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In laboratory cultures, one target of StkP is the phosphoglucosamine mutase GlmM involved in the first steps of peptidoglycan biosynthesis. In order to further elucidate the importance of StkP in<jats:italic>S. pneumoniae<\/jats:italic>, its role in resistance to \u03b2-lactams has been assessed by mutational analysis in laboratory cultures and its genetic conservation has been investigated in isolates from infected sites (virulent), asymptomatic carriers, susceptible and non-susceptible to \u03b2-lactams.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Deletion replacement mutation in<jats:italic>stkP<\/jats:italic>conferred hypersensitivity to penicillin G and was epistatic on mutations in PBP2X, PBP2B and PBP1A from the resistant 9V clinical isolate URA1258. Genetic analysis of 55 clinical isolates identified 11 StkP alleles differing from the reference R6 allele. None relevant mutation in the kinase or the PASTA domains were found to account for susceptibility of the isolates. Rather the minimal inhibitory concentration (MIC) values of the strains appeared to be determined by their PBP alleles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The results of genetic dissection analysis in lab strain Cp1015 reveal that StkP is involved in the bacterial response to penicillin and is epistatic on mutations PBP 2B, 2X and 1A. However analysis of the clinical isolates did not allow us to find the StkP alleles putatively involved in determining the virulence or the resistance level of a given strain, suggesting a strong conservation of StkP in clinical isolates.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1471-2180-9-121","type":"journal-article","created":{"date-parts":[[2009,6,6]],"date-time":"2009-06-06T00:50:48Z","timestamp":1244249448000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["The highly conserved serine threonine kinase StkP of Streptococcus pneumoniae contributes to penicillin susceptibility independently from genes encoding penicillin-binding proteins"],"prefix":"10.1186","volume":"9","author":[{"given":"Ricardo","family":"Dias","sequence":"first","affiliation":[]},{"given":"David","family":"F\u00e9lix","sequence":"additional","affiliation":[]},{"given":"Manuela","family":"Cani\u00e7a","sequence":"additional","affiliation":[]},{"given":"Marie-Claude","family":"Trombe","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2009,6,5]]},"reference":[{"key":"792_CR1","doi-asserted-by":"publisher","first-page":"4891","DOI":"10.1073\/pnas.080067697","volume":"97","author":"SR Filipe","year":"2000","unstructured":"Filipe SR, Tomasz A: Inhibition of the expression of penicillin resistance in Streptococcus pneumoniae by inactivation of cell wall muropeptide branching genes. 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