Biologists from ETH Zurich have discovered speargun-like molecular injection systems in two kinds of bacteria and have described their structure for the first time. Microbes are used by the nanomachines for the interaction between cells and might one day be useful as therapeutic tools.
Many bacteria use advanced molecular injection tools to accomplish various tasks. For example, a bacterium inoculates certain molecules into a worm larva through a nanomachine composed of proteins, which initiates the transformation of the larva into an adult worm. Other bacteria also use such molecular weapons to kill other strains of bacteria or insect larvae, or they defend themselves against scavenger cells.
In the journal Nature Microbiology, scientists from the group of Martin Pilhofer, a professor of Molecular Biology and Biophysics at Zurich, who specializes in molecular injection techniques, have just described two new systems: one one one from cyanobacteria, also known as blue-green algae, and the other from the marine bacterium Algoriphagus machipongonensis.
The so-called contractile injection systems (CISs) have evolved dramatically and are now available for purchase. This information provides you with information about the evolution differences between different injection system methods.
These CISs function like molecular syringes. When the outer sheath module of the nanomachine contracts, an internal, hidden tube filled with proteins is shot out. These proteins are either injected into the environment or directly into a target cell.
A surprising anchoring in the cell
A novel CIS, discovered in cyanobacteria, was not anchored in the cell membrane or loosely floating inside the cell as planned, but was attached to the so-called thylakoid membrane, where photosynthesis occurs.
"That was the greatest surprise for us," says Gregor Weiss, the lead author of a research on the cyanobacterial injection system. Despite this unusual localization, the CIS anchored in the thylakoid membrane referred to as tCIS fulfill their purpose. If cyanobacteria are stressed, such as excessive salt concentrations in the water or ultraviolet light, the outer cell layers detach. This exposes the outside-facing tCIS, who are eager to fire
Several molecular spear guns are unexpectedly common, which according to Weiss suggests an important role in the life cycle of cyanobacteria. He suspects that the tCIS might play a role in the programmed cell death of individual individuals in these multicellular cyanobacteria.
Extracellular injection system
Jingwei Xu and Charles Ericson, both members of Pilhofer''s organization, discovered and describe a CIS produced by the marine bacterium Algoriphagus machipongonensis, which is not intended for the cell at all, but rather was later released into the environment to act on target cells in the area.
In high resolution, researchers used cryo-electron microscopy to determine the structure of this specific subtype of ejected CIS (eCIS), which no other research group had previously been able to do. "The newly discovered nano machines give us clues that contractile injection systems are more common than previously thought," says Ericson.
From molecules to whole bacteria
These tests are remarkable because of their interdisciplinary, diverse approach: from bacteria collected in natural ecosystems to atomic-level models of their respective CIS. "This work very nicely shows how different techniques can be utilized to get an idea of these systems and structures," says Weiss. In addition, the study highlights that there is a need to shift from laboratory strains to environmental samples in order to understand the role of injection systems in the life cycle.
Future use in biomedicine
These two studies help researchers understand how CIS-producing organisms affect their environment. In addition, different sites in these systems demonstrate how each CIS is organized for a specific purpose: specialized hair-like receptors allow targeted binding of target cells, variable loading of these molecular sparguns causes different cellular effects, and distinct anchoring mechanisms allow the CISs to very different modes of action.
Future researchers may modify biomedicine''s modular structure so that a molecular speargun may target specific cell types and fire medications or antimicrobials, according to this principle.
References:Weiss GL, Eisenstein F, and Kieninger AK et al. Structure of a thylakoid-anchored contractile injection system in multicellular cyanobacteria. Nat Microbiol. 2022;7(3):386-396. doi:10.1038/s41564-021-01055-y
Xu J, Ericson CF, Lien YW, and others. Algoriphagus machipongonensis: an extracellular contractile injection system. Am J Microbiol. 2022;7(3):397-410. doi:10.1038/s41564-022-01059-2