Methicillin treatment reveals that FtsZ phosphorylation influences the cell division of Streptococcus pneumoniae
Journal article, 2026
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.
FtsZ
cell division
protein phosphorylation
peptidoglycan
Streptococcus pneumoniae
Author
Sathya Narayanan Nagarajan
Microbiologie moléculaire et iochimie structurale
Sylvie Manuse
Microbiologie moléculaire et iochimie structurale
Dimitri Juillot
University Paris-Saclay
L. Claude
Microbiologie moléculaire et iochimie structurale
Vaishnavi Ravikumar
Chalmers, Life Sciences, Systems and Synthetic Biology
University of Tübingen
Emmanuelle Neumann
Grenoble Alpes University
Jean Pierre Lavergne
Microbiologie moléculaire et iochimie structurale
M. Franz-Wachtel
University of Tübingen
B. Macek
University of Tübingen
Ivan Mijakovic
Chalmers, Life Sciences, Systems and Synthetic Biology
Cecile Morlot
Grenoble Alpes University
Rut Carballido-Lopez
University Paris-Saclay
C. Grangeasse
Microbiologie moléculaire et iochimie structurale
PNAS Nexus
27526542 (eISSN)
Vol. 5 6 pgag200Is Bacillus subtilis PtkA regulated like a cyclin-dependent kinase?
Swedish Research Council (VR) (2020-03176), 2021-01-01 -- 2024-12-31.
Subject Categories (SSIF 2025)
Molecular Biology
Cell and Molecular Biology
Microbiology in the Medical Area
DOI
10.1093/pnasnexus/pgag200
PubMed
42311477