Details

Autor(en) / Beteiligte

• Huang, Yan-Ying
• Sun, Yan-Hong
• Huang, Nan
• Liu, Xiao-Xiang
• Yan, Jie
• Sun, Ai-Hua

Titel

Sublethal β-lactam antibiotics induce PhpP phosphatase expression and StkP kinase phosphorylation in PBP-independent β-lactam antibiotic resistance of Streptococcus pneumoniae

Ist Teil von

• Biochemical and biophysical research communications, 2018-09, Vol.503 (3), p.2000-2008

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• StkP and PhpP of Streptococcus pneumoniae have been confirmed to compose a signaling couple, in which the former is a serine/threonine (Ser/Thr) kinase while the latter was annotated as a phosphotase. StkP has been reported to be involved in penicillin-binding protein (PBP)-independent penicillin resistance of S. pneumoniae. However, the enzymatic characterization of PhpP and the role of PhpP in StkP-PhpP couple remain poorly understood. Here we showed that 1/4 minimal inhibitory concentration (MIC) of penicillin (PCN) or cefotaxime (CTX), the representatives of β-lactam antibiotics, could induce the expression of stkP and phpP genes and phosphorylation of StkP in PCN/CTX-sensitive strain ATCC6306 and three isolates of S. pneumoniae (MICs: 0.02–0.5 μg/ml). The product of phpP gene hydrolyzed PP2C type Ser/Thr phosphotase-specific RRA (pT)VA phosphopeptide substrate with the Km and Kcat values of 277.35 μmoL/L and 0.71 S-1, and the hydrolytic activity was blocked by sodium fluoride, a PP2C type Ser/Thr phosphatase inhibitor. The phosphorylation levels of StkP in the four phpP gene-knockout (ΔphpP) mutants were significantly higher than that in the wild-type strains. In particular, the MICs of PCN and CTX against the ΔphpP mutants were significantly elevated as 4–16 μg/ml. Therefore, our findings confirmed that sublethal PCN and CTX act as environmental inducers to cause the increase of phpP and stkP gene expression and StkP phosphorylation. PhpP is a PP2C type Ser/Thr protein phosphatase responsible for dephosphorylation of StkP. Knockout of the phpP gene results in a high level of StkP phosphorylation and PBP-independent PCN/CTX resistance of S. pneumoniae. •Study a signaling couple of StkP and PhpP of Streptococcus pneumoniae.•Contrast to the phosphorylation levels of ΔphpP and wild-type strains.•Demonstrate PCN and CTX can as environmental factors.