Bacterial decoys and COVID defensosomes
If you look up the word ‘decoy’ in the Encyclopedia Britannica, you’ll find the following explanation:
decoy, deceptive device used to draw an enemy away from a more important target. Active decoys are the principal method of self-defense for military aircraft and intercontinental ballistic missiles (ICBMs). Passive decoys, or dummies, are used to deceive visual intelligence such as photo reconnaissance.
Next comes a brief example of an active decoy, and specifically how decoys can protect against antiaircraft missiles:
The main threats to modern military aircraft are antiaircraft missiles, which travel faster and maneuver better than the best jet fighters. Heat-seeking missiles are designed to follow heat sources such as the jet exhaust of a modern aircraft. To elude these missiles, a jet may release active decoys called flares, which are tubes containing magnesium that burn with an intense white heat. Because flares initially burn hotter than jet exhaust, they may confuse the missile by offering it several hot targets, giving the aircraft a chance to escape.
But it turns out, we humans were not the first to come up with the idea of an active decoy.
Our immune systems got there first.
Today on Microbial Mondays, I want to share with you a story from a recent paper published in the scientific journal Nature, which describes how active decoys released by our cells can protect us against potentially deadly toxins released by bacteria in much the same way that flares might protect against antiaircraft missiles. But what do these cellular “flares” look like?
I’ve written before about extracellular vesicles on Microbial Mondays, and how they can likely be used as a sort of mailing system amongst cells. This Nature paper by Keller and colleagues now suggests that exosomes, one particular sub-type of extracellular vesicles, have a whole other functionality beyond being mere letters from cell to cell. Their data shows that exosomes, which are made up of a fatty membrane with proteins embedded in that membrane, can also act as active decoys that trap bacterial toxins to prevent cells from being injured. Accordingly, the authors give a catchy new name to these active decoy exosomes: ´Defensosomes’.
In my head, I hear ‘DEFENSOSOMES’ in a deep, echoey, super-hero-style voice. I hope you did too.
In particular, the authors of this paper show that defensosomes can protect against so-called ‘pore-forming’ toxins that some bacteria, such as Staphylococcus aureus, produce. These toxins act by poking holes in cell membranes – ‘forming pores’ in scientific parley – which as you might imagine can kill those target cells. The battle between our cells and pore forming toxins is kind of like a microscopic knife fight – the toxins are stabby, and our cells try to avoid them.
What I found especially exciting, is that Keller and colleagues found that upon sensing the presence of dangerous bacteria, for instance by sensing the presence of bacterial DNA, cells can boost the amount of defensosomes that they spit out, in an effort to basically mop up bacterial toxins floating about in your body. More defensosomes in your body means more active decoys to grab the attention of the toxins, before those toxins ever hit any of your cells. Their findings are especially convincing because they not only show that defensosomes are produced by both cell lines and by real live mice, but they also dig into the mechanism behind how cells build their defensosomes. I won’t get into the nitty gritty mechanism here, but I was pretty excited to see that autophagy (my favourite cellular pathway) has a role to play in it.
Anyways, at the end of the paper, the authors comment that, “Given that the origin and regulation of extracellular vesicles remain poorly defined, a detailed understanding of the cellular response triggering the production of defensosomes during infection may reveal opportunities to leverage their unique properties to combat bacteria and other pathogens.”
And indeed, it looks like defensosomes - as Keller et al. seem to have guessed as per their inclusion of the phrase 'other pathogens' - might be involved in defense against viruses as well as bacteria.
Remember how I mentioned earlier that exosomes are made up of fatty membranes with some proteins stuck into that fat? Well, interestingly, one of the surface proteins on defensosomes produced in response to bacterial DNA is 'ADAM10', the very protein to which pore-forming toxins like the 'α-toxin' produced by methicillin-resistant Staphylococcus aureus (MRSA) bind.
And according to a recent pre-print manuscript, defensosomes specifically displaying ACE2, the ‘doorbell’ that SARS-CoV-2 must ring to enter our cells, are released as active decoys during COVID-19 infections. Do keep in mind, though, that this is a pre-print manuscript that the authors have uploaded to biorxiv - it has yet to be peer reviewed. In any case, though, it is a very interesting development in the field of extracellular vesicles, and perhaps we will be hearing more about defensosomes (and maybe even making synthetic defensosomes as a treatment option?!) in the future!
Until next time,