Methicillin treatment reveals that FtsZ phosphorylation influences the cell division of Streptococcus pneumoniae
Artikel i vetenskaplig tidskrift, 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

Författare

Sathya Narayanan Nagarajan

Molecular Microbiology and Structural Biochemistry

Sylvie Manuse

Molecular Microbiology and Structural Biochemistry

Dimitri Juillot

Université Paris-Saclay

L. Claude

Molecular Microbiology and Structural Biochemistry

Vaishnavi Ravikumar

Chalmers, Life sciences, Systembiologi

Universität Tübingen

Emmanuelle Neumann

Université Grenoble Alpes

Jean Pierre Lavergne

Molecular Microbiology and Structural Biochemistry

M. Franz-Wachtel

Universität Tübingen

B. Macek

Universität Tübingen

Ivan Mijakovic

Chalmers, Life sciences, Systembiologi

Cecile Morlot

Université Grenoble Alpes

Rut Carballido-Lopez

Université Paris-Saclay

C. Grangeasse

Molecular Microbiology and Structural Biochemistry

PNAS Nexus

27526542 (eISSN)

Vol. 5 6 pgag200

Är Bacillus subtilis PtkA reglerad som ett "cyclin-dependant" kinas?

Vetenskapsrådet (VR) (2020-03176), 2021-01-01 -- 2024-12-31.

Ämneskategorier (SSIF 2025)

Molekylärbiologi

Cell- och molekylärbiologi

Mikrobiologi inom det medicinska området

DOI

10.1093/pnasnexus/pgag200

PubMed

42311477

Mer information

Senast uppdaterat

2026-06-22