Bacterial manganese sensing and homeostasis Original paper

What was reviewed?

This review focuses on the bacterial manganese (Mn) sensing and homeostasis systems, examining the mechanisms through which bacteria regulate intracellular Mn levels. It highlights the roles of various Mn-binding regulators, including MntR and the yybP-ykoY riboswitch, as well as newly identified Mn exporters. The review also covers advances in understanding the speciation of intracellular Mn pools, the molecular mechanisms behind Mn toxicity, and the emerging families of Mn exporters.

Who was reviewed?

The review synthesized research on bacterial Mn homeostasis, covering a wide range of bacteria, including Escherichia coli, Streptococcus pneumoniae, and Bacillus subtilis, as well as other species with diverse ecological niches. The studies reviewed focused on the identification of Mn transporters, their regulation, and the effects of Mn perturbations on bacterial growth and survival.

What were the most important findings?

The review identifies key mechanisms that bacteria use to control intracellular Mn levels, primarily through Mn importers and exporters. MntR, a transcription factor, plays a central role in regulating Mn homeostasis by controlling the expression of Mn transporters like MntH and MntP. The yybP-ykoY riboswitch, a recently discovered RNA-based regulator, also plays a crucial role in the post-transcriptional regulation of Mn exporters. New families of Mn exporters, such as MntP and MneA, were highlighted for their roles in reducing intracellular Mn levels and protecting bacteria from Mn toxicity. The review also emphasizes the complex interplay between Mn and other metals, such as Fe and Zn, which can affect Mn homeostasis. Furthermore, the research underscores the importance of balancing Mn levels, as both Mn deficiency and excess can lead to bacterial dysfunction, including oxidative stress and impaired virulence. The review also highlights advances in quantifying intracellular Mn pools, with the use of techniques like EPR spectroscopy to measure the distribution of Mn in bacterial cells.

What are the greatest implications of this review?

The findings of this review have important implications for understanding bacterial metal homeostasis, especially in the context of infection. The ability of bacteria to regulate Mn levels is crucial for their survival in the host, as excessive Mn can disrupt cellular functions, while Mn limitation can impair pathogen defense mechanisms. This review suggests that targeting Mn transporters, regulators, and the riboswitch could be a promising strategy for developing new antimicrobial therapies, particularly for pathogens that rely on precise metal homeostasis for virulence. Additionally, the insights into Mn and metal interactions could help in the development of interventions that manipulate metal availability to either limit pathogen growth or promote the growth of beneficial bacteria.