Journalist: Yumnah Jafri
Yumnah Jafri: Welcome to SciSection. My name is Yumnah Jafri and I am the journalist for the SciSection radio show broadcasted on CFMU 93.3 FM radio station. We are here today with Dr. Xu from the Department of Biology here at McMaster. Thank you so much for taking the time to meet with me today, Dr. Xu.
Dr. Jianping Xu: Thank you for your interest. I'm happy to be here.
Yumnah Jafri: We'll give you some time right now to introduce yourself to our listeners, who may not know who you are or the amazing research you're doing.
Dr. Xu: Sure. My name is Jianping Xu, but people here typically call me JP. I joined the McMaster faculty in 2000, starting as an assistant professor and then transitioning to the associate professor and the full professor in 2012. My research is on fungal biology, and we have been looking at the fungi from different perspectives, from ecological, environmental, evolutionary, and genetic perspectives.
Our goal is to understand how fungi evolve and how various ecological and environmental factors impact the evolution.
Those kinds of evolutionary processes that they are undergoing will also have an impact on human health and human welfare. So, we’ve been looking at fungi that are consumed by people as delicious food and fungi that cause se severe diseases in crops that we grow, and we consume. To animals that are keystone species in our environment, and then of course to humans ourselves. We look at multiple species and how their genetic distribution spatially and the temporally impact human populations and wildlife as well as crop populations.
And my background, I grew up in China. As you can see that the last name Xu is quite often difficult for people to pronounce. It's pronounced Xu. I did my undergraduate over there and also masters over there. Then, I came to Canada in 2000 in 1991, first as a masters student at the University of Toronto, and then switched to a Ph.D. I graduated in 1996 and from ‘97 to 2000 I was a postdoc at the Duke University Medical Center in Durham, North Carolina, in the US, and then moved over here in 2000 at McMaster.
Yumnah Jafri: Thank you so much for that overview. You did mention that you do a lot of research on human fungal pathogens, but what piqued your interest in the first place in this specific area in research?
Dr. Xu: Human fungal pathogens are a group of unique species that are phylogenetically and evolutionary not clustered.
They are distributed among different fungi, so that suggests that fungal pathogenicity to humans have originated multiple times.
Some of those have relatives that are non-pathogenic and some of them have relatives that are living with the rocks. In environments that typically we would not consider having any in human presence or even mammalian presence.
But what has happened is that the human populations have been changing. Partly due to medical advances we are living longer, and the underlying conditions are becoming more and more prevalent. Including cancer treatment and cancer patients, and organ transplant on patients and AIDS patients, elderly people...
So, we have an increasing population of humans that become more and more susceptible to a variety of infections. Not only fungi, but bacteria as well. But different from bacterial and viral pathogen to humans, many of the fungal pathogens are opportunistic in that, they don't typically cause diseases in us. Almost all the fungal pathogens can be found in the environment, and most of us are exposed to those fungal pathogens regularly. Like for some of them, exposed to them daily, in often high dosages. So, for most of us who are not immunocompromised, immunocompetent people, healthy people, we can easily defend ourselves against exposure.
But for immunocompromised people, including cancer patients, transplants, elderly, etc. the immune system might not be able to defend it. One of the understated reasons for their persistence, is that they can survive within a diversity of environments. They can produce stress resistant particles that can live in the environment for a long, long time without ever being killed, for example.
Including resistance to UV, resistance to high temperature, and they can become airborne producing billions of spores on one petri plate alone. Another factor that is often not appreciated, is that evolutionary fungi including human fungal pathogens are evolutionary very closely related to animals. Therefore, their cell structure, the membrane, their genes that control most of the essential functions are very similar between animals and the fungi.
Therefore, it's very difficult to find appropriate drugs that will only kill the fungi but have little side effect to humans. So together, those kinds of ability present a very important and probably persistent dilemma for us, how to deal with these human fungal pathogens. Together those reasons, I think because of the increasing importance, which I can get into if you want me to say some statistics. They're going to be increasingly important in our daily lives and in a society as an important public health issue in the future.
Yumnah Jafri: I didn’t know much about the cell structure of fungal pathogens and how they're so similar to the animal structure. I can imagine, as you mentioned, it's very hard to find medication that specifically targets these pathogens, so it's really important to research more on these pathogens then.
Dr. Xu: One of the model fungal species is called Saccharomyces cerevisiae, which is yeast unicellular fungus. It's a brew yeast and it’s also called the baker's yeast. It's commonly used in bread making, wine, making, beer making, etc. That unicellular yeast, that's 40% of the genes have homologs in humans. Very, very genetically highly similar in many, many features.
Yumnah Jafri: That's crazy. I personally use yeast to make bread and I don't think too much about it, but that's incredible. Is there a specific reason why you wanted to research Cryptococcus neoformans, which is another fungal pathogen, and Aspergillus fumigatus. Was there a specific reason why you specifically focused your attention on these pathogens?
Dr. Xu: There are few reasons for Cryptococcus. When I started my postdoc, the lab that I worked with and the group at Duke, was very well known for Cryptococcus research. It's probably the center of research for Cryptococcus in the world. So, they collected a lot of strains from patients, and I contributed strains to their collection as well. We were looking at the global population structure and the evolution of this pathogen. Then use, because of the availability of strains in that center including genetically modified strains from molecular biology experiments, we were able to use those material for a variety of experiments to look at genetic mapping, which you learned in second year genetics, quantitative trait loci mapping, hybridization, and effects of hybrids in the environment. So, we were able to do a lot of research because of those close collaborations. And after I started my own lab here, I continued many of those areas of research including mitochondrial inheritance. I think I mentioned in 2C03 that in humans as well in most animals, mitochondria is uniparentally inherited. And all of us get our mitochondria from our mother. So, it's uniparental, but in this yeast, it is a fungus, a unicellular, there's no male-female morphological difference whatsoever…their mitochondria is also uniparentally inherited, just like humans. You can see there's a lot of similarity that pops up here and there.
That's allowed us to investigate the genetic basis for mitochondria inheritance in this species using this species, Cryptococcus neoformans as a model, and that allows us to actually identify the first genes in all eukaryotes that control mitochondria inheritance, which is a sex-determined gene.
So that was very, very cool. We have continued to use Cryptococcus neoformans as a model system to understand their evolution, their modes of reproduction in nature and in the lab, etc. So that's for Cryptococcus neoformans. Also, I should add. So that's one aspect in that we have all those materials due to collaboration; colleagues at Duke University and continued collaboration with colleagues over there. Another one, I was recently just about two weeks ago I was in Kampala, Uganda for the 11th International Conference on Cryptococcus and the Cryptococcosis. Especially the Cryptococcal meningitis, which is the infection of the brain by Cryptococcus fungus. It's responsible for about 20% of the mortality of AIDS patients. So, the huge burden of disease in sub-Sahara Africa, as well as in many other places where HIV is still an issue. It's a big public health issue. That's another reason is that it's very important medically.
So, that's Cryptococcus and I will get to Aspergillus fumigatus. Aspergillus fumigatus is among the most common modes in the environment, in our indoor environment, in our outdoor environment, and especially prevalent in places where organic debris are abundant, like in compost piles. Each year about 3-4 million people are infected, respiratory infection, and some of them get in blood. About 200,000-250,000 are killed by this fungal infection. So again, it's one of the major infections. And before I started to work on this fungus, I was interviewed by Canwest Media, Margaret Monroe for Canwest newspaper and the media group. So, at that time she was interested in whether there's anybody in Canada working on the drug resistance in this fungus or on this fungus. But purely just on this fungus. There was really nobody so. Her question was whether the application of agricultural fungicide in Canada pose a threat of driving the resistance to antifungal drugs in Canada, which potentially could impact human health and clinical treatment. At that time, there was no data in Canada. So, I said, ‘now we are going to look at this issue’ starting in Hamilton. I started hiring a few undergraduate thesis students…not hiring, actually few undergraduate thesis students joined my lab, and then we started isolating this fungus from soil samples from different parks in Canada, in North Hamilton, from trees and organic debris, etc. We didn't really find any evidence of triazole resistance, but we did find a very high prevalence of Amphotericin B tolerance and resistance. So, that was where we started. Then it expanded to a global collaboration with colleagues in many countries. Now we have the biggest research program supported by Faculty of Health Sciences and Institute of Infectious Diseases, to look at the global population structure of this fungus.
That's how we started looking at this.
These two fungi, Cryptococcus and Aspergillus fumigatus are two of the top four priority human fungal pathogen recently named by the World Health Organization and the other two fungi on the list.
There are four fungi on the top priority list. One is Candida auris, which we also work on in collaboration with international colleagues. Another one is Candida albicans, which I used to work on when I was doing my postdoc and then we just too busy with Cryptococcus. We dropped it. So, we have been working with all four-priority list fungal species over the last couple of decades.
Yumnah Jafri: Thank you so much for all that overview on what your lab is doing in relation to these fungal pathogens, specifically working on four of the most important ones, as you mentioned, said by WHO. I find it so interesting how, for Aspergillus, you mentioned that it has a very high mortality rate, but no one else had been working on researching this fungus before you, it seems like.
Dr. Xu: Very few people in Canada had looked at this fungus from a broad perspective, either genetically or epidemiologically.
Yumnah Jafri: It's really important research you're doing then. So, what would you say are the key takeaways from what you have learned at Xu Lab in relation to these pathogens you just mentioned, or what you've worked on in the past as well?
Dr. Xu: For both of those fungal pathogens, in fact, even for Candida auris or Candida albicans, they are genetically divergent lineages within each of those species. And those lineages differ in their virulence properties and in many ways also differ in their anti-fungal drug resistance properties. Therefore, identifying them, rebuilding those features are very important for the clinicians to determine what kind of drugs should be used and should not be used depending on the geographical location.
Another kind of broad take home message is that our humans, either through our activities or moving around ourselves, have been facilitating the dispersal of fungal pathogens, so that includes all four species.
For Candida Auris, we have identified Canada had at least three of the four lineages that are divergent from each other. But all of those are imported from somewhere else. For Cryptococcus, we have an outbreak that started about 20 years ago in Vancouver Island and that outbreak has now spread to Pacific Northwest and mainland B.C. That's cryptococcal outbreak. For aspergillus, it’s just practically everywhere. We found one strain from Northwest Territories close to Yellowknife that’s genetically and phenotypically almost identical to that from India that we analyzed 20 years ago. So, we believe those are the effects of anthropogenic activity-facilitated dispersal.
Yumnah Jafri: Do you mind going into a little bit more detail in what types of anthropogenic activity…
Dr. Xu: Certainly. Many of those fungi, because they're widespread in the environment,
those pathogens. When we go there, we're picking them up on our clothes, on our feet, in our hairs, potentially they are airborne. So, we pick them up and then when we go to a different place, we drop them. If the conditions are right, they will germinate and they will produce. And because of the frequent human travel, for example, when I mentioned in Northwest Territories, in the summer there's a huge demand to see Northern Lights. People will go there, and they attract international visitors. So, that could facilitate the dispersal events.
Yumnah Jafri: I see. For sure, that makes a lot of sense with the traveling.
Dr. Xu: And the trade. Food and other kinds of products. None of them are sterile.
All of them will carry, potentially, native microbes from where the products were made to the new place. So, it's just the fact of life. We just have the monitor how much that kind of human-assisted dispersal of fungal pathogens, how much effect that they would have on the local population and in the human population.
Yumnah Jafri: Very, very hard to kind of ban traveling, for example. But it's just something that I believe that we do have to monitor.
Dr. Xu: Even with strict protocols during COVID pandemic it’s still spreading.
Yumnah Jafri: Maybe taking a step back now into a more general category. What do you think you personally did compared to your peers when you were an undergraduate student that helped you become who you are today, or maybe form these interests in research on fungal pathogens that you have today?
Dr. Xu: I don't think my background is really that different from a lot of people.
I was introduced into science at a very late age coming from rural China. There's almost no science education when I was younger. After I got in the university, I started reading things and become more and more interested in a variety of things. And I'm still interested in very broadly a variety of things from agriculture technology to food science, to epidemiology, to infectious diseases, and human evolution itself. I have very broad interests. I think that might have contributed to some of those, if you look at my publication lists, very broad organisms that I work with and very broader disciplines that I work with. I think it's maybe what you can call it more fashionable term is interdisciplinary. That I like to explore things, even to this day, whatever attracts my attention, I'm saying, ‘oh, that sounds interesting I'm wondering what we could do about it from my perspective, what we could add to it.’
Yumnah Jafri: I see. So just really pursuing your genuine interests in a variety of scientific fields. You briefly mentioned this, but do you have any specific advice you want to give students, listening to this show right now and who are interested in pursuing research, either in general or at Xu Lab along alongside you?
Dr. Xu: Research is really fascinating. I think McMaster really positions itself very well. Students come to McMaster really have a huge opportunity. We are research-intensive university, faculty are generally very well-funded, we have a very active graduate student population on campus that can help guide the students…So, I think students should take advantage of the research opportunities. The general advice I would give is talk to the faculty, talk to the professors, ask them what their researchers is and their research activities are, and just explore the opportunities. One fun fact, based on my observation, is that professors generally are eager to talk to the students about their research. We will not be burdened by any questions relating to our research. Basically, if you find something that might interest you or you have a question about the subject that you think somebody on campus might be able to help you, connect with them, and most of the time, they'll be very happy to try to find the answer or to try to answer your question or help you find the answer for your question.
For my lab, I typically take students in based on their interests. As a faculty in biology, I'm primarily responsible for the students in our program, right? So, whoever expressed the interest in mycology wanted to do a thesis in my lab, I typically look at them very favorably. It’s typically first come, first serve if they wanted to research in my lab for their thesis.
Yumnah Jafri: Reaching out to you early on in the semester rather than later, right?
Dr. Xu: We have forms that you could fill. If you think that your research interest aligns with mine, you can indicate my name. I will probably give you an interview and see whether we have something that overlaps, there's something that we can provide to achieve your interest to help you solve your problem or solve your curiosity.
Yumnah Jafri: For a final question, Dr. Xu, what do you think is the most interesting fungal pathogen? This could be in terms of appearance, you know, structure, reproduction, just whatever you thought was really quite interesting to you.
Dr. Xu: That's actually a very tough one. For myself, I think Cryptococcus is very interesting, and still is. So, it has two big species complex, with each species complex they have divergent lineages. Those lineages were probably diverged from each other because of historical reasons. Biogeographic separation, for example. Ever since humans involved, we start spreading and human created a lot of other things that are also spreading with us. For example, pigeons and trees. We are transplanting trees from one place part out of the world to another part of the world. Cryptococcus is found in a lot of different ecological niches. When we started moving things around, for example, passenger pigeons about a hundred years ago, and eucalyptus tree that is a native host for Cryptococcus, then we start transporting those pathogens to different parts of the world as well. And that created opportunities for the different lineages to hybridize with each other. We have seen those signatures over those hybridization based on DNA sequences of the current strands. So, how do historical separation and contemporary gene flow, those two factors come together, influence the pathogen and influence their virulence, their drug assistance stress resistance, etc. That would have a significant implication for the evolution in the public health.
As I was mentioning that 20% of the deaths from AIDS was due to Cryptococcus meningitis. And this fungus, this is a preferred site. The central nervous system has this affiliation to get into the brain and grow over there. Most of the routes of transmission is through the respiratory system, we breathe, lodges onto the lung, and then they find the opportunity to germinate and then penetrate into the bloodstream, and then from the bloodstream they’ll cross the blood brain barrier and then get into the lung to cause meningitis, but the brain is the preferred site where the disease is most deadly. Just a lot of really interesting features of how they become high affinity for the central nervous system. It's not really very well known. And how this hybridization among divergent lineages impacts those behavior. It's not really very well understood.
Yumnah Jafri: So maybe one of our listeners from our talk here today might in the future, work with you to help answer some of these questions about Cryptococcus, right?
Dr. Xu: Well, Candida auris is another example. Actually, all four-priority fungal pathogen have a very, very interesting aspects. Candida auris has emerged only about 10 years ago, and now we identified has at least five different lineages that are evolutionary divergent from each other, at least a few hundred years, maybe over thousands of years, diverging from each other at different locations. Now, suddenly, they all emerge as public health threat. This fungus is resistant to multiple drugs and resistant to automatic stress, high salt concentration, like 10% salt. It's not going to kill them. And high temperature, like our fever would not kill them, unlike many of the other fungal pathogens. They would not. This one can easily grow at 41 degrees. It's a high fever…where did originate and what's driven their emergence. We don't know.
Yumnah Jafri: Those are some pressing questions and incredibly, incredibly concerning aspects of this pathogen. Thank you so much Dr. Xu and that's it for this week of SciSection. Make sure you check out our podcast available on global platforms for our latest interviews.