The most common cause of hospital-acquired pneumonia in the United States is a bacteria that increasingly thwarts standard treatments. Such antibiotic-resistant bacterial infections can be lethal, particularly for people receiving inpatient care. Speeding both the detection of these superbug infections and selection of their best treatment could save lives, the goal of XSeed Award winner Andras Fiser, PhD.
Fiser, Professor in the Department of Systems & Computational Biology and the Department of Biochemistry of Einstein College of Medicine, is spearheading research with two partner labs to address antibiotic-resistant bacterial infections. They are investigating how genome sequencing data and tools, such as a hospital lab’s mass spectrometry machine, might yield life-saving accuracy and efficiencies to address the growing public health concern that antibiotic-resistant bacteria pose to vulnerable patients in hospitals globally.
This conversation has been edited for length and clarity.
Cure: Before we talk about the critical work that won you an XSeed Award, let’s start from your early days: What was the spark that led to you becoming a scientist?
Fiser: I'm from Hungary originally. We had a TV program every Friday about the latest scientific discoveries in the world, and as a child I was glued to it. It was about everything from exploration in Alaska to deep sea diving to going into space. I told my parents I wanted to do something like that.
As I grew up, I was more and more interested in sciences and thought I wanted to be a medical doctor. My chemistry teacher told me to go into life sciences instead. She said, “You don't want to see sick people every day. You want to dig into the problem, so you should be a scientist.” I listened to her, and I'm very happy that I did.
Cure: Did you pursue infectious diseases?
Fiser: In Eastern Europe, we have only very big disciplines, like mathematics, physics, geography, biology, or chemistry. I went into chemistry because it contained everything from biology to physics to biomedicine. After I got a master's degree in chemistry, I went to work in academia, in the Institute of Enzymology, which was molecular structure-oriented research.
Then I moved to the US and went to Rockefeller University, which is very focused on the molecular basis of disease. I was always a basic science-oriented person, and my focus was always on what happens on the very, very detailed microscopic level.
Understanding on the molecular level what goes wrong in the system when someone gets sick — whether it’s cancer, infectious disease, inflammatory disease, any kind of disease — that’s what motivates me.
Cure: Tell us about the research you’re currently working on.
Fiser: The public knows about antibiotic resistance, but what they may not know is there are some bacteria that are even more threatening than others because of the high mortality rate, such as Klebsiella pneumoniae. It’s a commonly found bacterium and certain strains of it can turn into “superbugs” by carrying antibiotic resistant genes. They can give you pneumonia and cause other serious problems, frequently leading to death. Drug-resistant Klebsiella pneumoniae is a particularly deadly and unaddressed medical problem of infectious disease.
Cure: Who does Klebsiella mostly affect?
Fiser: Klebsiella infection is actually very rare — healthy people almost never get it. It typically appears in a hospital environment. These bacteria attack the lungs of elderly people who are bedridden where let’s say, someone has had a surgery, and you have open wounds that are healing and the bacteria gets through. These patients often have a compromised immune system, and since there is no real treatment, the infection just overtakes them.
The current situation is the infected patient is given an antibiotic, but if they don't respond, the clinician takes a blood sample and sends it to the lab. In the lab, they culture the bacteria from the blood with different antibiotics to see which one will respond and kill the bacteria. This process can take two or three days. If they find an antibiotic that works, they can go back to the clinic and suggest which treatment to use — that is, if the patient is still alive.
Sometimes when the doctor sees there is no response to a standard treatment, they immediately throw the most advanced antibiotics possible at the patient and hope for the best. But unfortunately, that often doesn't work.
Cure: How quickly is the threat growing?
Fiser: The first detection of this disease in the U.S. was in 2001. And within 10 years, it became endemic. It's now found in every hospital in New York City and in the U.S. It's spreading very fast.
It's one of the major goals of NIH to address these kinds of fast-spreading antibiotic-resistant infectious diseases. Bacteria are fundamentally responsive to penicillin-like treatments, but because of the widespread use of antibiotics, some bacteria acquire plasmids, which contain enzymes that will chew up and kill penicillin and survive the penicillin treatment. These are the antibiotic-resistant strains.
Over time Klebsiella developed antibiotic resistance even against the latest and most advanced generation of antibiotics, the carbapenems. There are different strains of Klebsiella and not every single Klebsiella infection is drug resistant, but because of evolutionary selection, these strains that are drug resistant are occurring more and more frequently.
Cure: How is your lab, along with your two partner labs, addressing the problem?
Fiser: A few years ago, we asked ourselves: How can we establish a methodology that can quickly detect if an infection is resistant to standard treatment? And how can we identify the right treatment for the patient?
We started with the two goals of shrinking the wait period to identify problematic cases, and identifying drugs or drug combinations that can treat patients. We have a huge number of antibiotics with different mechanisms, and what we found in our research is that sometimes, single antibiotics will be ineffective against drug-resistant Klebsiella, but drug combinations can be effective. Sometimes one of them will block the resistant genes in the bacteria while another drug will kill it.
Cure: How is the research conducted?
Fiser: What we do is we take blood samples that contain the bacteria from patients, then we add different antibiotics to each drop of blood. Using a mass spectrometry machine, you can detect which antibiotics or antibiotic drug combinations will be effective in a single minute.
If there is a drug-resistant gene producing an enzyme that destroys the antibiotics, you will not see the presence of the drug anymore on the mass spec analysis, because the bacteria will have chewed it up and destroyed it. If the bacteria are unable to chew it up and destroy it, the drug will be present in some concentration on the mass spec analysis.
After you culture the blood samples with the antibiotics, the readout will tell you which one is working, and the doctor can administer that to the patient. Essentially the longest time in our process is to get the sample to the mass spec machine — meanwhile the current protocol takes precious days, where the patient might not even survive that period.
Cure: Let’s talk about the XSeed Award. How did the award help you get where you are today?
Fiser: We’d had this idea for a few years, but initially we had no funding, so we were never able to do anything. Then we were given the XSeed Award and the funding was enough to pay a technician to do the experiments, for genome sequencing data, and for the chemicals we use in growing the bacteria and preparing the samples.
We’re now preparing all the data that we were able to obtain for a grant to the NIH to continue our work.
Thanks to the XSeed Award, we have much more than a concept — we have real data. The XSeed judges recognized the possible impact of this project, and we’re at the stage when we hope we can get a multi-year grant.
Cure: What's the timeline for when you think you might be able to achieve your goals of reducing the time of resistance detection, and identifying the right antibiotic treatment?
Fiser: We are doing all these experiments with a large sample size and with a variety of antibiotics. We have a lot of data we’re in the process of analyzing. We need to work out the protocol to detect resistance, and the currently unknown drug combinations that should go into practice to attack drug resistant infections in the clinic.
So, the timeline is a bit unpredictable. It's a bottleneck that we must overcome, and once we overcome it, we will suddenly be able to answer all these questions.
The feasibility of this method is very high because there is a mass spectrometry machine in every hospital nowadays. So if we have a protocol to provide, it can be implemented directly in any hospital.
And there is a strong interest from hospitals — they tell us that they have these resistant samples in patients all the time, and it's spreading. And it’s not just Klebsiella — drug resistance is a widespread phenomenon. I'm hearing more and more from the clinicians that we should focus on E. coli because drug-resistant E. coli is found more and more frequently in the hospital.
Cure: It truly is so needed, and it’s encouraging to know there are three labs working so diligently together to combat this growing problem. Shifting to a final question: Do you feel that as a society, the US gives science the respect it deserves?
Fiser: I do think the US is much better than many other countries, including European countries. There is no other country or organization that spends as much money on science as the NIH.
The other question though is: “Is science education at right level in the US?” I think that's a problem. People often use science for political purposes and ridicule it — they criticize spending money on things that don't benefit people immediately. I believe the only way to overcome that is education.
Now in its fourth year, the XSeed Award program provides up to $250,000 grants to New York City minority- and women-led life science and healthcare startups working on novel preclinical drug development projects. Winning teams also join the ecosystem of Cure.®, a healthcare innovation campus in New York City. The teams receive peer-learning and office hours with investors, entrepreneurs, and business experts. Learn more.