On the other hand, serotype 4 presents one PFGE cluster that was significantly associated with CSP-2, whereas no association was found at the serotype level possibly as a consequence of the largest cluster of serotype 4 being mainly CSP-1 [see Rigosertib nmr Additional file 2 - Table S2]. Taken together the data suggest that pherotype is a clonal property that may vary independently of the serotype. Table 2 Odds ratios measuring significant associations between pherotype and serotype. Serotype CSP-1 CSP-2 OR (95%CI)a FDRb 1 48 2 11.434 (2.923;98.526) < 10-4 3 23 23 0.375 (0.193;0.729) 0.017 6A 2 11 0.071 (0.007;0.330) 0.001 9N 2 8 0.099 (0.010;0.506)

0.013 14 61 4 7.497 (2.698;28.985) < 10-4 aOdds ratio (OR) describes the strength of the association between Selinexor concentration a pherotype and a particular serotype. In each case, if the OR is significantly > 1, CSP-1 is associated with the serotype and if OR is significantly < 1 means that

the serotype is enriched in CSP-2 beyond what would be expected. bValues obtained after false-discovery rate correction for multiple testing MLST is a Dactolisib cost sequence based approach that uses the sequence of internal fragments of housekeeping genes for the purpose of characterizing, typing, and classifying members of bacterial populations. The data derived from MLST can also be used to study the population genetics of bacteria such as Streptococcus pneumoniae [28]. Applying eBURST to MLST data originates subnetworks of isolates with increased probability of sharing a recent common

ancestor. These subnetworks define clonal complexes as groups of isolates that share the alleles at no less than six loci with at least another member of that group [29]. MLST from 90 selected strains [30] revealed 57 different sequence types grouped into 39 distinct clonal complexes. The ability of sequence type and clonal complex to predict the pherotype is remarkably high, both with W > 0.97 (Table 1). PFGE and MLST are widely used tools to define bacterial clones, the fact that the groups defined by both these methods show such strong correspondence with pherotype further strengthen the indication that pherotype is Anidulafungin (LY303366) a clonal property within the pneumococcal population. A consistent hypothesis with pherotype clonality is that the role of CSP in triggering competence and its consequences on lateral gene transfer is itself responsible for the distribution of the pherotypes in the pneumococcal population. If this hypothesis is correct and the pherotype is indeed restricting gene transfer within the pneumococcal population, genes that are under recent strong selective pressure and that are known to be horizontally transferred should be associated with pherotype. Pherotype and antibiotic resistance To test our hypothesis, we checked if there was an association between antibiotic resistance and pherotype.