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| The cholera-pathogen Vibrio cholerae (blue) forms an aggressive biofilm on the surface of immune cells (red). Video Credit: University of Basel, Biozentrum |
Scientific Frontline: Extended "At a Glance" Summary: Aggressive Biofilms in Vibrio cholerae
The Core Concept: Vibrio cholerae, the pathogen responsible for cholera, utilizes an aggressive, mesh-like biofilm on the surface of host immune cells to trigger cell death. This mechanism represents a shift from the traditional understanding of biofilms as strictly defensive structures.
Key Distinction/Mechanism: Unlike typical biofilms composed of a slimy matrix of sugars and proteins, this specific structure consists of intertwined bacterial appendages that encase macrophages. The bacteria secrete hemolysin, a toxin that creates pores in the macrophage membrane, directly resulting in cell lysis.
Major Frameworks/Components:
- Bacterial Colonization: Vibrio cholerae uses "feeler" appendages to anchor onto the surface of macrophages.
- Extracellular Meshwork: Bacteria divide and entwine these feelers to create a lethal cage around the immune cell.
- Hemolysin Activity: This specific toxin is the primary agent identified in breaching the macrophage's protective membrane.
- Human Intestinal Organoid Model: Used to replicate the infection environment, proving that the pathogen forms these lethal biofilms after disrupting the intestinal barrier.
Branch of Science: Microbiology, Immunology, and Cell Biology.
Future Application: The identification of this aggressive strategy provides a new target for drug development. Researchers aim to determine if other pathogens utilize similar biofilm-mediated attacks, potentially leading to new classes of antibiotics or therapeutic interventions against antibiotic-resistant bacteria.
Why It Matters: This discovery reveals a sophisticated offensive strategy in a major human pathogen, challenging long-held assumptions about biofilm function. It shifts the paradigm of host-pathogen interactions and opens critical avenues for combatting infectious diseases.
Bacteria harness the power of communities. A research group at the University of Basel has now discovered that the bacterial pathogen that causes cholera forms a novel type of bacterial community on immune cells: an aggressive biofilm that is lethal for the cells. The study, recently published in the journal Cell, provides new insights into the infection strategies of pathogens.
Many bacteria adopt a fascinating defense strategy by forming communities on surfaces, known as biofilms. We encounter such biofilms in our daily lives, for example, as dental plaque in the mouth, slimy films on stones in water or even as part of our intestinal flora. Bacterial biofilms are intrinsically tolerant to antibiotics and can pose a significant threat in clinical settings when they colonize implants, catheters, or surgical instruments. This colonization enables pathogens to infiltrate our body and trigger infections that are difficult to combat by the immune system and with antibiotics.
Previously, it was assumed that bacteria form biofilms to defend and protect themselves. The research team led by Professor Knut Drescher at the Biozentrum, University of Basel, has now demonstrated, in their recently published “Cell” study, that bacteria form biofilms on the surface of immune cells. This previously unknown type of community differs from already known bacterial biofilms not only in its structure, but also in its function: instead of serving a protective purpose, this biofilm is an aggressive trait.
Meshwork rather than typical slimy matrix
Drescher’s team has discovered this novel type of biofilm in the cholera-causing pathogen Vibrio cholerae. This bacterium colonizes various immune cells in the human host.
To better understand biofilm formation on immune cells, the researchers focused on a certain type of phagocytic cells, so-called macrophages. “Bacteria that accidently encounter a macrophage attach to the cell’s surface using a kind of a ‘feeler’,” explains first author Dr. Lucia Vidakovic. “Subsequently, the bacteria start to divide and intertwine their feeler-like appendages.” The structure of the extracellular matrix of this type of biofilm is thus fundamentally different from previously known ones, in which bacteria are typically embedded within a slimy matrix consisting of sugars and proteins.
Biofilms on immune cells: aggression instead of defense
Over time, the biofilms produced by the cholera pathogen completely encase macrophages, leading to cell death. “The bacterial community actively attacks and kills the immune cells. However, we initially didn’t understand the exact mechanism,” says Vidakovic. “To solve this puzzle, we meticulously investigated all 14 known toxins produced by the cholera pathogen and could finally identify the hemolysin as the culprit.” This toxin forms pores in the protective membrane of the immune cells, thus killing them.
Cholera is a life-threatening infectious disease that causes severe diarrhea. As humans are the only host of the cholera-pathogen, the scientists established a human intestinal organoid model. Using this model, they could demonstrate that Vibrio cholerae is able to form lethal biofilms on macrophages after colonizing and disrupting the human intestinal barrier.
“This novel strategy of attack, employed by the bacteria, can significantly affect the progression of the cholera infection,” adds Knut Drescher. "In the next step, we aim to explore whether other pathogens also form such aggressive biofilms. Deciphering the strategies of bacterial pathogens is crucial for the development of new approaches to fight them."
Reference material: What Is: A Biofilm
Additional information: The study is part of the National Centre of Competence in Research (NCCR) "AntiResist" and was conducted in collaboration with the École Polytechnique Fédérale de Lausanne. The aim of this research network is the discovery of new antibiotics and the development of novel strategies to combat antibiotic-resistant pathogens.
Published in journal: Cell
Title: Biofilm formation on human immune cells is a multicellular predation strategy of Vibrio cholerae
Authors: Lucia Vidakovic, Sofya Mikhaleva, Hannah Jeckel, Valerya Nisnevich, Kerstin Strenger, Konstantin Neuhaus, Keerthana Raveendran, Noa Bossel Ben-Moshe, Marina Aznaourova, Kazuki Nosho, Antje Drescher, Bernd Schmeck, Leon N. Schulte, Alexandre Persat, Roi Avraham, and Knut Drescher
Source/Credit: University of Basel | Katrin Bühler, Heike Sacher
Reference Number: mcb061223_01
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