Previously, it was assumed that bacteria form biofilms to defend and protect themselves. Now, a new study by researchers at the University of Basel, Switzerland, has 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. Their study provides new insights into the infection strategies of pathogens.

The findings are published in Cell in an article titled, “Biofilm formation on human immune cells is a multicellular predation strategy of Vibrio cholerae.”

“Biofilm formation is generally recognized as a bacterial defense mechanism against environmental threats, including antibiotics, bacteriophages, and leukocytes of the human immune system,” wrote the researchers. “Here, we show that for the human pathogen Vibrio cholerae, biofilm formation is not only a protective trait but also an aggressive trait to collectively predate different immune cells. We find that V. cholerae forms biofilms on the eukaryotic cell surface using an extracellular matrix comprising primarily mannose-sensitive hemagglutinin pili, toxin-coregulated pili, and the secreted colonization factor TcpF, which differs from the matrix composition of biofilms on other surfaces. These biofilms encase immune cells and establish a high local concentration of a secreted hemolysin to kill the immune cells before the biofilms disperse in a c-di-GMP-dependent manner.”

To better understand biofilm formation on immune cells, the researchers focused on macrophages. “Bacteria that accidentally encounter a macrophage attach to the cell’s surface using a kind of a ‘feeler’,” explained first author Lucia Vidakovic, PhD, a postdoctoral scientist at the University of Basel. “Subsequently, the bacteria start to divide and intertwine their feeler-like appendages.”

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,” said 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.

The researchers established a human intestinal organoid model to demonstrate that V. 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,” added Knut Drescher, PhD, associate professor, University of Basel. “In a 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.”

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