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Harmful bacteria selectively ‘eat’ DNA to build resistance to antibiotics.

The discovery could help prevent outbreaks of meningitis and septicaemia by keeping disease-causing bacteria susceptible to current treatments.

Research was carried out at Imperial College’s MRC Centre for Molecular Bacteriology and Infection and was published in the Proceedings of the National Academy of Sciences.

It showed that one way bacteria develop resistance to antibiotics is by ingesting free DNA from their environment. By mixing this ingested DNA with its own DNA, a bacterium can alter its genetic code, which could change it into a more resistant strain.

It’s already known that tentacles on the surface of bacteria, called pili, are responsible for ingesting molecules from the external environment. The new research, led by Dr Vladimir Pelicic, shows that pili can also bind certain DNA sequences preferentially using an electropositive stripe.

Dr Pelicic said: “Because uptake of very different DNA is often deleterious to bacteria, several species, including the human pathogen Neisseria meningitides, manage to discriminate against foreign DNA. Instead, they preferentially take up their own DNA that contains specific and short DNA signatures.”

Bacteria are likely to take up DNA for one of three reasons: as a source of food, as a template to repair damaged DNA, or to integrate the DNA with their genome and acquire new genetic traits. But the mechanism by which the DNA was preferentially ingested wasn’t known previously. Dr Pelicic said:

“In this study, we have discovered that a protein component of meningococcal pili is capable of binding DNA outside the cell using a completely novel mechanism, and sensing whether this bound DNA contains the [right] DNA signatures.

“The bound DNA is then likely to be imported into the bacteria upon retraction of the pili, which thus act like grappling hooks.”

The process of ingesting and incorporating DNA from the environment is called natural transformation and is used to share genetic traits. Dr Pelicic describes natural transformation as: “a process during which bacteria that are termed ‘competent’ ingest free DNA that is abundant in many environments and translocate it into their cytoplasm.

“The DNA is then integrated in their genomes, endowing the bacteria with new properties that are sometimes dramatic; such as high resistance to commonly used antibiotics.”

The research may lead to a new method of preventing disease-causing bacteria from becoming resistant to antibiotics. If their natural transformation mechanism could be understood and actively hindered, the bacteria for diseases such as meningitis and septicaemia could be made susceptible to antibiotics for longer.

Dr Pelicic’s research was carried out at the MRC Centre for Molecular Bacteriology and Infection which is based in Imperial College, and was set up in July 2012 with the aim of taking a multidisciplinary approach to combating disease-causing bacteria. The pooling of disciplines helped this research.

“Being part of the MRC CMBI has facilitated collaboration with Professor Steve Matthews, a co-author on the paper, who is specialized in structural biology and has helped us solve the structure of the DNA receptor,” said Dr Pelicic.

“The challenge now is to understand in greater detail the biology of these fascinating molecular machines, and – potentially – to exploit these findings to develop new drugs that would be effective against a very broad spectrum of bacteria.”

 

IMAGE: dullhunk, flickr

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