermentation.

Inspired by this approach, Professor Bode and his colleagues found that they could make large mixtures of biologically active compounds from a few chemical ingredients in just a few hours,

which there are no effective antibiotics, says Timothy Lu, an associate professor of electrical engineering and computer science and biological engineering.

so that simplifies that workflow in the lab."Arrayarrayone advantage of the engineered phages is that unlike many antibiotics,

"Antibiotics can kill off a lot of the good flora in your gut, "Lu says.""We aim to create effective and narrow-spectrum methods for targeting pathogens."

and other bacteria antibiotic resistance that is about 14,000 base pairs long. For 5, 000 base-pair or shorter segments,

Since the first antibacterial drugs were introduced in the 1940s bacteria have evolved ways to resist every new antibiotic that has been developed--a process that has been accelerated by the use of antibiotics in livestock to help them gain weight

and in humans to treat viral infections that antibiotics are powerless to cure. My kids are now 15 and 13

and some of the antibiotics they were given when they were little aren't given anymore

For some antibiotics the first drug-resistant bacterial strains don't appear for decades after the drug is introduced

--and can perhaps be used to target unsavory antibiotic resistance genes in bacterial pathogens and occasionally in beneficial bacteria.'

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