In many people, Neisseria meningitidis resides quietly in the nose or throat, doing no harm. In others, the bacterium invades and inflames the tissue that surrounds the brain and spinal cord, causing meningitis, a disease fatal in about 10 percent of cases.
This week at the Fourth Annual Conference on Microbial Genomes in Chantilly, Va., researchers announced that they have sequenced all the genes of two common strains of the microbe. Those genome data have already helped the scientists identify bacterial proteins that may lead to a much-needed vaccine for one of those strains.
Completing the bacterial genomes “is a major advance in our understanding of this important pathogen,” says microbiologist David S. Stephens of Emory University School of Medicine in Atlanta. “It’s not going to fully solve the question of how this organism causes disease, but it’s a step in the right direction.”
Although N. meningitidis comes in more than a dozen strains, three of them, A, B, and C, account for most of the bacterial meningitis worldwide. The B and C strains cause sporadic meningitis outbreaks in Europe and the Americas, while the A strain periodically unleashes devastating epidemics in Africa. In 1996 and 1997, for example, more than 200,000 Africans developed meningitis-A and around 20,000 died.
At the Chantilly meeting, scientists from the Sanger Centre in Cambridge, England, reported their recently completed sequence of the A strain. Investigators from the Institute for Genomic Research in Rockville, Md., the University of Oxford in England, and Chiron Corp. in Siena, Italy, described their sequencing of the B strain.
While it’s often difficult to identify every gene just by scanning a DNA sequence, the researchers estimate that each of the strains has more than 2,100 genes. For the B strain, only about 60 percent of those genes have an obvious function, says Richard Moxon of the University of Oxford.
Nearly 200 genes in the B strain do not appear in the A strain. Most of those genes remain a mystery, says Moxon, but a few encode toxins and other proteins that may explain why the strains affect people differently.
There’s great hope, he adds, that the genomes will lead to novel antibiotics and vaccines against N. meningitidis. Current vaccines consist of the complex carbohydrate, known as a polysaccharide, that makes up the protective capsule around the bacterium. Researchers have had to develop several vaccines because each strain has a unique polysaccharide.
For the B strain, however, there’s no capsule-based vaccine because part of its polysaccharide is identical to a human molecule. Scientists fear that immunizing people with the bacterial molecule would generate an autoimmune disorder.
Chiron has already used the B-strain genome to identify other vaccine candidates. The researchers scanned the bacterium’s genome for signs of genes that encode surface proteins or exported proteins. From about 600 leads, they confirmed a set of novel surface proteins.
When the investigators immunized mice with each of them, more than two dozen of the proteins triggered antibodies that killed N. meningitidis. The company will now evaluate whether any of those proteins can provide protection against the B strain in people.
Scientists also hope that they can develop better vaccines for other strains of the bacterium.
The current ones can’t be given to infants and don’t generate enduring immunity—their protective effect lasts about 5 years at most. Public health officials therefore wait for meningitis outbreaks before they advocate mass immunizations.
The Sanger Centre now plans to sequence strain C. The genomes should ultimately elucidate the bacterium’s biology. Moxon and his coworkers, for example, found a novel way that the B strain acquires iron from a host and unearthed several genes that may help N. meningitidis survive inside cells. “These genomes have a lot to offer,” says Moxon.