14 DAY TRIAL // Cryptococcal meningitis, a severe infection of the tissue covering the brain, i.e. the meninges, is estimated to kill around 600,000 people annually. The infection is caused by one of two species of fungus, Cryptococcus neoformans or Cryptococcus gattii.
Usually, people inhale these microorganisms. In the case of healthy individuals, the fungi do not spread beyond the lungs. In the case of people with a compromised immune system, however, they can move into the blood stream and then push through the blood-brain barrier.
To treat this fungal disease, medical experts must first know exactly what it is that they are dealing with. Hoping to gain a better understanding of how the infection debuts and then progresses, researchers at Duke Medicine carried out a series of experiments on baby fish.
They infected them and then watched them die
The Duke Medicine researcher team performed their experiments on zebrafish larvae, which they chose because they have a transparent body and so they could watch what was happening inside them.
The scientists first infected the larvae with Cryptococcus fungi and then observed in real time as the microorganisms took over their brain. They even made a video, which you can find below.
Made red by a transparent tracer, the fungi are seen moving through tissue, blood vessels and then all the way deep into the brain. In this video, immune cells dubbed macrophages, which are designed to engulf and destroy cellular debris or invaders, are shown in blue. Blood vessels appear in green.
“What's impressive is that, unlike in a mouse or rabbit, you can actually see the organism producing disease in the live animal. Day-by-day, it's growing and moving throughout the body. You can't see this anywhere else,” said Duke University School of Medicine specialist John R. Perfect.
So, what's the point of such experiments?
In a report in mBio, a journal of the American Society of Microbiology, the Duke Medicine scientists behind this investigation explain that, apart from having clear bodies, zebrafish larvae are also permeable; in other words, they can absorb drug compounds through their skin.
What this means is they can be used to test the effectiveness of various chemical concoctions designed to treat Cryptococcal meningitis. Basically, zebrafish larvae are the perfect test subjects to watch drugs developed to address this fungal disease at work.
“It will allow us to screen libraries of drug compounds relatively quickly. We can also develop and test mutant strains of Cryptococcus in these larvae. This can teach us which factors play a role in infection and those could be therapeutic targets in the future,” said researcher David Tobin.
Interestingly, the scientists propose that zebrafish could also be used to gain a better understanding of other infectious diseases. All specialists would have to do would be to adapt the zebrafish model to keep tabs on whatever invading microorganisms they want to study.
