Investigating Global Infectious Disease Threats with Egon Ozer, MD, PhD

• Ozer traveled the world as a young child in a military family. Early exposure to international culture and German schooling helped shape his global perspective in medicine and research.

• His dual background in infectious diseases and molecular biology informs his approach to global health challenges allowing him to better understand how to control the spread and development of infectious diseases and apply them to clinical solutions.

• His PhD research focused on how pseudomonas aeruginosa communitate,  and studied how to interrupt that communication between so that they're no longer able to organize and form biofilms  with either in patients or on surfaces.

• During COVID-19, Ozer shifted from bacterial genomics to viral genomics, helping map SARS-CoV-2 evolution locally in Chicago and globally in low-resource regions.

• The growing crisis of  antimicrobial resistance is driven by antibiotic overuse, agricultural practices, and slow development of new therapeutics.

• Through the Center for Pathogen Genomics and Microbial Evolution, Ozer’s team tracks resistant bacteria and fungi worldwide, revealing regional differences and surveillance gaps.

• He runs a CDC-funded project in Pakistan identifying a previously unrecognized fungal pathogen causing deadly infant infections. 

• Ozer stresses that capacity must be built in all areas around the world to combat the looming threats he and his team are addressing.

[00:00:00] Dr. Rob Murphy: Welcome to the Explore Global Health Podcast. I'm Dr. Rob Murphy, executive director of the Havey Institute for Global Health here at Northwestern University Feinberg School of Medicine. My guest today, Dr. Egon Ozer, is a leader here at the Havey Institute for Global Health, where he is Director of the Center for Pathogen Genomics and Microbial Evolution, helping researchers at Northwestern and around the world use genome sequencing to track emerging diseases and prepare for infectious threats. His work has played a pivotal role in tracking COVID-19 variants, and investigating the ongoing problem of antibiotic resistant infections around the world. We welcome him to the show today to talk about his career in global health and the cutting edge research his team is leading here in Chicago, Pakistan, Peru, Bolivia, Nigeria, and beyond. Welcome, Egon.

[00:00:59] Dr. Egon Ozer: Thanks so much.

[00:00:59] Dr. Rob Murphy: Your academic career started in Minnesota at St. Cloud University. Where you studied biotechnology and then you completed the medical science training program at the University of Iowa where you earned your MD and PhD. Did you grow up here in the Midwest? And was there anything in particular that led you down the path to becoming a physician scientist?

[00:01:22] Dr. Egon Ozer: I am actually not a native mid-Westerner. I grew up kind of around the world. My father was in the army and so we traveled extensively for his work. So I've lived in Germany. I've lived in Texas and Maryland. Never actually got stationed in the Midwest, but most recently my family had ended up in Alaska and then after I finished high school there, I was looking for biotechnology programs, that was a major interest of mine. And so St. Cloud State University had one of the better ones and uh, decided to go there. And I've been in the Midwest ever since.

[00:01:54] Dr. Rob Murphy: You've been around the world, an army brat turned a physician scientist. Where did you live in Germany, by the way?

[00:01:59] Dr. Egon Ozer: I lived most recently in Stuttgart or near Stuttgart. I lived in a small town by the name of Leonberg. actually went to German schools there. And so that was maybe sort of the beginning of my international experience was that I lived off base and went to the local German schools from about fourth grade and through eighth grade and learned the language and had local friends

[00:02:19] Dr. Rob Murphy: That's great. How's your German?

[00:02:20] Dr. Egon Ozer: It's not as good as it used to be. I was recently traveling and spent some time in Germany with my family on vacation, and every time I spoke to somebody in Germany and German, they would respond to me in English. So I think that, I don't know what that says about my German skills.

[00:02:34] Dr. Rob Murphy: Yeah, I think that's what happens all around Europe these days. Speaking different languages. I lived in Germany myself. I did a sabbatical and lived in Berlin. We have a couple things in common I didn't even know about.

[00:02:44] Dr. Egon Ozer: How's your German?

[00:02:45] Dr. Rob Murphy: SCH Select. For those of you who don't know German, it means bad. How did that dual perspective as a physician and a molecular biologist shaped the way you approach global health today?

[00:02:57] Dr. Egon Ozer: Yeah, that's a good question. So I, you know, starting with the medical side, global health is definitely been an important part of my training and my career. Especially as an infectious disease specialist, given the outsized importance of infectious diseases around the world in terms of causing morbidity and mortality among patients and individuals it's a big public health problem, in infectious diseases and in multiple places around the world. And so that certainly informed my global health perspective. But from the PhD side, from the molecular biology part of my training and research I saw the problems of global health and wanted to apply some of my research training to those as well, especially in molecular biology and genomics try to better answer some of these questions about how to control infectious diseases, how to track infectious diseases and to better understand how they develop and how they spread so that we can apply those to clinical solutions.

[00:03:51] Dr. Rob Murphy: How did you work your infectious disease training in with your PhD.?

[00:03:56] Dr. Egon Ozer: My PhD work was always involved in clinical aspects of molecular biology. My PhD work was studying a bacterium called pseudomonas aeruginosa. It's a commonly found bacteria. It's actually environmental. It's found in water sources and in soil and doesn't tend to cause a lot of clinical problems until something compromises your immune system, in that you get chemotherapy for cancer or you receive a transplant. Or even just being sick in the hospital for another reason and requiring some sort of line to be placed or a breathing tube to be placed, you become at a higher risk for this infection by this organism. And so I studied that organism for my PhD work and I specifically was interested in how bacteria talk to each other. How pseudomonas communicate with each other to organize their behavior, to do different things when they're in large groups than when they're individual bacteria floating around. And so specifically I was interested and studied how to interrupt that communication between bacteria so that they're no longer able to organize and form biofilms with either in patients or on surfaces. And also how they can use that activity to become more resistant to antibiotics. So my PhD work was very heavily involved in infectious disease.

[00:05:09] Dr. Rob Murphy: So was that an integrated program at the University of Iowa?

[00:05:13] Dr. Egon Ozer: Yeah, that was the medical scientist training program at the University of Iowa. And so I did my two years of clinical didactic training a couple of rotations and then went right into the lab. And did my graduate studies and then my graduate research, defended my thesis and then went back to complete my last about year and a half of clinical rotations to complete medical school. It was an integrated program that throughout the medical training there was connections to research, and throughout the research training there was connections to the medical side. They were never completely separate.

[00:05:44] Dr. Rob Murphy: For those listening who may not be familiar with the field, explain pathogen genomics. The term and the field. And why has it become such a critical tool for global disease surveillance?

[00:05:57] Dr. Egon Ozer: Sure. I mean, sort of taking it one word at a time. Pathogen refers to organisms, especially microorganisms that cause infections. Primarily I'm interested in infections in humans, but pathogens can refer to organisms that cause infections and animals or plants as well. And so when I say organisms, this can include any kinds of microorganisms including, bacteria, viruses, fungi even some parasites as well. These are all classified under pathogens. And then for genomics refers to the study of the genome. And so the genome is the complete genetic makeup of an organism. So all of the genes and all of the genetic material that constitutes the genetic instructions that an organism contains within its cell or cells is its genome. And so it's not, rather than just looking at individual genes that may control one aspect of an organism's behavior or development genomics is focused on looking at the entire structure of the genome, all of the genes together, as well as other components of the organism's genetic code. To understand how they develop different characteristics and how they transmit and how they interact with each other using the field of genomics.

[00:07:13] Dr. Rob Murphy: When I first met you on the faculty here I was very impressed that we had a young scientist who's working in bacteria, especially pseudomonas, which can be such a horrible problem in hospitalized immunocompromised patients. And then all of a sudden there was the COVID-19 pandemic. So I came from the HIV side of our division, and you came from the bacterial side of our division, and we both collided in the Covid 19 pandemic.

[00:07:40] Dr. Egon Ozer: As we all did, yes. In some way or another.

[00:07:43] Dr. Rob Murphy: I was very happy to get to know you and work with you a little bit more because I don't work with pseudomonas at all. But the COVID-19 pandemic put pathogen genomics in the spotlight, and your work was often headline news. How did that experience of the COVID-19 pandemic shape your research and influence your global collaborations?

[00:08:03] Dr. Egon Ozer: Yeah, it definitely was an important factor in sort of the development and the, even just the creation of the Center for Pathogen Genomics and microbial evolution. A lot of that did come out of the COVID 19 pandemic. As you said my research and my training has primarily been in bacteria, which I think most listeners of this program will know COVID-19 is not a bacterium. It's a virus. And so viruses like, you know, our microorganisms like bacteria, but they've got a lot of differences in their biology and also in their genomes. So the way I came into the COVID-19 pandemic was by trying to apply the skills and the techniques that I developed and used for studying bacterial genomics and in collaboration with some fantastic virologists here at Northwestern, tried to apply those techniques and those skills to viral genomes as well. And what we together as a group did was to determine the genomic content and genomic makeup of COVID-19 viruses or sars CoV2 viruses here in first in the Chicago area and to understand how it was evolving and transmitting throughout the Chicago region. And then further expanding as the COVID-19 pandemic went on to better understand SARS CoV2 evolution and variation in parts of the world that had not been as fortunate as the US or as Europe. In terms of being able to have the access to resources to understand and to study the SARS CoV2 or viruses that were circulating within their own populations. And

in Nigeria with our collaborators there, we were able to identify a new variant of SARS CoV2 that had not previously been described. Just by being able to look in a place that didn't normally have access to those resources. And we've done similar work in Peru and in Bolivia as well to look at SARS CoV2. So the COVID-19 pandemic really did highlight the importance of pathogen genomics for understanding how viruses evolve, how they transmit, and understanding the characteristics of the viruses that may contribute to them not responding as well to vaccines or to therapeutics. And that's been able to then be applied now to even more different types of pathogens beyond just sars CoV2.

A similar kind of, phenomena happened with me and many other people too that worked exclusively with HIV, we all just flipped right over and started working on COVID and it was we, our focus was more in the diagnostics area and, but it was the same HIV people everywhere and it was the same network. Yeah, there were a lot of scientists around the world who wanted to be able to contribute and use their skills that they'd honed either in virology or other aspects of science to try to tackle this global problem. And I think it really pointed to the and highlighted the collaborative nature of science around the world and brought down a lot of silos. I'm really hoping that continues going forward.

[00:10:53] Dr. Rob Murphy: There's another global health crisis that you are working on, and that is often called a silent pandemic. And what I'm referring to is antimicrobial resistance. Can you explain this worldwide crisis? Is it really a worldwide crisis? And what is fueling it and what's being done about it?

[00:11:12] Dr. Egon Ozer: Sure. So antimicrobial resistance refers to the characteristics of bacteria, viruses, fungi, anything that requires an antimicrobial medication where those organisms are no longer killed by the drugs or medications or treatments that used to be able to be used to kill those organisms. And so there's a number of different Characteristics or pathways whereby microorganisms develop resistance to these medications and treatments. And, but at the end of the day the, effect of that is that it becomes harder to treat infections and it's become such that infections that used to be quite easy to treat, you know, that medications would work very effectively against them, that they could be given as pills potentially that now they're becoming more infections that are more difficult to treat. They require medications that have more side effects or medications that can only be given through intravenously or in a hospital or becoming more expensive. And so this is a growing problem and it is a growing global problem. Not just the United States, but around the world. This is an issue that is being addressed and faced by communities around the world. Some of the drivers for antimicrobial resistance include overuse of antibiotics. Antibiotics can be over-prescribed, you know, there can be viral infections that physicians are prescribing antibiotics for, so they're trying to give medications used to treat bacteria for an infection is caused by a virus. And not only does that medication not actually treat the infection, but it can start to induce resistance in organisms that normally live within our bodies. And then when an infection occurs with one of those organisms, it's harder to treat. Also the use of antibiotics in agriculture it has been a longstanding practice. This used to be in the United States is now not used in the United States anymore, but certainly around the world antibiotics are used to fatten up livestock more quickly to make, other farm animals more healthy, but the result of that is that the organisms that they're colonized with or that they come in contact with then can develop resistance as well. And so this is an increasing problem. And there's a number of ways that this is trying to be addressed. One of them I mentioned was to try to get antibiotics out of use in agriculture other than when they're especially needed to actually treat an actual infection to try to improve prescribing practices so that antibiotics aren't prescribed when they're not needed. And then when they are prescribed, they're prescribed for just long enough to treat the infection and not longer. Again, all these things to try to prevent the development of resistance within organisms that otherwise wouldn't have it. Other things that are being worked on are development of new therapeutics that are more effective against antimicrobial resistant organisms. Unfortunately, this is one of the slower aspects of the process this requires pharmaceutical companies to invest in antimicrobials. And that sometimes can be a difficult investment choice given that these antibiotics are then used as little as possible to try to prevent resistance from developing to them. And so there have been government initiatives to try to support the development of sort of orphan antimicrobials that have had mixed success around the world.

[00:14:17] Dr. Rob Murphy: I know the WHO just recently released a report on worldwide bacterial resistance. It should be known that the United States has left the sphere, the WHO. But they're continuing on and they collect data from over a hundred countries. And some of the global data is really quite frightening. One in six laboratories confirmed common bacterial infections are resistant to the antibiotics. Urinary tract infections is one in three. I mean, this is definitely going in a very scary direction. Are, are you in agreement with, all that information?

[00:14:48] Dr. Egon Ozer: Yeah. It's terrifying. The danger is that we get to a point where infections that used to be survivable become fatal again. Used to be that bacterial meningitis was a hundred percent, almost a hundred percent fatal in the pre antibiotic era, pneumonia was upwards of 75 to 80% fatal in the pre antibiotic era. Now it's far less than that with antibiotics, but we could envision a world where we end up back at that spot where none of the antibiotics that we have are effective to treat these infections and things that should be survivable, become fatal again.

[00:15:20] Dr. Rob Murphy: What are you learning from your work through the Center for Pathogen Genomics and Microbial Evolution of which you're the founding director. What are you learning about the tracking of resistant bacteria and fungi uh, the different microorganisms across the reasons of the world? I know you're working in Asia, South America, North America, Africa, what's tying it all together and what are the things we can learn from working abroad?

[00:15:46] Dr. Egon Ozer: one of the major issues remains a lack of equity among resources to study genomics and to study the genomic basis for antimicrobial resistance. You know, we've seen this happen where genes or factors that cause antibiotic resistance emerge in one part of the world. And then these are sort of under-recognized, or they are very slow to be recognized because surveillance for these, especially for the development of new genes, is not universal. And so then these start to become more prevalent within the regions that they're first found and then spread globally such that they become not just a local problem that could be controlled, but a global problem that is then sort of outta control. And what we're finding with our partners in, as you mentioned in South Asia, in South America and in Africa, is that to sort of access to these resources that we take for granted in the US or in Europe are not as accessible in these regions. And so a lot of times we just don't really know what factors are causing resistance within the organisms that are antimicrobial resistant in these regions. And it's important to know because, and as I mentioned, sometimes we do see the emergence of new resistance factors and we see them spread across regions. And so early detection and really understanding of the transmission of genes or factors that cause resistance within a region can lead to earlier interventions to try to interrupt that transmission. To try to slow it down and kind of give the world a chance to stop it in its tracks. But we are finding that as we look in these different regions at the genetic information that is available, that the factors that cause resistance can be very different from one part of the world to the next. And so understanding that can also contribute to understanding or better formulating how to treat those infections within those regions.

[00:17:32] Dr. Rob Murphy: Your team's work in Pakistan has already been instrumental in identifying a new fungal infection that causes serious blood infections, mostly in infants throughout Pakistan. How have doctors and public officials there responded to your findings? And could you tell us just a little bit about the whole project?

[00:17:49] Dr. Egon Ozer: Sure. I'll start with the project. So with our collaborators at Aga Khan University in Karachi, Pakistan, we have an ongoing project funded by the CDC to examine antifungal resistant candida infections. Candida is a species of yeast that certain species of it can cause serious infections around the world. And so there is a species of Candida called Candida auris that emerged, about little less than 20 years ago at this point, and is spread around the world. That can cause very severe antifungal resistant infections in the lungs or in the urine, or in wounds, in some cases. And like I said, it can be very difficult to treat because a lot of these infections are resistant to most antifungals. And so this project in Pakistan was to better understand the transmission of Candida auris and other antifungal resistant Candida within the region within the country by using genomics to sequence the genomes of these fungi, compare them to each other and to understand how closely related they are and whether we can see relationships of how these organisms spread either within the hospital or within the region or within the country. And so as part of this project we sequenced other fungal infections mostly other antifungal resistant candida. But our colleagues there noted that there had been a big increase in cases of infections with a certain kind of fungal organism that was being identified as a Candida Lusitaniae. Candida Lusitaniae is a pathogen, it can cause infections. But what they were noting was that cases had increased very rapidly from one year to the next. And that they were primarily infecting young infants, under the age of four weeks of age, that it was causing infections in the bloodstream of these children. And they were becoming very sick and many of them were dying. And so we used the infrastructure for sequencing that we had set up with our colleagues there to sequence these Candida Lusitaniae again, to mostly try to understand whether they were being transmitted from patient to patient or whether we could find a particular point source where these infections were coming from. And as part of that process, by sequencing the entire genome, we were able to determine that what was being identified as Candida Lusitaniae actually was a different species. The biochemical tests that the clinical microbiologists were using didn't have a way to identify the species that it actually was. And so we're misidentifying it as a different species. And so we actually found that the organism was a different species of yeast called Scheffersomyces spartinae. And when we looked in the literature to find other reports of infections with this organism, there were none. The only reports that had ever been published about Scheffersomyces spartinae were about how it was found in the environment. And it could be found in some industrial applications, but no one had ever reported a single infection with this organism. And then now we were identifying well over eighty, and by the time we were done with our initial study, there had been well over a hundred infections in young children with this organism. So we were able to identify the complete genome sequence of this organism and actually show that the organisms the Scheffersomyces spartinae that were causing infections in Karachi and in southern Pakistan were genetically distinct from those that were causing infections in the northern part of the country. And so there were actually regional versions or variants of the organism that were causing infections in different parts of the country. And like I said, those infections were many of them were severe. They were, you know, children who were becoming very ill ending up in the local ICUs or dying in some cases. As a result of this study, there's been an increased recognition of these kinds of infections, an increased evaluation by the hospitals in the region and around the country to look for these particular kinds of infections and try to identify them early by some of their genetic characteristics or the biochemical characteristics and to try to treat these early to try to prevent infections. But that study is still ongoing, the work is still ongoing, the transmission rate has continued onward and continues to increase year over year. It is still a growing problem.

[00:21:41] Dr. Rob Murphy: Your team also has helped develop genomic sequencing infrastructure, not only in Pakistan, but Peru, Bolivia, Nigeria, and any other low and middle income countries. Why is it important to build capacity for actually the mechanical part of pathogen genomics in these countries?

[00:21:58] Dr. Egon Ozer: It's important because this capacity is, for one thing , too small to cover the entire world. Just in the large sequencing centers that are found in the US and in Europe. There's so many infections and especially with growing antimicrobial resistance it's just too much for centralized sequencing and operations and genomics operations to really get their arms around all of the surveillance that needs to be done. And so it's important to build that capacity in the areas where the infections are actually occurring so that data can be received much more quickly rather than trying to collect specimens and batch 'em together and send them to us here in the US or somewhere else. Wait for the sequencing to be done, wait for the analysis to be done, and then shared with back with the country where the infections actually occurred. By building local capacity then it can go directly even especially in small batches of going from identifying an infection to performing the sequencing and understanding what the genomic determinants of that resistance or other characteristics of the organism are without having to rely on outside partners to do it. In a lot of cases, the local clinicians and public health experts have a better sense of what the most important infections in the region are. And so they can then use the capacity that is built to do the genomic sequencing, to do their own analyses to identify the organisms that are causing the most severe or the most concerning infections in those regions to quickly do the sequencing of those. And to be able to identify transmission patterns, to be able to see whether there's a particular, you know, single source for an infection or whether there's transmission that is ongoing within a community. And whether that the infections that they're seeing in that community represent one type of infection or whether there's infections coming in from other parts of the country or other parts of the world, they can do that much more readily, quickly, and much more effectively than relying on outside sequencing centers and analysis in the US or elsewhere. So it's very important that there's local capacity so that there's local determination and local treatment and assessment of these infections.

[00:24:04] Dr. Rob Murphy: Absolutely. We agree completely and our whole focus over the last really two decades is just moving the capacity to the places where we're working and the whole original concept of taking everything back here, running it in a big centralized lab, those days are really over.

[00:24:19] Dr. Egon Ozer: They need to be, and that's one of the things we're really focusing on, is just trying to build capacity and not just equipment, you know, not just computers and sequencers and PCR machines that's one thing. But really even just doing the analysis of this genomic data that you know, some locations actually already have those sequencers and they do have that, you know, capacity in terms of a lab but for doing the actual analysis, for understanding how to analyze the data, to apply it to local problems, that's one big thing that we're very focused on trying to teach through workshops that we're conducting around the world to build bioinformatic and computational analysis capacity in these sites.

[00:24:56] Dr. Rob Murphy: The Center for Pathogen Genomics and Microbial Evolution here at the Havey Institute is nearing its five year anniversary. What's next for the center? Are there any new technologies, partnerships or research directions that you're most excited about as you look for the next five years?

[00:25:12] Dr. Egon Ozer: Absolutely. Yeah. We have continued to build our collaborations around the world. We've mentioned several of them, and we only want to continue to build partnerships and develop collaborators around the world in pathogen genomics. So that will continue going forward. Most recently we received a very generous gift to fund a pathogen genomics and antimicrobial resistance surveillance program. And so that is something that is just getting off the ground now. And over the next five years, we're looking to build, local capacity in four different sites, at least to begin with, around the world to perform genomic surveillance and genomic sequencing of antimicrobial resistant bacteria, especially in places that have been, understudied where we don't really know much about what the mechanisms of resistance are, transmission of resistance where local capacity for genomic surveillance of not just antimicrobial resistant infections, but any pathogens is relatively limited. And we're looking to build that capacity over the next five years and to really contribute to a global understanding of the factors that lead to development of resistance in certain bacteria. Especially within these sites. But like I said, to use that to build a global network for surveillance to better understand on a global scale how resistance is developing, how it's transmitting and how it's emerging and in places that have traditionally not had the capacity to do so.

[00:26:31] Dr. Rob Murphy: One final question, Egon, that I ask everyone that comes on this podcast, what advice do you have for young people who are just now embarking or wanting to embark on a career in global health?

[00:26:43] Dr. Egon Ozer: I would say one of the most important things is to find the people that are already working in the field and learn from them. Regardless of what sort of aspect of global health that you're interested in, whether it's clinical practice whether it's public health policy development or research there are amazing resources that are available to you to partner with those that have expertise, have experience, and have the connections in global health to allow you to apply your interests and your passion on a global stage. I think the resources that we have here at the Havey Institute for Global Health are world class and I think are very accessible and available for individuals that have an interest to reach out to and to learn more about the work that we do and how we became involved in it. But I do think having that connection, having those resources to just sort of, start to even learn about what the problems are and how they might be addressed I think is a huge part of an entry into the world of global health.

Egon. Thank you so much for sharing your insights with us and explaining all the important work that you're doing, Thanks so much. It's been great talking to you.

[00:27:50] Dr. Rob Murphy: Follow us on Apple Podcasts or wherever you listen to podcasts, to hear the latest episodes and join our community that is dedicated to making a lasting positive impact on global health.