The common parasite you’ve probably never heard of
After viruses, it’s the second biggest cause of sexually transmitted disease in the world - but though you may have heard of gonorrhoea, syphilis and chlamydia, trichomonas is a pathogen that seems to sneak under the radar.
After viruses, it’s the second biggest cause of sexually transmitted disease in the world - but though you may have heard of gonorrhoea, syphilis and chlamydia, trichomonas is a pathogen that seems to sneak under the radar. This weird protist threatens not just our sexual health but the lives of many animals, from cows to songbirds. Here’s how Earlham Institute scientists have been getting to grips with it.
This article forms part of our Marrying Microbes: in sickness and in health series exploring the topic of health research.
“Even for a protist, trichomonas is weird,” says Dr Ross Low, a postdoctoral scientist working in the microbial genomics group at the Earlham Institute. Low studies Trichomonas gallinae, a protist parasite that severely threatens birds such as greenfinches.
Protists - a group containing millions of mostly single-celled organisms that are barely related to one another and come in all shapes and sizes - are weird enough already. So why is trichomonas particularly strange?
“They don't have mitochondria,” Low explains. “They are odd things. They only exist in places where there is little or no oxygen - in the mucosal membranes of cattle or birds, for example.”
Most protists, much like you and me, have mitochondria. In these tiny cell factories, oxygen from the air we breathe is used to unlock energy from sugar molecules, allowing us to do things like moving, digesting food, and mating.
Trichomonas, however, has hydrogenosomes - an alternative cell factory that uses hydrogen, rather than oxygen, as a final electron acceptor. That allows trichomonas to inhabit places where oxygen is absent.
Another mucosal membrane lacking oxygen lines the urogenital tract, which provides a home for a rich variety of microorganisms - the aptly named Trichomonas vaginalis among them.
“Trichomonas vaginalis is the most common non-viral, sexually-transmitted infection worldwide,” says Dr Sally Warring, who works alongside Low. Warring has recently published a paper on the work she did on this prevalent pathogen with Professor Jane Carlton at New York University.
Found in both men and women, the World Health Organization estimates there are around 156,000,000 cases of Trichomonas vaginalis worldwide at any one time. Many of the carriers feel completely healthy but around 30% of people show symptoms, which can be particularly dangerous for women.
“Trichomonas, like many other organisms, needs to eat to survive,” explains Warring. “That tends to be bacteria cells, or cells of the urogenital tract, which can lead to some bad outcomes - especially during pregnancy.”
Trichomons vaginalis, the single-celled protist that causes Trichomoniasis
Pregnant women suffering from trichomoniasis - the disease caused by Trichomonas vaginalis - can give birth prematurely, and babies born to mothers with trichomoniasis can have low birth weights. Despite this, trichomoniasis is a disease that largely goes under the radar.
“It’s extremely common and yet we know very little about it,” reflects Warring, who adds that trichomonas goes undetected partly due to the complexities of identifying it. “You take cells from the cervix or from the male urogenital tract, put these on a microscope slide, and the clinician has to actually spot live trichomonas cells. It requires a high level of skill.”
That’s one area where genomics can come in very handy.
“When we have the genome of an organism like Trichomonas vaginalis, which we've had since 2007, we can develop tools to use genetic tests to identify who has trichomonas and who doesn't,” says Warring. “A number of those tests are in development.”
Cracking the trichomonas code
Once it has finally been diagnosed, trichomoniasis is treatable with antimicrobial drugs such as metronidazole. Unfortunately, however, this also kills the healthy bacteria lining the urogenital tract - and trichomonas itself is increasingly showing signs of resistance to the drug.
That’s why it’s important to study the parasite - to find new ways of treating it in a more targeted way. In her work with Professor Jane Carlton at NYU, Warring looked at the genome of Trichomonas vaginalis and how it functions - revealing yet more oddities about this particular parasite.
One of the things that's unusual about trichomonas is that a lot of its genome is made up of these things called transposable elements, which is a type of selfish genetic element
“One of the things that's unusual about trichomonas is that a lot of its genome is made up of these things called transposable elements, which is a type of selfish genetic element,” Warring explains.
Transposable elements - also called transposons - are small, self-replicating bits of DNA that invade a genome and contain genes that are required for their own replication and survival. Many of them are related to viruses. They make up about 45% of the human genome, but seem out of place in that of a protist.
“It’s unusual for organisms like this to have lots of transposable elements,” Warring continues. “Often, parasites are under evolutionary pressure to have quite a streamlined genome. Parasites get a lot of the things they need to live from feeding off their host organisms, so they can also cut down on genomic resources by just getting products from the host.
“An ongoing question in the trichomonas community is why these things are there, why they have proliferated in this one particular lineage, and whether they play a functional role in the parasite or not, because it's so unusual for a parasitic protist to have these things. Others have a few, but plasmodium, the malaria parasite, has none whatsoever!”
With Carlton, Warring managed to make some inroads into these questions by looking at small RNAs, which are usually present in genomes to regulate other things, such as genes. Warring wondered whether these might help Trichomonas vaginalis control the transposable elements.
“We found a group of small RNAs that are expressed in Trichomonas vaginalis,” reveals Warring. "We found that these small RNAs tend to map to the transposable elements. We think that somehow they function to reduce the expression or the functioning of these transposable elements.”
The World Health Organisation (WHO) estimate that there are 376 million new STI infections every year, with 156 million of those diagnosed with trichomoniasis.
The evolution of a killer
While Warring has been tackling the weird side of trichomonas, Dr Ross Low has been hard at work with Dr Kevin Tyler at the University of East Anglia applying comparative genomics to understand the evolution of this strange parasite - particularly in light of its devastating effect on British greenfinches.
In the last ten years, greenfinch numbers in the UK have plummeted by almost 60%. “They're in danger of being moved straight to the UK Red List of endangered species,” Low laments.
“Trichomonas could very well cause the extinction of UK greenfinches. And once the UK greenfinch population gets too low, there's no reason that the disease wouldn't spread to other species that are more abundant.”
Trichomonas gallinae has long caused disease in birds. It’s known as frounce in pigeons and canker in greenfinches. It’s likely to have caused disease even in the long-dead ancestors of our modern day birds - the dinosaurs - millions of years ago. A new variant affecting British greenfinches, however, is particularly devastating.
“Historically, it was probably something that birds picked up periodically, or seasonally - a bit like a cold,” says Low. “This new variant has suddenly caused a dramatic drop in the numbers of greenfinches because it gets so bad that their throats swell up and eating or drinking becomes impossible.”
Greenfinches are particularly susceptible to the parasite Trichomonas gallinae which causes their throat to swell up so they can’t eat or drink
Trichomonas could very well cause the extinction of UK greenfinches. And once the UK greenfinch population gets too low, there's no reason that the disease wouldn't spread to other species that are more abundant.
Low is studying the differences between this variant and other forms of Trichomonas gallinae to try to understand what has made it so lethal. Although it’s too early to say, it might even be that this is an entirely new species.
“One of the striking differences is that it really is very, very different from the normal Trichomonas gallinae that we would expect to find. We're not entirely sure at this stage if that's normal for these organisms, whether they all look very different from each other, or whether this is a particular case where it just looks very different and strange.”
Low likens his research to the current COVID pandemic, whereby scientists are aiming to keep tabs on mutations and the spread of new variants through the population.
“There's been a lot of talk about this in the news recently because of COVID-19. Generally speaking, the more transmissible an infection is, the less deadly it is. But we know that Trichomonas gallinae is transmitted through bird baths.
“If it can get into a bird bath, it infects a new bird. There's no reason not to kill that host, because it will always have the ability to be transmitted through the birdbath.”
This insight, plus the fact that it can take up to two years for birds to finally succumb to Trichomonas gallinae, means that many birds are at risk - all the way along the food chain.
“There's always the risk that other bird populations could be affected,” says Low. “It can also affect birds of prey. They won't get it from bird baths, they'll get it from eating finches.”
Finding a cure
Trichomonas vaginalis and Trichomonas gallinae are just two among a number of devastating pathogens that affect humans and other animals alike. Low, along with other scientists in the group, work on other common pathogens such as trypanosomes, which cause deadly diseases including African sleeping sickness and Chagas disease.
What we learn from any of these protists - and the oddities of their genomes - can help us to find better ways of learning about and fighting back against them.
“The more you understand about a parasite and how it functions, the more hopefully the more opportunities you have to develop tools that can interfere with it,” says Warring. “Protist parasites are eukaryotic, like humans, so you have to be really careful that the things you're using to treat the parasite don't have off-target effects in the host.
“The more things we can find that might be specific to the parasite, the greater the chance we’ll figure out a way to use that to our advantage to control the parasite.”
For both Warring and Low, the power of genomics - the study of DNA and the development of novel protocols and discoveries - is a powerful tool to tackle not only parasites such as trichomonas but to help the advancement of science.
“I get asked all the time: ‘why do you bother doing what you do?’,” says Warring. “‘What's the point of another genome?’
“When I started working on trichomonas, one of the reasons I could do the work I did was because my supervisor, Professor Jane Carlton, had already sequenced the genome, so that genome sequence was available to us.
“I think that's the whole point of producing genomes and genomic data - they’re not just for my own use. I might use them, but I'm producing them for the community to use. They're tools for the community that can solve problems now and in the future.”