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Updated: Jun 19, 2026

Visual and Microscopic Evaluation of Streptomyces Developmental Mutants
Published on: September 12, 2018
Methicillin treatment reveals that FtsZ phosphorylation influences the cell division of Streptococcus pneumoniae
Sathya Narayanan Nagarajan1, Sylvie Manuse1, Dimitri Juillot2
1Molecular Microbiology and Structural Biochemistry, UMR 5086, Université Claude Bernard Lyon 1, CNRS, 69007 Lyon, France.
Abstract:
Protein phosphorylation plays a crucial role in regulating cell division and morphogenesis in many bacteria. In Streptococcus pneumoniae, the serine/threonine kinase StkP orchestrates cell wall assembly and cell morphogenesis by phosphorylating several proteins involved in cell division. In this study, we provide evidence that FtsZ, a conserved tubulin-like protein that coordinates pneumococcal cell elongation and constriction, is phosphorylated in vivo by StkP at six threonine residues within its C-terminal linker (CTL). Mutational analysis reveals the structural role of the CTL in pneumococcal cell division and further shows that its phosphorylation status influences cell morphogenesis. Importantly, phosphomimetic FtsZ mutants rescue division blocks induced by sublethal concentrations of methicillin, which targets the essential septal cell wall synthase PBP2x. Additionally, we demonstrate that CTL phosphorylation affects FtsZ polymerization and filament bundling in vitro. It also accelerates FtsZ treadmilling dynamics and alters its interactome in vivo. Altogether, these findings support a model in which CTL phosphorylation fine-tunes FtsZ filament dynamics to sustain cell division under β-lactam stress, representing a potential adaptive mechanism for antibiotic tolerance.
Insights
Streptococcus pneumoniae's cell division protein FtsZ is phosphorylated by StkP kinase. This phosphorylation fine-tunes FtsZ dynamics, aiding cell division under antibiotic stress and potentially enhancing antibiotic tolerance.
Area of Science:
- Bacterial cell division
- Protein phosphorylation
- Microbial morphogenesis
Background:
- Protein phosphorylation regulates bacterial cell division and morphogenesis.
- In Streptococcus pneumoniae, the kinase StkP controls cell wall assembly and morphogenesis.
- StkP phosphorylates key proteins involved in bacterial cell division.
Purpose of the Study:
- To investigate the phosphorylation of FtsZ by StkP in Streptococcus pneumoniae.
- To elucidate the role of FtsZ C-terminal linker (CTL) phosphorylation in cell division and morphogenesis.
- To understand the impact of FtsZ phosphorylation on bacterial adaptation to antibiotic stress.
Main Methods:
- In vivo and in vitro phosphorylation assays using StkP and FtsZ.
- Site-directed mutagenesis of FtsZ phosphorylation sites.
- Analysis of FtsZ polymerization, filament bundling, and treadmilling dynamics.
- Investigating FtsZ interactome and rescue of methicillin-induced division blocks.
Main Results:
- FtsZ is phosphorylated by StkP at six threonine residues in its C-terminal linker (CTL).
- FtsZ CTL phosphorylation influences pneumococcal cell morphogenesis and division.
- Phosphomimetic FtsZ mutants partially rescue division defects caused by methicillin.
- CTL phosphorylation affects FtsZ polymerization, filament bundling, and dynamics in vitro and in vivo.
Conclusions:
- FtsZ CTL phosphorylation by StkP is a critical regulatory mechanism in Streptococcus pneumoniae.
- Phosphorylation fine-tunes FtsZ filament dynamics, contributing to cell division under stress.
- This phosphorylation represents a potential adaptive mechanism for antibiotic tolerance in bacteria.
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