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Learning our ABCs: The bacteria that cause meningitis
By Bijal P. Trivedi

The complete genetic sequence of Neisseria meningitidis, group A, has just been published, only three weeks after the sequence of the closely related N. meningitidis group B. Examination of group A's sequence suggests that bacterial genomes may be far more dynamic and complex than researchers thought.

Both types cause meningitis, a dangerous infection of the covering of the brain and spinal cord, as well as septicemia, infections of the blood. While it may seem odd to invest so much research time on two such close cousins, "each strain of bacteria has it own novelties, which makes the work interesting and exciting," says Julian Parkhill, Project Manager of the N. meningitidis group A sequencing project at the Sanger Centre in Cambridge, England. The sequence is reported in the March 30 issue of Nature. The sequence of N. meningitidis B was published in Science.

Completing the sequence may lead to an immediate medical application. Although a vaccine against N. meningitidis group A exists, it is not effective in children, says Parkhill. "It is useful to sequence many strains of Neisseria to understand how similarities in genes correspond to similarities in the disease processes."

The most striking feature of this genome is the amount of repetitive DNA it contains. The group A genome is riddled with repetition. Sequences from ten to thousands of units long consisting of adenine (A), cytosine (C), guanine (G), and thymine (T), are scattered around the genome. While the function of these repeats remains unknown, Parkhill says researchers have some interesting hypotheses.

For example, this ten-letter repeat—gccgtctgaa—called an "uptake sequence," may help the bacterium pick up DNA from the environment and add it to its own genome. This is one way in which bacteria can obtain completely new genes. Other repeated sequences, more than one hundred letters long, appear to help genes move around, allowing "silent genes" to be moved next to an "on" switch where they become active.

Still other repeat sequences, like the one above but longer, may encourage rearrangement of DNA within specific genes. Proteins located on the surface of the bacterium act like distinctive clothing, signaling the immune system to attack. If the genes undergo internal reshuffling, the proteins change and each generation of bacteria presents a different appearance to the immune system, as if the bacteria were changing clothes, or donning hats and dark glasses.

Whether the repeats do actually facilitate the constant rearrangements in the genome will be left for scientists around the globe to determine, says Parkhill. Meanwhile, he and other researchers at the Sanger Centre will move on to reveal the make-up of one more pathogenic member of the N. meningitidis family. Next in line is Neisseria meningitidis group C.

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Parkhill, J. et al. Complete DNA sequence of a serogroup A strain of Neisseria meningitidis Z2491. Nature 404, 502-506 (March 30, 2000).

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