Competent bacteria will recognize

and bind naked double stranded DNA fragments present in their environment, and VX-809 in vivo translocate these fragments in a single stranded form across the membrane and into the cytoplasm. A number of genes facilitating recombination of the incoming DNA with the bacterial chromosome are also upregulated at competence, favoring the integration of the foreign DNA fragment that may permanently change the cell genotype and phenotype [9]. Competent cells are also endowed with the capacity to kill non-competent pneumococci in a mechanism named fratricide [13, 14] and this may be a key property for transformation in vivo by providing a source of free DNA. Pneumococcal fratricide is committed by cells that are competent and thus able learn more to lyse non-competent siblings [13, 15–17] with the concomitant release of DNA that will become available for transformation. The existence of two predominant CH5183284 in vitro pherotypes in S. pneumoniae and the documented occurrence

of co-colonization [18, 19], led to the proposal of two contrasting models of the pherotype impact on genetic exchange [15]. In the first model, the lack of inter-pherotype communication prevents genetic exchange between phenotypes favoring genetic differentiation [20, 21]. The second model is based on the proposal that the absence of inter-pherotype cross-activation would result in a race for competence activation with the winning phenotype inducing the lysis of cells belonging to the other pherotype [22]. The latter would result in a more frequent exchange of genetic information between different pherotype lineages that is assumed to result in enhanced genetic diversity of pneumococci. The human

host is the only natural ecological niche of all pneumococcal strains where they are exposed to the same environmental insults and share very similar lifestyles. We propose that limitations to lateral gene transfer, through a kind of “”assortative mating”" promoted by Teicoplanin the existence of two pherotypes, is creating genetically differentiated subpopulations within S. pneumoniae. Results and discussion Pherotype distribution among the pneumococcal population Traditionally, pneumococcal strains have been characterized by their capsular polysaccharide (serotype) of which pneumococci produce 91 chemically and immunologically distinct variants [23]. Although it has been shown that the serotype defines important epidemiological and virulence properties of pneumococcal isolates [24], it is also recognized that each serotype comprises different clones that may present different properties [25]. The collection of 483 invasive pneumococcal isolates was characterized for the comC allele (pherotype) carried by each isolate.