Bacterial “bubbles” hitchhike on cellular protrusions to reach the cell surface

“This is a mechanism that increases the understanding of how bacteria and cells interact and, by extension, how we understand and fight infections,” says Anna Arnqvist, professor at the Department of Medicinal Chemistry and Biophysics at Umeå University, who led the study.

Drones with delivery

All living cells can release nano-sized fluid-filled structures that resemble “bubbles”, so-called vesicles. Bacteria also release such vesicles, and despite their small size, they can carry everything from toxins to proteins and DNA that affects how the receiving host cell reacts.

“The vesicles act as messengers between each other and to cells, much like tiny drones that deliver their content,” explains Zia Ur Rehman, first author. He was postdoctoral fellow at the Department of Medicinal Chemistry and Biophysics at Umeå University when the study was carried out.

While previous research has focused on a better understanding of how cells take up vesicles and what effects they cause, the question of how the vesicles reach the surface of the cell body where the uptake occurs has remained unanswered.

Not moving randomly

The new study shows that vesicles near host cells do not just drift around randomly. Instead, they hitchhike on thin, hair-like protrusions on the cell surface, called filopodia. Filopodia are rich in actin proteins and play important roles in cell movement, contraction and sensing of the environment. Anna Arnqvist and her colleagues discovered that vesicles utilize filopodia either by "surfing" along them, much like sliding down a railing, or by being actively pulled inward when the filopodia contract.

This mode of transport efficiently captures vesicles from the surrounding environment and moves them from the outer edge of the cell to the cell body, where they can internalize and thereby deliver their contents to the host cell.

Using advanced high-resolution microscopy techniques, the team was able to observe vesicles interacting with filopodia in real time and even measure their speed as they surfed forward or were pulled inward.

“The speed when they surfed forward was an average of 1 nanometer per second. When they were pulled inward, it was faster, an average of 30 nanometers per second, which means it moved about its own length in one to two seconds,” says Zia Ur Rehman.

Universal strategy in bacteria

“Importantly, we saw that the vesicles use the same transport mechanism regardless of which bacterium the vesicles came from, or which tissue the recipient cells belonged to. This suggests that this is a universal strategy that bacteria use,” says Anna Arnqvist.

Because vesicles mimic the surface of their parent bacteria and carry a wide range of molecules, they can affect host cells in many ways. In addition to delivering harmful substances, the vesicles can act as "decoys" to protect bacteria from attack by the immune system.

Preventing and treating infections

Since bacterial vesicles already play a key role in infection biology medicine, for example as delivery systems for drugs or vaccines, this study provides important new knowledge about the very first contact with the host cell.

“Our long-term goal with the research is to understand how bacterial vesicles hijack host cells and translate this knowledge into new methods that can prevent or treat infections,” says Anna Arnqvist.

The study has been published in the Journal of Extracellular Vesicles. It has been funded by the Swedish Cancer Society. The analyses were carried out at the Biochemical Imaging Centre Umeå (BICU) and Umeå Centre for Electron Microcopy (UCEM) at Umeå University.

About the scientific article:

Ur Rehman et al: Bacterial extracellular vesicles exploit filopodial surfing and retraction mechanisms to reach the host cell body in an actin-dependent manner. 2025. J Extracellular Vesicles 14:e70107

https://doi.org/10.1002/jev2.70107

For more information, please contact:

Anna Arnqvist, Department of Medical Biochemistry and Biophysics, Umeå University                                      https://www.umu.se/en/research/groups/anna-arnqvist/

Zia Ur Rehman, Department of Biotechnology and Genetic Engineering, University of Science and Technology, KUST, Kohat, Pakistanhttps://www.kust.edu.pk/kust/pages/administration/index.php?depCode=BTGE-KUST&type=1