Related Experiment Video

Updated: Nov 11, 2025

A Fast and Reliable Pipeline for Bacterial Transcriptome Analysis Case study: Serine-dependent Gene Regulation in Streptococcus pneumoniae
10:18

A Fast and Reliable Pipeline for Bacterial Transcriptome Analysis Case study: Serine-dependent Gene Regulation in Streptococcus pneumoniae

Published on: April 25, 2015

10.6K

A molecular link between cell wall biosynthesis, translation fidelity, and stringent response in Streptococcus

Surya D Aggarwal1, Adrian J Lloyd2, Saigopalakrishna S Yerneni3

  • 1Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213.

Proceedings of the National Academy of Sciences of the United States of America
|March 31, 2021
PubMed

Insights

Streptococcus pneumoniae's MurM protein prevents toxic translation errors during stress by incorporating mischarged seryl-tRNAAla. Deletion of MurMN causes growth arrest and lysis, highlighting MurMN's role in bacterial stress response and host interactions.

Area of Science:

  • Microbiology
  • Bacterial Pathogenesis
  • Molecular Biology

Background:

  • Bacterial survival hinges on responding to environmental stressors.
  • Streptococcus pneumoniae relies on cell wall biosynthesis proteins MurM and MurN for branched muropeptide production.
  • Acidic stress impacts tRNA synthetase fidelity, leading to toxic mischarging.

Purpose of the Study:

  • To investigate the role of MurM and MurN in Streptococcus pneumoniae's response to acidic stress.
  • To elucidate the mechanism by which MurMN influences bacterial growth, lysis, and host-pathogen interactions.
  • To explore the link between mischarged tRNAs, stringent response, and MurM function.

Main Methods:

  • Comparative growth analysis of wild-type and ΔmurMN strains under acidic conditions.
  • Assessment of alanyl-tRNAAla synthetase efficiency and tRNA misacylation.
  • Genetic manipulation including gene deletion and overexpression.
  • Investigation of LytA's role in lysis and macrophage phagocytosis.

Main Results:

  • Wild-type S. pneumoniae thrives in mild acidic stress, while ΔmurMN exhibits growth arrest and lysis.
  • Acidic stress reduces alanyl-tRNAAla synthetase fidelity, increasing toxic seryl-tRNAAla mischarging.
  • MurM specifically incorporates seryl groups from mischarged tRNAAla into cell wall precursors.
  • Inhibition of stringent response or overexpression of tRNA synthetase editing domain rescues growth defects.
  • Enhanced lysis in ΔmurMN is LytA-dependent, impacting macrophage phagocytosis.

Conclusions:

  • MurM contributes to translational fidelity and stress response modulation by reducing mischarged tRNAs.
  • Mischarged tRNA accumulation triggers the stringent response, halting translation to prevent protein misfolding.
  • MurMN attenuates stress responses, influencing host-pathogen interactions.
  • MurM acts as a first line of defense against translation errors, with MurMN deletion leading to severe stress responses.
Keywords:
Streptococcus pneumoniaeautolysiscell wallstringent responsetranslation quality control

More Related Videos

A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues07:10

A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues

Published on: February 19, 2019

9.2K
Synthesis of Masarimycin, a Small Molecule Inhibitor of Gram-Positive Bacterial Growth09:10

Synthesis of Masarimycin, a Small Molecule Inhibitor of Gram-Positive Bacterial Growth

Published on: January 7, 2022

2.6K

Related Concept Videos

Stringent Response in E. coli01:23

Stringent Response in E. coli

Bacterial growth is closely tied to nutrient availability, with cells proliferating exponentially under favorable conditions and entering a stationary phase when resources become scarce. This transition is mediated by a regulatory mechanism known as the stringent response, which allows bacteria to adapt to nutrient deprivation by modulating gene expression and metabolic activity.During nutrient scarcity, intracellular amino acid levels decline. It results in the accumulation of uncharged tRNAs...
124
Coordination of Gene Expression Processes in Bacteria01:29

Coordination of Gene Expression Processes in Bacteria

The DNA replication, transcription, and translation processes are intricately coupled in bacteria, allowing efficient gene expression and rapid protein synthesis. While this physical and functional coordination is advantageous, it introduces challenges that bacteria overcome through specific regulatory mechanisms.Coupling of Replication, Transcription, and TranslationThe coupling of replication, transcription, and translation is a hallmark of bacterial gene expression. As the replisome unwinds...
332
Bacterial Cell Wall01:22

Bacterial Cell Wall

The bacterial cell wall is an essential structural component that encases the plasma membrane, preserving cellular integrity, determining shape, and protecting against osmotic stress. This rigid yet flexible structure primarily comprises peptidoglycan, a polymer that forms a mesh-like matrix conferring mechanical strength and flexibility.Peptidoglycan Composition and StructurePeptidoglycan, the core of the bacterial cell wall, comprises alternating units of N-acetylglucosamine (NAG) and...
1.4K
Peptidoglycan Synthesis01:28

Peptidoglycan Synthesis

Structure of PeptidoglycanPeptidoglycan is a vital structural component of the bacterial cell wall, providing mechanical strength and shape to the cell. It consists of repeating units of two sugars—N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM)—linked by β-1,4 glycosidic bonds. These sugar chains are cross-linked by short peptide chains, forming a mesh-like polymer that surrounds the bacterial plasma membrane.Cytoplasmic Phase – Precursor SynthesisPeptidoglycan...
1.1K
Formation of Lipopolysaccharides01:19

Formation of Lipopolysaccharides

Lipopolysaccharides (LPS) are crucial components of the outer membrane of Gram-negative bacteria, serving both structural and functional roles. It contributes to membrane stability and protects bacteria from host immune responses. LPS is composed of three major regions—lipid A, a core oligosaccharide, and an O antigen. The biosynthesis and assembly of LPS involve a highly coordinated set of enzymatic reactions and transport mechanisms. Additionally, LPS is recognized as an endotoxin,...
232
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...
3.8K