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Study Finds Few Core Virulence Genes Among Meningitis Bacteria Strains

NEW YORK (GenomeWeb News) – Many genetic variations — not just a core set of virulence factors — are associated with pathogenic strains of a meningitis bacteria, German scientists reported today.
 
Researchers at the Universities of Wurzburg and Bielefeld and MWG Biotech used sequencing and comparative genomics to try to understand what makes some strains of Neisseria meningitidis infectious and others harmless. Their results appeared today in the online, early edition of the Proceeding of the National Academy of Sciences.
 
Meningitis, the infection and inflammation of the membrane covering the brain and spinal cord, can be caused by many different bacteria or viruses. In general, meningitis is characterized by a sudden high fever, stiff neck and, in some cases, an aversion to bright lights. Though antibiotic treatments are available for some types of bacterial meningitis, it can lead to brain damage, hearing loss, or death.
 
Today, N. meningitidis is among the most frequent bacterial meningitis culprits. Even so, the bug is surprisingly common. Around ten percent of healthy people carry it in their upper throat and nasal passage without developing an infection.
 
Despite the hundreds or even thousands of N. meningitidis strains out there, most research has focused on the most dangerous strains. These virulent strains tend to be surrounded by a sugary capsule. Beyond this, though, it’s unclear why some strains become invasive and dangerous and others don’t.
 
In an effort to tease apart genetic differences, lead author Christoph Schoen, a microbiologist at the University of Wurzburg, and his colleagues sequenced three N. meningitidis strains, isolated from asymptomatic children and young adults in Bavaria, Germany, using whole-genome shotgun sequencing with between eight and ten times coverage.
 
They compared these draft genomes of so-called “carriage strains” with the genomes of three disease-causing strains using pairwise BlastN alignments and the Artemis Comparison Tool. To hone in on the potentially harmful sequences — the pathogenome — they focused on genes that were present in harmful strains but absent in the strains commonly carried without symptoms.
 
Their results suggest that the meningococcal genome is widely variable, with a core genome consisting of around 1,337 genes. According to this study, each new strain has about 43 new genes of its own that do not belong to this core genome.
 
“[N]ew genes continue to be added to the gene pool of N. meningitidis any time a new strain is sequenced,” the authors wrote. “Therefore, the construction of a ‘pan-Neisseria’ microarray capturing the entire meningococcal gene pool might be an elusive goal.”
 
The team also failed to find a core set of pathogenicity genes. In fact, the comparative genomics approach tentatively cleared a large percentage of suspicious genes. All but 19 of the 134 genes previously associated with virulence were found in both the virulent and carriage strains. And only one of these is present in all disease-causing N. meningitidis strains sequenced.
 
“[O]ur data suggest that, in N. meningitidis, most of the so-far-studied candidate virulence genes should more appropriately be considered as fitness genes,” the authors wrote, “and not as virulence factors for the invasion of host tissue.”
 
Within the N. meningitidis genome, they frequently detected chromosomal rearrangements, including translocations and deletions. For instance, disease-causing strains tended to have large symmetrical inversions at the origin of replication.
 
The authors suggest that the most virulent strains may have acquired the genes for the polysaccharide coat associated with virulence via horizontal gene transfer with other bacteria in the nasal passage and upper throat. As well, they speculate that variation in genes governing interactions between bacterial and host cells may influence virulence. And, they suggest, SNP maps may reveal this variation as future N. meningitidis genomes are sequenced.
 

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