This post is written by Dr Faraz Alam, formerly a London-based member of the Bioluminescent Superbugs Lab and describes one of the figures in a PLOS One paper from his PhD studies.
There are moments in science that you can never really prepare for. There are times when you go into an experiment with expectations that get upended completely. This is the story of one of those moments.
I was studying a bacterium named Streptococcus pyogenes, a very versatile pathogen that can cause sore throats and skin diseases, and can infect wounds. S. pyogenes is also the only bacterium that has been documented to spread through farting (1,2)! But you may recognise it by its most extreme manifestation – necrotizing fasciitis, the flesh-eating disease. The aim of my PhD was to make glowing S. pyogenes so we could track it during an infection.
The experiment I was setting out to do on this particular day was to directly compare the amount of light produced during a nasal infection with the numbers of bacteria present. That way, I could build a curve that I could use to estimate the numbers of bacteria within the nose based on the light they produce. At least, that was the point of the experiment, but as is often the case in science, things don’t always go according to plan. It was a Monday morning, and I’d been working through the weekend to get this experiment finished, when something weird happened. Something that I hadn’t expected, and could barely explain. The nose of the mouse was glowing, as I had expected because that was where the bacteria were supposed to be causing an infection. But another signal was detected in the mouse’s ….*ahem*
The photo pretty much tells the whole story. The mouse did most of the work, I merely took the pictures. The following exchange occurred after I e-mailed this image to Siouxsie.
Regrettably the “self-stimulating” mouse hypothesis had a very short shelf life. If that was the only thing that was going on, then wouldn’t all of the mice have glowing vagina’s? I should point out that mice naturally groom themselves, and eat their own faeces, which means that all of the mice should have been able to transfer the bacteria in their nose to their genitals. But some mice were more susceptible than others, and my current hypothesis is that it is to do with the specific stage of their menstrual cycle that actually makes it a very hospitable place for bacteria.
The mouse vaginal tract is believed to actually use bacteria as the first line of defense, primarily a bacterium named Lactobacillus. At certain points of the menstrual cycle, it is believed that the oestrogen causes the vagina to produce sugars which the Lactobacillus can feed on. This is meant to boost its population, and help it defend against infections from nastier bacteria. However, other bacteria can take advantage of this system if given the opportunity. In this case, I suspect that the bioluminescent S. pyogenes has snuck in and begun to colonise this area.
The reason why it happens so rarely is because of something called the Lee-Boot effect. Mice tend to use pheromones to determine whether to start their menstrual cycle. The most well documented example of this is the Whitten effect, where mice can synchronise their cycles when they have regular exposure to the scent of male mice. There was a failed attempt to extrapolate this behaviour into humans known as the McClintock effect that has actually been disproven because humans don’t produce pheromones, nor has it been proven that humans have a functioning pheromone sensing organ (called a vomeronasal organ) to detect them.
Mice on the other hand have a number of different responses to pheromones. When female mice are housed together with no males present, they can produce pheromones that suppress the menstrual cycle. This kind of suppression is known as the Lee-Boot effect. Considering that the mice in these experiments were all female, it is likely that they all are exposed to the Lee-Boot effect. This is my best guess as to why only a relatively few mice in each cage had glowing genitalia during the course of an experiment.
You won’t see this speculation in an actual paper, because as nice an idea as it is, I didn’t have comprehensive evidence to back it up. I did a few follow up experiments messing with mouse pheromones and hormones, but I could never reliably predict when this kind of colonisation could occur, nor could I reliably trigger it. I was fully prepared for it to live out the rest of its days in the junk drawer. Everything changed when my paper went to be reviewed. I had submitted a paper to PLOS One showing off how these bugs can be used to show whether a vaccine is working or not (3). The reviewer wanted us to show exactly why bioluminescence was such a big deal. Suddenly, the true value of this data revealed itself.
That glowing vagina was a demonstration of how versatile Streptococcus pyogenes is as a pathogen. It showed how bacteria can travel between different organs of the body, and turn up in the least likely places (3). Even if I couldn’t comprehensively explain how these genitals came to glow, the fact that they were glowing was important enough in its own right. You may laugh at the glowing vagina, but it is powerful demonstration of how diseases can take unexpected turns, and glowing bacteria can show us what happens when they do.
1. Schaffner W, Lefkowitz LB Jr, Goodman JS, & Koenig MG (1969). Hospital outbreak of infections with group a streptococci traced to an asymptomatic anal carrier. The New England journal of medicine, 280 (22), 1224-5 PMID: 4889553
2. McKee WM, Di Caprio JM, Roberts CE Jr, & Sherris JC (1966). Anal carriage as the probable source of a streptococcal epidemic. Lancet, 2 (7471), 1007-9 PMID: 4162660
3. Alam FM, Bateman C, Turner CE, Wiles S, Sriskandan S (2013) Non-Invasive Monitoring of Streptococcus pyogenes Vaccine Efficacy Using Biophotonic Imaging. PLoS ONE 8(11): e82123. doi:10.1371/journal.pone.0082123