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.

PNAS Nexus
|June 18, 2026
PubMed

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.

Related Concept Videos

Inhibitors of Bacterial Protein Synthesis01:25

Inhibitors of Bacterial Protein Synthesis

Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...
Inhibitors of Gram-positive Cell Wall Synthesis01:23

Inhibitors of Gram-positive Cell Wall Synthesis

Bacterial cell walls are typically rigid structures composed mainly of peptidoglycan, a mesh-like polymer that provides mechanical strength and maintains cell shape. The synthesis of peptidoglycan is a crucial process in bacterial growth and serves as a primary target for many antibiotics.Mechanism of Action of Beta-Lactam AntibioticsBeta-lactam antibiotics, such as penicillin, inhibit peptidoglycan synthesis in actively growing cells. These antibiotics share a characteristic four-membered...
Mechanism of Antibiotic Resistance in MRSA01:25

Mechanism of Antibiotic Resistance in MRSA

Antibiotic resistance in bacteria arises when microorganisms evolve the ability to withstand drugs designed to kill them or inhibit their growth, rendering once-effective treatments useless. This phenomenon, driven by genetic change and selection under antibiotic exposure, poses a profound threat to modern medicine. Mechanisms include drug-inactivating enzymes (e.g., β-lactamases), efflux pumps that eject antibiotics, mutations altering antibiotic targets, decreased drug uptake, and acquisition...
Cytoskeletal Proteins in Bacteria01:29

Cytoskeletal Proteins in Bacteria

Bacterial cells were initially considered simple, randomly organized structures lacking a cytoskeleton. However, the discovery of cytoskeleton homologs in bacteria led to the change of this opinion. Bacterial cytoskeletal filaments regulate the cell shape, cell polarity, cell division, and partitioning of plasmids during cell division. It was later discovered that bacterial cytoskeletal proteins, mainly actin and tubulin homologs, are diverse compared to their eukaryotic counterparts. On the...
Clinical Significance of Antibiotic Resistance01:25

Clinical Significance of Antibiotic Resistance

Methicillin-resistant Staphylococcus aureus (MRSA) presents a critical public health threat, arising from its capacity to resist β-lactam antibiotics due to acquisition of the mecA gene within the staphylococcal cassette chromosome mec (SCCmec). This gene encodes penicillin-binding protein 2a (PBP2a), which impairs binding efficacy of methicillin and other β-lactams. MRSA has evolved into distinct clonal lineages impacting humans and animals alike, reinforcing its significance within the One...
Gene Regulation in Microbial Communities: Quorum Sensing01:28

Gene Regulation in Microbial Communities: Quorum Sensing

Quorum sensing is a mechanism of bacterial communication that enables coordinated gene expression in response to changes in population density. This facilitates collective behaviors that enhance survival, resource acquisition, and ecological adaptation. This process relies on small signaling molecules called autoinducers that accumulate as bacterial populations grow. When a critical threshold concentration of autoinducers is reached, bacterial cells collectively modify gene expression,...