Surreal illustration of bacteria constructing a protective shield around human cells, representing potential cancer therapy breakthrough.

Brucella's Silent Shield: How a Bacterial Porin Could Unlock New Cancer Therapies

Elliot Brynn in Science & Nature August 2025 • 4 min read.

"Scientists discover Omp2b, an essential protein from Brucella melitensis, that suppresses cell death, offering potential insights into apoptosis and cancer treatment."

Apoptosis, or programmed cell death, is a crucial process that helps the body eliminate damaged or unwanted cells. However, many intracellular pathogens, including bacteria, have developed ways to inhibit apoptosis in order to survive and replicate within their host cells. Brucellae, the bacteria responsible for brucellosis, a widespread zoonotic disease, are known to prevent apoptosis in infected cells, likely to support their own survival and replication.

Identifying the mechanisms by which bacteria like Brucellae manipulate host cell apoptosis could offer significant insights into new therapeutic strategies. A recent study published in PLOS ONE has identified a key Brucella protein, Omp2b, as a potent suppressor of Bax-induced cell death. This discovery not only sheds light on bacterial pathogenesis but also offers potential avenues for developing novel cancer therapies.

The research team, led by Géraldine Laloux and Xavier De Bolle at the University of Namur, Belgium, employed a genome-wide functional screening in yeast to identify Brucella melitensis proteins that could inhibit cell death. This innovative approach led to the identification of Omp2b, an essential porin, as a suppressor of Bax-induced cell death, setting the stage for further exploration of its therapeutic potential.

Unveiling Omp2b: A Bacterial Protein with Surprising Potential

Surreal illustration of bacteria constructing a protective shield around human cells, representing potential cancer therapy breakthrough.

The study's methodology involved screening the Brucella melitensis ORFeome, a comprehensive library of the bacteria's coding sequences, to find proteins that could inhibit Bax-induced cell death in yeast. Yeast, specifically Saccharomyces cerevisiae, is a well-established model for studying apoptosis due to its simplicity and genetic tractability. The ectopic production of mammalian pro-apoptotic proteins like Bax in yeast induces cell death, providing a platform to screen for inhibitors.

The screening process identified Omp2b as a significant inhibitor of Bax-induced cell death. Unlike its close paralog Omp2a, Omp2b demonstrated a unique ability to prevent the lethal effects of Bax in yeast. Further characterization of Omp2b size variants revealed that signal peptide processing is crucial for its protective effect. This suggests that the correct processing and maturation of Omp2b are necessary for its function.

Key findings of the study include:

Omp2b effectively prevents Bax-induced cell death in yeast.
Signal peptide processing is essential for Omp2b's function.
Omp2b exhibits a distinct mechanism compared to its paralog Omp2a.
This research marks the first application of a bacterial genome-wide library in a yeast-rescue screening strategy for apoptosis regulators.

Omp2b belongs to a class of proteins known as porins, which are integral membrane proteins that form pores in the outer membranes of bacteria. These pores facilitate the transport of small molecules across the membrane, playing a vital role in bacterial survival and interaction with the environment. The discovery that Omp2b can suppress cell death adds a new dimension to our understanding of porin function and its potential implications for both bacterial pathogenesis and therapeutic interventions.

Implications and Future Directions

This research opens up exciting new avenues for exploring the potential of Omp2b as a therapeutic agent. The ability of Omp2b to suppress Bax-induced cell death suggests that it could play a role in modulating apoptosis in mammalian cells, particularly in cancer. Cancer cells often evade apoptosis, allowing them to proliferate uncontrollably. By understanding how Omp2b inhibits cell death, scientists may be able to develop new strategies to trigger apoptosis in cancer cells, leading to more effective cancer treatments.

About this Article -

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This article is based on research published under:

DOI-LINK: 10.1371/journal.pone.0013274, Alternate LINK

Title: Identification Of The Essential Brucella Melitensis Porin Omp2B As A Suppressor Of Bax-Induced Cell Death In Yeast In A Genome-Wide Screening

Subject: Multidisciplinary

Journal: PLoS ONE

Publisher: Public Library of Science (PLoS)

Authors: Géraldine Laloux, Michaël Deghelt, Marie De Barsy, Jean-Jacques Letesson, Xavier De Bolle

Published: 2010-10-11

Everything You Need To Know

What is Omp2b, and why is its ability to block cell death considered a significant discovery?

Omp2b, an essential protein from Brucella melitensis, has the remarkable ability to block cell death. This discovery is significant because it opens new pathways for understanding apoptosis and could lead to the development of innovative cancer treatments. Apoptosis is a crucial process for eliminating damaged cells, and Omp2b's ability to suppress it offers a novel approach to potentially manipulating this process in cancer therapy.

How was Omp2b identified as a suppressor of cell death, and what role did yeast play in this discovery?

Omp2b was identified through a genome-wide functional screening in yeast. Researchers screened the Brucella melitensis ORFeome to identify proteins that could inhibit Bax-induced cell death in Saccharomyces cerevisiae (yeast). Unlike Omp2a, Omp2b demonstrated a unique ability to prevent the lethal effects of Bax in yeast, showcasing the value of using bacterial genome-wide libraries in yeast-rescue screening strategies for apoptosis regulators.

What is the general function of porins, and how does Omp2b fit into this class of proteins?

Omp2b belongs to the porin class of proteins. Porins are integral membrane proteins that form pores in the outer membranes of bacteria, allowing the transport of small molecules across the membrane. Omp2b's ability to suppress cell death adds another layer to the understanding of porin function. Understanding the role of Omp2b will improve understanding of bacterial pathogenesis.

Why is the ability of Omp2b to suppress Bax-induced cell death potentially relevant in the context of cancer treatment?

The ability of Omp2b to suppress Bax-induced cell death is significant because it suggests a potential role in modulating apoptosis in mammalian cells, especially in cancer cells. Because cancer cells evade apoptosis, understanding how Omp2b inhibits cell death could lead to new strategies to trigger apoptosis in these cells. However, further research is needed to translate these findings into effective cancer treatments. Investigating Omp2b can improve current treatments.

What innovative methodology was used to identify Omp2b, and how does it expand the approaches for discovering therapeutic molecules?

The discovery of Omp2b as a suppressor of Bax-induced cell death is a novel application of a bacterial genome-wide library in a yeast-rescue screening strategy for apoptosis regulators. The use of Saccharomyces cerevisiae as a model for studying apoptosis is well-established, but leveraging a bacterial genome-wide library to identify apoptosis inhibitors represents a innovative approach. This methodology opens doors for using similar strategies to identify other molecules with therapeutic potential.