Molecular switch key to bacterial dysentery

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Bacteria of the genus Shigella, closely related to the well-known Escherichia coli, are the second most common cause of fatal bacterial diarrheal diseases, with over 200,000 victims worldwide every year. There are repeated outbreaks of strains that are resistant to common antibiotics. A molecular switch has been found to be responsible for the bacteria’s ability to cause disease. The switch, called VirF, is a protein that controls the expression of genes that are necessary for the bacteria to invade and multiply in host cells.

Molecular Switch Plays a Pivotal Role in Bacterial Dysentery: A Deeper Understanding

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Unveiling the Mechanism Behind Shigella’s Infectious Capacity

Shigella, a bacterium closely related to the familiar Escherichia coli, is the second leading cause of fatal bacterial diarrheal diseases worldwide. With over 200,000 victims annually, the emergence of strains resistant to common antibiotics poses a serious threat. In the pursuit of effective treatments, researchers are exploring new therapeutic targets. A team of scientists from the Max Planck Institute for Terrestrial Microbiology has shed light on a molecular switch that regulates gene distribution during cell division, revealing its crucial role in bacterial gene regulation.

A Novel Molecular Switch: The Key to Bacterial Gene Regulation

A few years ago, researchers discovered a unique molecular switch whose activation and deactivation depend on CTP, a fundamental building block of RNA. This switch is found in many bacterial proteins, suggesting a widespread control principle. The researchers’ findings indicate that this principle extends to bacterial processes relevant to humans.

Unraveling the Mystery of Bacterial Dysentery Virulence Gene Regulation

In the case of Shigella flexneri, the bacterium responsible for dysentery, the regulation of virulence genes is mediated by a CTP-dependent switch. Shigella’s ability to infect and resist antibiotics stems from plasmids, circular DNA molecules inherited independently of the genome. A protein called VirB, a transcription factor, controls the expression of gene clusters on the Shigella virulence plasmid, enabling the bacterium to infect human intestinal cells.

The Intriguing Mechanism of VirB: A Ring-Like Structure

VirB, unlike classical transcription factors, belongs to the same class of proteins as the CTP-dependent switches involved in distributing genetic information during cell division. Sara Jakob, the study’s lead author, explains the intriguing mechanism: VirB binds to DNA at a site distant from its target genes, encircling the DNA molecule in a ring-like structure. CTP acts like double-sided tape, holding the VirB ring closed. In this form, VirB slides along the DNA, exposing the binding site and allowing more VirB molecules to attach. These molecules modify the DNA structure, enabling the expression of target genes.

CTP-Dependent Switch: A Potential Therapeutic Target for Dysentery

The CTP-dependent switch mechanism allows VirB to act as a molecular switch, remotely controlling gene expression during bacterial pathogenesis. Mutations that disrupt CTP binding inhibit VirB loading onto DNA and suppress the formation of VirB-DNA complexes and virulence gene expression in Shigella cells.

Martin Thanbichler, the study’s senior author, emphasizes the significance of this discovery: “VirB could be a target for novel therapeutics that specifically suppress Shigella virulence, leading to improved treatment of shigellosis.” He further adds, “Our work provides the first evidence for a CTP-dependent switch involved in gene regulation, highlighting the far-reaching importance of this newly discovered regulatory principle in controlling biological processes in bacteria.”

Wrapping Up: A Deeper Understanding for Better Treatment of Dysentery

The identification of the CTP-dependent switch mechanism in bacterial gene regulation opens up new avenues for combating Shigella and related bacterial pathogens. This discovery not only contributes to a better understanding of bacterial infectious capacity but also paves the way for the development of novel therapeutic strategies to combat dysentery and other bacterial diseases..

FAQ’s

1. What is the significance of the CTP-dependent switch in bacterial gene regulation?

The CTP-dependent switch plays a crucial role in regulating gene expression in bacteria, including Shigella flexneri, the bacterium responsible for dysentery. This switch controls the expression of virulence genes, enabling the bacterium to infect human intestinal cells and resist antibiotics.

2. How does the CTP-dependent switch function in Shigella flexneri?

In Shigella flexneri, the CTP-dependent switch controls the expression of virulence genes located on the Shigella virulence plasmid. A protein called VirB, a transcription factor, binds to DNA at a site distant from its target genes and forms a ring-like structure. CTP acts like double-sided tape, holding the VirB ring closed. In this form, VirB slides along the DNA, exposing the binding site and allowing more VirB molecules to attach. These molecules modify the DNA structure, enabling the expression of target genes.

3. Why is targeting the CTP-dependent switch a potential therapeutic strategy?

Targeting the CTP-dependent switch could lead to the development of novel therapeutics that specifically suppress Shigella virulence. Mutations that disrupt CTP binding inhibit VirB loading onto DNA and suppress the formation of VirB-DNA complexes and virulence gene expression in Shigella cells. By targeting the CTP-dependent switch, it may be possible to inhibit the expression of virulence genes and reduce the pathogenicity of Shigella.

4. What are the implications of this discovery for understanding bacterial infectious capacity?

The discovery of the CTP-dependent switch mechanism in bacterial gene regulation provides a deeper understanding of how bacteria regulate virulence gene expression. This knowledge can help researchers identify novel therapeutic targets and develop more effective treatments for bacterial infections.

5. How does this research contribute to the development of novel therapeutic strategies?

This research opens up new avenues for combating Shigella and related bacterial pathogens. By understanding the mechanism of the CTP-dependent switch, researchers can design drugs that specifically target this switch and inhibit the expression of virulence genes. This could lead to the development of more effective and targeted therapies for dysentery and other bacterial diseases.

Links to additional Resources:

https://www.nature.com https://www.science.org https://www.cell.com.