A new way out!

April 01, 2019

Protein secretion is used by all cells to deliver proteins to different cellular compartments. In bacteria, proteins secreted to the extracellular milieu play key roles in a multitude of important processes including virulence, biofilm formation, adhesion, interactions between bacteria in microbiomes, host-microbe interactions, adaptation and motility. In a recent publication in Nature Communications, scientists from The Max Planck Institute for Terrestrial Microbiology together with scientists from the University of Montpellier describe a novel system for protein secretion by bacteria. 

A new way out: Novel system for protein secretion by bacteria.

Protein secretion represents a formidable challenge to cells because proteins have to cross a membrane. In Gram-negative bacteria, protein secretion to the extracellular milieu represents an even bigger challenge because proteins have to cross two membranes. As it turns out, this challenge is overcome in two ways, i.e. either a protein is secreted in a one-step mechanism directly from the cytoplasm or in a two-step mechanism in which the protein is first translocated across the inner membrane to the periplasm and then across the outer membrane. 

The research group of Lotte Søgaard-Andersen at the Max Planck Institute in Marburg aims to understand how bacteria deal with changes in the environment. To this end, they study how myxobacterial cells respond to starvation with the formation of spore-filled fruiting bodies. The Søgaard-Andersen research group previously identified the secreted protease PopC as essential for fruiting body formation. However, it was not clear how the protein gets out of the cells.

Dr. Nuria Gómez-Santos in the Søgaard-Andersen lab addressed precisely this question in her research. “When we started we thought that one of the known one-step secretion systems would be involved in secretion of PopC; however, we quickly realized that this was not the case and that PopC is secreted in a two-step process” explains Dr. Gómez-Santos. The scientists also found that none of the known systems for secreting protein across the outer membrane was involved in PopC secretion. Dr. Gómez-Santos explains “Almost like detectives we then had to zero in on candidates for the novel secretion system”. This search culminated in the finding that a TonB-dependent transporter named Oar is essential for secretion of the PopC protease from the periplasm across the outer membrane to the extracellular milieu. TonB-dependent transporters are ubiquitous outer membrane proteins in Gram-negative bacteria. Some of these transporters are directly involved in the import of micronutrients such as iron, nickel and B12 compounds, macronutrients such as carbohydrates, and large bacteriocin toxins. These import processes are energized by the proton motive forceacross the inner membrane via the so-called Ton system in the inner membrane. Based on their work, the scientists have proposed that Oar in the outer membrane together with the Ton system in the inner membrane may directly secrete PopC across the outer membrane. 

TonB-dependent transporters are among the most widespread outer membrane proteins in Gram-negative bacteria, with some species containing more than 100 paralogs of this protein family. However, the function of most of these transporters is not known. Based on their recent findings, the scientists speculate that some of these proteins may not only be involved in import but additionally, or exclusively, in protein secretion across the outer membrane.

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