The bacterium is commonly found harmlessly colonising the mucosal surfaces of the human nasopharynx. Z2491 and MC58 we have further characterised specific mechanisms of genetic variation in describing specialised loci for generation of cell surface protein variants and measuring the association between noncoding repeat arrays and sequence variation in flanking genes. Here we provide a detailed view of novel genetic diversification mechanisms in is a species of bacteria that is only found in humans where 1234480-50-2 supplier it is able to colonise mucosal surfaces of the 1234480-50-2 supplier nasopharynx (nose and throat). This association is normally harmless and at any one time around 15% of the population are carriers. Some strains of can cause disease by invading the host tissue leading to septicaemia or meningitis. We aim to gain understanding of the mechanisms by which these bacteria cause disease by studying and comparing genomes from different strains. Here we describe specific genes and associated repetitive DNA sequences that are involved in variation of the bacterial cell surface. The repeat sequences encourage the swapping of genes that code for variant copies of cell surface proteins. The resulting variation of the bacterial cell surface appears to be important in the close interaction between host and bacteria and the potential for disease. Introduction (the meningococcus) colonizes the nonciliated columnar mucosal cells of the human nasopharynx as a harmless commensal organism and, as such, is carried by five to ten percent of the adult population [1,2]. Some strains are able to cross the mucosa into the bloodstream from where they can cause septicaemia or meningitis and, as a result, are a major cause of disease worldwide [2]. Several genetic loci have been associated with disease [3,4], but for most strains the mechanism of virulence is not well defined. The close interaction with the human host is reflected in enriched diversity and variability at the bacterial cell surface. There are 12 different polysaccharide capsules, which are the basis of serogrouping, some of which are virulence determinants [5C7]. Vaccines targeted to the capsule types most commonly associated with disease have been successful, though capsule switching is a cause of concern [8]. Many meningococcal surface-exposed proteins and carbohydrates are also highly variable, creating a major challenge in the development of a universal meningococcal vaccine [9,10]. Current models of bacterial populations describe a spectrum of structures ranging from clonal, where lineages are derived from a common ancestor and horizontal genetic exchange plays no role, to nonclonal (or panmictic), where rates of horizontal genetic exchange are so high that genetic differences between isolates are effectively randomised and individual genetic lineages are undetectable [11]. Extremes are rare with many bacteria having a semiclonal structure where horizontal exchange is common, but groups of clonally related bacteria exist. Multilocus sequence typing has played a major role in defining bacterial INK4B population structure and shows to have a fundamentally nonclonal population due to the natural competence and high rates of recombination that characterise the species [12C14]. However, multilocus sequence typing is able to resolve into groups of related sequence types known as clonal complexes, and studies have shown that while there 1234480-50-2 supplier is enormous diversity in the population as a whole there are relatively few lineages associated with the ability to cause disease [15,16]. Most disease causing strains belong to serogroups A, B, or C, but it is clear.