However, the results obtained from the analysis of clinical strains, seem to oppose the idea of an association of StkP with virulence [31], and with penicillin IWR-1 molecular weight susceptibility found in the model system in this work. This suggests that StkP may play an important role in the homeostasis of pneumococcus in man, regardless of both virulence and penicillin susceptibility, suggesting that none of the characteristics

play a central role on StkP. In fact, it has been suggested that StkP Milciclib supplier is a global regulator of gene expression [32]. The work by Gienfing et al., described the conservation of StkP among clinical strains and also observed the impact of stkP mutation on penicillin susceptibility on a susceptible genetic background [33]. However the association between PBPs and StkP mutation were not assessed. Here, we showed that the role of StkP on penicillin susceptibility is not related to the major genetic determinants for penicillin susceptibility in pneumococci among a set of clinical

and reference strains as well as in the set of penicillin resistant mutants. A contribution of the StkP towards penicillin susceptibility, notably attributed to its PASTA domains, has already been proposed elsewhere [34], but there was previously no supporting experimental evidence. This role for StkP is consistent with previous observations showing that Pifithrin-�� in vivo the phosphoglucomutase GlmM is involved in the first steps of peptidoglycan biosynthesis is a target for StkP [6]. Consistent with this notion, GlmM in E. coli is activated by phosphorylation [4] and in S. aureus functional GlmM is needed for full expression of methicillin resistance [35]. Although StkP is not

essential and loss of function mutations can be obtained in laboratory conditions ([6, 31] and this work), it is strongly conserved in clinical isolates, reminiscent of housekeeping genes [36]; presumably, it has an important role in natural niches. Extensive sequence analysis of StkP in susceptible and resistant pneumococcal isolates did not reveal any mutation significantly associated with susceptibility to penicillin. This suggests that stkP Dapagliflozin is of great importance for the cellular homeostatic mechanisms of S. pneumoniae and is not subject to the selective pressures caused by the β-lactams, unlike pbp genes presenting mosaic structures. PASTA domains in prokaryotic serine-threonine kinases and PBP2X are involved in cell wall motif recognition [7]. Consistent with our study, Jones and Dyson reported that the PASTA domain of STK from several species showed high amino acid sequence divergence and Ka/Ks values, suggesting that PASTA domain interact with a wider range of stem-peptide ligands [7]. We report similar observations for invasive and colonizing strains. It is thus unlikely that mutation in the kinase or the PASTA domains contributes to the characteristics of the virulent strains in our collection.