ArticleMolecular microbiology2012
Analysis of the role of Bacillus subtilis σ(M) in β-lactam resistance reveals an essential role for c-di-AMP in peptidoglycan homeostasis.
Article in Molecular microbiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 164 papers.
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164 citing papers in PubMed, 244 citations in OpenAlex.
- The phenotypic landscape of the model firmicuteProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Mislocalization of PBPs inMicrobiology spectrum · 2026Article
- Cyclic di-AMP signaling and regulation inmSphere · 2026Review
- ClpC1-dependent iron homeostasis underlies mycobacterial defense against oxygen-driven Fenton reaction during reactivation.Microbiology spectrum · 2026Article
- A c-di-AMP-controlled glutamine synthesis pathway promotes persistence ofbioRxiv : the preprint server for biology · 2026Article
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- Deciphering the metabolic details of L-lysine toxicity in cyanobacteria.Plant physiology · 2026Article
- Post-translational modifications of GlmR integrate metabolic and stress signals to maintain cell envelope homeostasis in Bacillus subtilis.PLoS genetics · 2026Article
- Persistent Gaps in the Ultimate Mechanisms of Antimicrobial-Induced Bacterial Killing.Antibiotics (Basel, Switzerland) · 2026Review
- Staying in the loop to make ends meet: roles and regulation of GlmR inbioRxiv : the preprint server for biology · 2025Article
- Cyclic Di-AMP Affects Cell Membrane Integrity of Streptococcus pneumoniae.Molecular microbiology · 2025Article
- A widespread family of viral sponge proteins reveals specific inhibition of nucleotide signals in anti-phage defense.Molecular cell · 2025Article
- Cyclic-di-AMP modulates cellular turgor in response to defects in bacterial cell wall synthesis.Nature microbiology · 2025Article
- Formation of Mono-Organismal and MixedMicroorganisms · 2025Article
- Review
- A mutation in RNA polymerase imparts resistance to β-lactams by preventing dysregulation of amino acid and nucleotide metabolism.Cell reports · 2025Article
- Membrane-embedded CdaA is required for efficient synthesis of second messenger cyclic di-AMP.Communications biology · 2024Article
- Cyclic di-AMP regulates genome stability and drug resistance inPNAS nexus · 2024Article
- Characterization of c-di-AMP signaling in the periodontal pathobiont, Treponema denticola.Molecular oral microbiology · 2024Article
104 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The Bacillus subtilis extracytoplasmic function (ECF) σ factor σ(M) is inducible by, and confers resistance to, several cell envelope-acting antibiotics. Here, we demonstrate that σ(M) is responsible for intrinsic β-lactam resistance, with σ(X) playing a secondary role. Activation of σ(M) upregulates several cell wall biosynthetic enzymes including one, PBP1, shown here to be a target for the beta-lactam cefuroxime. However, σ(M) still plays a major role in cefuroxime resistance even in cells lacking PBP1. To better define the role of σ(M) in β-lactam resistance, we characterized suppressor mutations that restore cefuroxime resistance to a sigM null mutant. The most frequent suppressors inactivated gdpP (yybT) which encodes a cyclic-di-AMP phosphodiesterase (PDE). Intriguingly, σ(M) is a known activator of disA encoding one of three paralogous diadenylate cyclases (DAC). Overproduction of the GdpP PDE greatly sensitized cells to β-lactam antibiotics. Conversely, genetic studies indicate that at least one DAC is required for growth with depletion leading to cell lysis. These findings support a model in which c-di-AMP is an essential signal molecule required for cell wall homeostasis. Other suppressors highlight the roles of ECF σ factors in counteracting the deleterious effects of autolysins and reactive oxygen species in β-lactam-treated cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.