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Can We Prevent a Future Without Effective Antibiotics Through Better Monitoring?

Can We Prevent a Future Without Effective Antibiotics Through Better Monitoring?

Antimicrobial resistance (AMR) represents one of the most pressing challenges in global health today, as pathogens evolve to outsmart our most effective treatments. AMR occurs when microorganisms like bacteria, viruses, fungi, and parasites develop the ability to resist the effects of drugs that once killed them or inhibited their growth.

In this interview, Windi Muziasari, CEO and founder of Resistomap, provides an in-depth look at how her company leverages biological technologies to monitor AMR. Windi explains why antibiotic resistance is becoming a major concern, details how and where resistance is spreading, and describes how Resistomap’s services help various sectors understand and control the spread of resistance. She also explores the broader implications of AMR on global health and the environment, as well as Resistomap’s vision for the future.

Supertrends: Why don't we start by explaining what you do at Resistomap?

W.M.: Yes, of course. At Resistomap, we offer a comprehensive, end-to-end service for environmental AMR monitoring. This means we monitor AMR in environmental samples, utilizing high-throughput profiling methods combined with the Resistomap platform. Essentially, we integrate molecular genetics and data science to deliver results quickly and cost-efficiently for customers who need data on antimicrobial resistance.

Supertrends: And you focus specifically on antibiotic resistance, right?

W.M.: Antibiotic resistance is a subset of AMR, which is an umbrella term covering the ability of microorganisms such as bacteria, viruses, fungi, and parasites to resist the effects of medications. However, most AMR concerns are related to bacteria. The main issue we're addressing is that antibiotics are becoming less effective against bacterial infections, which is why antibiotic resistance is often discussed under the broader topic of AMR. But yes, our main focus is on antibiotic resistance.

Supertrends: Could you also explain how bacteria become resistant to antibiotics?

W.M.: First, it's important to understand that antibiotics occur naturally in the environment, produced by certain bacteria and fungi. For bacteria that produce antibiotics, they must also have a resistance to them—otherwise, they would be killed by their own antibiotics. So, there are naturally resistant bacteria in the environment. Since 1928, when Alexander Fleming discovered penicillin, an antibiotic produced by fungi, we have been mass-producing antibiotics. This has caused naturally resistant bacteria in the environment to increase significantly.

The more we use antibiotics, especially heavily in humans and animals, the more these antibiotics end up in the environment. This results in higher concentrations of antibiotics in natural settings, which increases selection pressure on bacteria, causing more of them to become resistant. These resistance genes can be transferred between bacteria, which is why antibiotic resistance spreads. This is a major concern because all of these resistant bacteria can spread through the environment, particularly through wastewater. For example, antibiotics are heavily used in hospitals and animal farms, and waste from these places carries resistant bacteria into the environment. This is what we refer to as an 'AMR hotspot.'

Additionally, antibiotic manufacturing facilities are another source of resistant bacteria in wastewater. Most wastewater treatment facilities aren't designed to remove bacterial pollutants; they're usually focused on removing chemical pollutants. As a result, resistant bacteria end up spreading through water bodies and, eventually, into our food chain, reaching us even if we haven't used antibiotics ourselves. This makes understanding how bacteria become resistant crucial, not only in clinical settings where people or animals are treated with antibiotics but also in the broader environment.

At Resistomap, we think it's important to address not just the immediate need to treat patients infected with resistant bacteria but also to prevent the spread of these bacteria through the environment. This aspect is often overlooked because the focus tends to be on treating sick individuals or animals. However, preventing the spread is crucial to control AMR.

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Supertrends: If you had to summarize why we have this problem now, would you say it's because of the overuse of antibiotics in various settings?

W.M.: Yes, exactly. In the past, we weren't aware of the impacts of heavy antibiotic use. Antibiotics were often considered a 'magic medicine,' used for nearly any illness, sometimes without even checking if it was bacterial. This is still the case in some countries due to a lack of diagnostic technology. But now we see that the heavy use of antibiotics is a major driver of resistance. Besides the heavy use, the spread of resistant bacteria through water bodies has also recently been recognized as a significant issue by international organizations like the United Nations. And this isn't just a human issue; it's also a significant problem in agriculture, where antibiotics are heavily used in farming.

So, it's clear that both overuse and the environmental spread of resistant bacteria are driving the AMR crisis.

Supertrends: That makes a lot of sense. So how do you monitor the spread of antibiotic resistance? What methods do you use at Resistomap?

W.M.: We use molecular genetics methods because we study antibiotic-resistant bacteria in environmental samples. Unlike clinical or animal settings where bacteria can often be isolated and grown, most bacteria from environmental samples can't be cultured in a lab. Studies have shown that over 99% of bacteria from environmental samples cannot be grown in the laboratory. So, we use a method called environmental DNA (eDNA) technology.

Environmental DNA technology is becoming more common, not just for studying AMR but also for assessing biodiversity. We extract all the DNA from the environmental samples, which includes bacterial DNA, and then we measure specific genes using a technique called qPCR (quantitative polymerase chain reaction). You might be familiar with PCR from COVID-19 testing. We use a high-throughput qPCR system, called the SmartChip qPCR system, which allows us to perform up to 5,184 reactions at once. This system uses much smaller reaction volumes, which saves on DNA samples and reagents, making the process more cost-effective.

We use high-throughput qPCR because it provides quantification data, not just qualitative data. This is important because we want precise measurements. Given the large data sets generated, we also employ data science to automate the analysis, making the results easier to understand, especially for decision-makers who need actionable insights.

Besides high-throughput qPCR, another powerful method is metagenomics. This involves sequencing all the DNA in a sample, which provides a comprehensive overview of all the genes present, including resistance genes.

Metagenomics offers a detailed profile of AMR but does not provide quantification data, which is why we often complement it with high-throughput qPCR to get both the presence and the abundance of resistance genes. Other methods, like isolating bacteria directly from water samples for clinical analysis, are also used but tend to focus more on pathogens. It's important to know the different ways to monitor antibiotic resistance to choose the most appropriate method depending on the specific context and needs.

Supertrends: So, just to make sure I understood correctly: basically, you don't specifically monitor which bacteria are present in a sample but rather the antibiotic resistance genes. You could say that, for example, you discovered a resistance to certain antibiotics in a given sample.

W.M.: Yes, exactly. With the current technology, we can't determine which bacteria are carrying these genes unless we culture them and isolate the bacteria themselves. So, that's a limitation of using environmental DNA technology.

Supertrends: Is it possible for the same gene to be carried by two different strains of bacteria?

W.M.: Yes, that's exactly what I was mentioning earlier. One of the reasons antibiotic resistance is so concerning is that genes can be transferred between different bacteria through mobile genetic elements. Mobile elements like plasmids or transposons can carry these genes and move them from one bacterium to another.

Supertrends: So, this can happen between different species as well?

W.M.: Yes, it can occur between different species and even across different environments. For example, bacteria in soil, water, animals, or humans. This is one reason why, as I mentioned, when resistant bacteria are released into water, they can spread easily. The genes can transfer between bacteria and eventually make their way back to pathogens.

And then we can get infected with them. It's a scary thought. These resistant bacteria are already everywhere. As I mentioned, most wastewater treatment plants aren't designed to remove microbial pollution. Since we started using antibiotics about 60 or 70 years ago, most of these plants haven't been optimized to remove resistant bacteria—especially in low-resource settings where they might not even have treatment facilities. Imagine resistant bacteria from pathogens being released into our rivers every single day for many years. That's why many rivers in low- and middle-income countries—or even high-income countries lacking proper sanitation—are polluted with resistant bacteria. Then, we use this water for agriculture, animal husbandry, or even recreational activities like swimming. We're already surrounded by these microbes.

Supertrends: OK, so let's say someone uses your technology or services to find out how bad the spread is that their company or operation is causing. What actions can they take based on this monitoring? How does it help them?

W.M.: That's a great question. As I mentioned, we combine molecular genetic technology not just to identify that there is a problem but also to offer solutions. We are developing the Resistomap platform, which we will officially launch this September (2024) at the World Water Congress in Philadelphia. We're really excited about it.

Supertrends: Oh, that's great!

W.M.: Thank you. This platform won't just display complex lab results that you'd typically see in scientific papers. It will also provide users with the Antibiotic Resistance Genes Index. By indexing resistance genes, we make it easier for decision-makers to understand which regions need more attention. If the resistance index is high, it indicates more pollution or higher antibiotic use in that region.

Moreover, if you can identify specific types of resistance genes that are prevalent in a region, you can trace them back to potential sources, like hospitals using particular antibiotics more frequently. This resistance index is incredibly important for public health because it helps to identify antibiotic resistance at the population level, not just clinically, and to understand the extent of its spread in specific regions.

Additionally, our platform provides a comparative risk assessment score to determine the burden of antibiotic-resistant genes in the environment. This is useful for environmental health assessments, like ensuring that bathing or drinking water is safe. It also helps antibiotic manufacturers align with sustainable practices by assessing the risk factor associated with their wastewater, ensuring that it's properly treated before being released into the environment.

Another feature of our platform is process performance monitoring. This helps water utilities track how well their wastewater treatment plants are removing resistance genes. If they have multiple treatment plants, they can compare performance, figure out which ones are doing well, and apply best practices to the ones that aren't.

For health-related applications, this Antibiotic Resistance Genes Index is valuable for risk assessment and process performance evaluation. It can also be used to measure the effectiveness of interventions like vaccination campaigns. Vaccinations can reduce antibiotic use, but it's not always clear whether these campaigns are effective. We can measure this at the population level using wastewater samples to see the impact, not only in reducing antibiotic use but also in lowering AMR levels in the community. It's crucial to ensure antibiotics remain effective because if a population already carries resistant bacteria, antibiotics won't work when needed in healthcare settings. This is very important.

Supertrends: We’ve discussed it a bit already, but could you name the main sectors that could benefit from your company’s services?

W.M.: At the moment, our primary focus is on the water sector. In the EU, there is already a directive that requires urban wastewater treatment plants serving over 100,000 people to monitor antibiotic resistance. This directive has passed through the European Council and Parliament and should be implemented by 2027. That’s why now is the right time for us to ensure that every wastewater treatment plant in the EU serving over 100,000 people is prepared to monitor AMR. So, our main sector right now is water utilities, which can be municipalities or private sector actors that own urban wastewater treatment plants.

Our focus on the water sector is due to the fact that wastewater is a significant source of the spread of antibiotic resistant bacteria and its resistance genes. While soil can also harbor resistant bacteria, especially from manure used in agriculture, these tend to remain localized unless they are washed away by rain into water sources. Thus, tackling the issue at the water level is crucial.

But when we talk about the water sector, it’s not just limited to water utilities. It includes antibiotic manufacturers, food production industries, and any sector that is water-intensive—for example, the case of contaminated eye drops with resistant bacteria in the USA last year. The source of eye drops contamination can include water that’s polluted with resistant bacteria. So, it’s important to monitor antibiotic resistance throughout the production process, including in industries using large amounts of water.

Supertrends: So, essentially, almost any industry that involves water could be affected?

W.M.: Yes, exactly. However, without specific customer requests or regulations, industries may not be motivated to implement these measures. In many cases, industries are focused on cost-saving, and unless there’s a regulatory requirement or consumer demand, they may not prioritize this issue.

And if it's not regulated or demanded by consumers, the market for such measures may not develop as quickly as it could in the water utility sector, where regulations are more imminent.

Supertrends: I wanted to ask you about the challenges you face, both technological and in terms of market readiness and awareness. Could you elaborate on these challenges?

W.M.: Yes. The main challenges are primarily related to market readiness. Technologically, antibiotic resistance monitoring has been around for over 20 years, so the technology is quite mature. The challenge for us is more about market readiness.

Antibiotic resistance is a relatively new concept outside of clinical settings. In hospitals and veterinary practices, the issue is already well-established, and there’s clear demand for diagnostics and new antibiotics. However, in terms of broader environmental monitoring and prevention, the market is less prepared.

Our focus is on prevention—stopping the problem before it arises and ensuring that antibiotics remain effective and that we can safely use water for various purposes. This preventive approach can be challenging to sell because it's akin to insurance; people often only see the value of prevention when a problem actually occurs.

Supertrends: Yes, it’s difficult to convince people that 'nothing happening' means success.

W.M.: Exactly. The challenge is raising awareness, especially among decision-makers. Antibiotic resistance is a complex issue that requires a One Health approach, involving human health, animal health, and environmental science.

The difficulty lies in integrating these different fields to tackle the problem effectively. It’s a slow process because everyone is focused on their own areas. Ideally, we should have a more coordinated approach, similar to how the COVID-19 pandemic increased awareness of preventive measures.

We want to avoid waiting for a major outbreak of resistant bacteria to drive action. Instead, we aim to make the monitoring process as straightforward and cost-effective as possible to encourage more people to become aware and take action. Once the EU directive comes into effect in 2027, the market will likely become clearer and more regulated.

Until then, we’re trying to find additional value propositions, such as monitoring bathing water or helping hospitals manage antibiotic use. These applications can provide more immediate benefits and help drive market readiness.

Supertrends: It sounds like there are many current challenges. But let's look a bit further ahead. How do you envision Resistomap in 10 years? What position do you see the company holding in the global health or environmental health landscape?

W.M.: In the long term, we see ourselves contributing to planetary health. Our current focus is on antibiotic resistance and our goal for the next five years is to prevent more potential outbreaks of resistant bacteria. However, in 10 years, we hope to expand our focus to address climate change as well.

Climate change is a growing issue, and our technology is well-suited to measure microbial genes that play important roles in the carbon, nitrogen, and methane cycles. This will help us identify regions that need preservation to manage gas emissions effectively.

Our core technology is rooted in microbiome and microbial ecology, so we aim to contribute to climate change mitigation by understanding how bacteria impact climate-related processes. Our strategy for the next 5-10 years includes expanding our focus to planetary health.

We believe that as global awareness of climate change grows, there will be increased investment in protecting our planet. Our goal is to contribute from a microbiological perspective. While many focus on human health, our approach applies similar principles to environmental health. Just as gut microbiome therapies are used in human health, we aim to apply microbiological insights to planetary health challenges.

Our core technology is quite flexible and can be adapted for various applications. If we choose our targets wisely, we can address different goals effectively.

Supertrends: I really like the idea and mission. Is there anything else you'd like to add before we wrap up?

W.M.: Yes, I’d like to emphasize the importance of global action. Stakeholders in the AMR field need to collaborate closely. Your work in raising awareness through Supertrends is crucial for educating people about both the technology and the problems it addresses.

We want our platform to support global efforts by providing standardized data, regardless of where samples are collected. This allows for meaningful comparisons across different regions and helps us build a comprehensive global map of environmental antibiotic resistance issues.

Our platform is designed to be harmonized and standardized for global use. This way, we can accurately track and compare environmental antibiotic resistance worldwide and promote coordinated global action.

The text is a transcript of an interview conducted on 22 August 2024. The interview was conducted as part of Supertrends' 'Interviews with Experts' series. Please note that the transcript may have been lightly edited for editorial reasons.

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