Bacillus subtilis MntR coordinates the transcriptional regulation of manganese uptake and efflux systems Original paper
Researched by:
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Divine Aleru
ID
Divine Aleru
Read MoreI am a biochemist with a deep curiosity for the human microbiome and how it shapes human health, and I enjoy making microbiome science more accessible through research and writing. With 2 years experience in microbiome research, I have curated microbiome studies, analyzed microbial signatures, and now focus on interventions as a Microbiome Signatures and Interventions Research Coordinator.
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Metals
Metals
Heavy metals influence microbial pathogenicity in two ways: they can be toxic to microbes by disrupting cellular functions and inducing oxidative stress, and they can be exploited by pathogens to enhance survival, resist treatment, and evade immunity. Understanding metal–microbe interactions supports better antimicrobial and public health strategies.
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Divine Aleru
Read More
Researched by:
-
Divine Aleru
ID
Divine Aleru
Read More
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Divine Aleru
What was studied?
This study investigated the role of the MntR metalloregulator in coordinating manganese (Mn) homeostasis in Bacillus subtilis. It explored how MntR controls the transcription of genes involved in Mn uptake and efflux systems, focusing on MntH, MntABCD (for Mn import), and MneP, MneS (for Mn efflux). The study further delved into how MntR regulates these systems in response to varying Mn(II) levels and its crucial role in preventing Mn(II) toxicity.
Who was studied?
The study primarily focused on Bacillus subtilis, using both wild-type and mutant strains. The mutants involved included those lacking MntR, MneP, and MneS, allowing the researchers to examine the impact of these transporters on Mn(II) sensitivity and regulation. The study also utilized DNA-binding and transcription assays to investigate how MntR activates and represses the expression of relevant genes.
What were the most important findings?
The study identified MntR as the central regulator that directly activates Mn(II) efflux genes (mneP and mneS) while repressing Mn(II) import genes (mntH and mntA) under conditions of Mn sufficiency. Mutants lacking MntR or the Mn(II) efflux pumps (MneP and MneS) were highly sensitive to Mn(II), accumulating excessive Mn(II) intracellularly. The research showed that MntR directly binds to the regulatory regions of both the uptake and efflux genes, with different affinities depending on the metal’s concentration. The study also revealed that the efflux systems are induced at higher Mn(II) concentrations than the uptake systems, highlighting a delicate balance between Mn(II) import and export. Notably, the MntR-regulated Mn(II) efflux systems (MneP and MneS) played a significant role in preventing Mn(II) toxicity, as seen in the pronounced sensitivity of double mutants lacking both pumps.
What are the greatest implications of this study?
This study enhances the understanding of how bacteria like Bacillus subtilis maintain Mn(II) homeostasis, crucial for both growth and survival under varying metal conditions. It underscores the importance of the MntR-regulated Mn(II) efflux systems in defending against Mn(II) toxicity, which is essential for bacterial pathogenesis and stress resistance. These insights can inform future strategies for targeting metal homeostasis in pathogenic bacteria, offering potential therapeutic approaches for combating metal-related toxicity in infections. Additionally, the study provides a model for understanding how bacteria manage metal ion homeostasis, which could have broader implications in microbiome research and antimicrobial development.
Manganese (Mn)
Manganese plays a pivotal role in microbial pathogenesis. As a vital cofactor for enzymes involved in antioxidant defense and metabolism, manganese is essential for pathogens, enabling them to survive within the host. However, when not properly managed, manganese can become toxic to both the host and the pathogen. The host’s immune system, through mechanisms like the secretion of calprotectin, tries to limit microbial access to manganese, creating an ongoing battle between host defenses and microbial survival .