Anti-infective natural substances


The department "Anti-infectives from Microbiota" of Prof Christine Beemelmanns focuses on the identification and functional analysis of novel anti-infective natural products from microbial communities. Co-cultivation studies and cell-based assays in combination with chemical-analytical and molecular biological methods are used to evaluate new microbial natural product producers. The group uses established and innovative metabolomic, activity- and genome-guided methods to elucidate the structure of the secreted natural products. Based on the isolated natural products, the functional analysis and evaluation of their spectrum of activity is carried out. The department is based at the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) in Saarbrücken, a site of the HZI in co-operation with Saarland University.

The spread of antibiotic-resistant human pathogenic bacteria is an increasing threat to human health. The development of new anti-infectives and a better understanding of their function and mode of action are therefore urgently needed. Microorganisms are a promising source of new active substances. Microbial communities (microbiota / microbiome) are made up of a large number of different bacteria, fungi and representatives of unicellular and few-celled eukaryotes as well as viruses. These communities are found on human, animal and plant tissue surfaces, among others, where they can fulfil essential functions for the host. In many cases, the composition of the microbiota correlates with its localisation and thus its function. Microorganisms regulate and manipulate their coexistence by emitting bioactive natural substances. Microbial natural products can have an antibiotic effect to protect the producers, but can also act as a cellular signal, as a morphogen for the host organism or be metabolised as a nutrient. However, the chemical structures of many of these natural substances are unknown, which means that their natural function, their influence on the microbiota and their potential applications are still poorly understood.

As natural products play important roles in microbial interactions, their production is closely linked to the composition of the microbiota. The Beemelmanns group analyses representative microbial communities to explore this chemical space.

Find out about our scientific work at Helmholtz Centre for Infection Research.

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00:00:00: Imagine being in the forest on a beautiful day and taking a deep breath.

00:00:07: Can you smell that scent?

00:00:12: It also comes from the microorganisms in the forest floor,

00:00:18: but these microorganisms don't just make the forest scent.

00:00:22: With the natural substances they produce,

00:00:24: they also provide us with the basis for medicinal substances, for new medicines,

00:00:30: because we need them against new pathogens and pathogens that have developed resistance to old drugs,

00:00:37: and also against diseases that we are not able to cure.

00:00:42: Yet, Professor Christine Beemelmans knows the potential of these bio-coenoses that we find in the soil,

00:00:49: or even in water. She heads the Department of Anti-Infectives from Microbiota

00:00:55: at the Helmholtz Institute for Pharmaceutical Research, Saarland, HIPPS, for short.

00:01:00: Today, we are talking about these huge, diverse communities made up of all kinds of tiny organisms,

00:01:07: about the substances they produce and why they are so interesting for drug research.

00:01:15: How do bacteria and viruses trigger diseases?

00:01:19: How does our immune system defend itself against them,

00:01:22: and what must active substances be able to do to fight dangerous infections?

00:01:29: The Helmholtz Center for Infection Research is looking for answers to these questions.

00:01:34: How this research works, how the results are used in medicine,

00:01:38: and who the people are that do the work.

00:01:41: This you can listen to here at InFact, the podcast of the Helmholtz Center for Infection Research.

00:01:53: I'm here in the Helmholtz Institute for Pharmaceutical Research, Saarland, HIPPS,

00:01:59: with the Natural Products Researcher, Professor Christine Beemelmans. Hi.

00:02:04: Hello.

00:02:06: What are your actually researching here?

00:02:09: My group's research is focused on the microbes, meaning bacteria and fungi,

00:02:14: and we want to find out how these organisms live together,

00:02:19: and especially how they communicate with each other,

00:02:22: and that's what they are normally doing by natural products.

00:02:26: Natural products sometimes sounds a bit like "mangiival" or like "alternative medicine",

00:02:34: but why is it really a highly topical and highly scientific research field?

00:02:40: Natural product research has always been very important, also in the medieval ages,

00:02:46: because that's how they treated patients also at that time.

00:02:50: And you also have to consider natural products are very old.

00:02:53: Bacteria and fungi are very old, and they have producing them ever since,

00:02:58: since they basically developed the capabilities to do so,

00:03:02: and that's dating millions of years back, so they have been always around us.

00:03:07: And I think that's why microorganisms are such good sources of active products

00:03:15: that can be developed into new drugs.

00:03:18: Correct. So they have the genetic capabilities to basically produce these compounds,

00:03:23: and we are taking use of that.

00:03:25: First of all, we want to understand how these microbes interact,

00:03:28: to also understand how beneficial good microbes can actually live in us or in other organisms,

00:03:34: and also how we can use their natural product repertoire to fend off diseases

00:03:39: which are often caused by actually pathogenic, fungi or pathogenic bacteria.

00:03:45: You have already researched natural products in various biosynosis,

00:03:51: for example at the Leibniz Institute for Natural Product Research in Jena,

00:03:56: on termites and hydructenia, aquatic animals that form colonies.

00:04:04: What else can you, where else can you find natural products?

00:04:09: You can basically find them everywhere.

00:04:11: So we chose these two symbiotic systems because they are very old,

00:04:16: so the termite system dates back 40 million years.

00:04:19: So that means the organisms have interacted since then with each other,

00:04:24: meaning the insects together with the bacteria and fungi.

00:04:27: So they have co-evolved and the natural products in the system were anticipated to play a role in the system for a long time.

00:04:34: So we wanted to understand this very, very old system.

00:04:38: The same for the marine system.

00:04:40: Many marine organisms actually developed 100 of million years ago

00:04:44: and have been interacting with bacteria ever since.

00:04:47: So that means natural products in the system probably also very old and have certain functions.

00:04:53: And that was our intrinsic interest in that.

00:04:55: So now looking around us, of course, all our organisms, like us humans,

00:04:59: they have a bacteria which have been there for a long time already.

00:05:03: So meaning they have certain functions and also produce certain natural products which we don't know yet of.

00:05:08: So in the structures we don't know yet.

00:05:10: So now we talked a lot about microorganisms, where you can find them and which products they produce.

00:05:19: But how do you get these products?

00:05:22: Yeah, for that you need actually interdisciplinary team because you need microbiologists

00:05:28: who are capable of cultivating these organisms.

00:05:31: And at the same time you also need analytical chemists,

00:05:34: meaning people who are trained to analyze substances, to characterize them

00:05:39: and also to produce them in such a quality that you can actually do bioassays.

00:05:45: So for that you need people or scientists from various different fields.

00:05:50: But even if I'm not a scientist, I can help find natural products.

00:05:56: How can I do that?

00:05:56: Yeah, we have actually a citizen science project, which was initiated here in this institute.

00:06:02: And you can basically request online a box which contains a sample kit.

00:06:09: We have basically a box for collection.

00:06:11: And then you can just send in these samples and you can collect them everywhere in your

00:06:15: garden, in your backyard, in front of your door, wherever you want.

00:06:19: And then just send basically with the box also the information where you got the sample.

00:06:25: And we will process them here.

00:06:28: Cool.

00:06:29: So I can take a kit with me and send some samples from Cologne.

00:06:35: Yeah, sure.

00:06:36: You can also take several kits.

00:06:37: So how much you like.

00:06:40: And if you're not here, you can request them online and they are being shipped to you.

00:06:44: And then it's also free shipping back to the institute.

00:06:47: This is a good service.

00:06:50: But the incredible number of different species and therefore substances or products that

00:06:55: you can find, how many products are actually researched further and how many of them end

00:07:02: up becoming drugs?

00:07:03: Yeah, that's a good and critical question.

00:07:08: Of course, first of all, when we identify natural products in the settings of our systems

00:07:14: or also within other groups, they can have different functions than natural products

00:07:19: because they were not made by the organisms for our purposes.

00:07:22: But we want to modulate them so that we can use them further.

00:07:27: So there's very difficult to say a number to it.

00:07:30: But at the end, if we have, if we fill the pipeline with enough compounds, the probability

00:07:35: to actually get drug leads or compounds for a certain aim, it's increasing.

00:07:40: If you don't fill the pipeline, we will not get any candidates.

00:07:44: So at the end, if you have, for example, 1000 compounds and you end up with two, three very

00:07:49: promising drug leads, that's already something.

00:07:53: So it's basically like a reverse pyramid.

00:07:56: So if you fill in a lot of compounds, you will at the end also end up with a couple of

00:08:00: compounds which can then go into preclinics or even further.

00:08:04: But I think it's a huge database.

00:08:08: How is that managed?

00:08:09: Yeah.

00:08:10: We, of course, every group has its own data management, but we also have basically a collection

00:08:15: of strains where all of the HZI, all of the people who are belonging to the center can

00:08:22: retrieve from.

00:08:24: Also the data related to the natural products itself can be basically retrieved by the groups

00:08:29: or requested.

00:08:30: So if compounds are, for example, showing promising activity in one direction, they can also be

00:08:36: explored into other directions.

00:08:38: So data management is always a very important aspect so that not something lands in a rubbish

00:08:44: bin just because nobody knows about it.

00:08:49: You mentioned the HZI.

00:08:51: How does your work here at the HIPPS relate to the work of your colleagues at the HZI?

00:08:59: It relates very much because we are also researching on common topics.

00:09:03: So for example, in the group of Mark Stadler, they are very interested in fungal natural

00:09:07: products and their bio activities.

00:09:10: So that relates very much to exploring also different sources, also taxonomically unique

00:09:15: sources.

00:09:16: And these natural products are also important for screening here.

00:09:20: Or we are also working on certain fungal taxa, which are of importance for them.

00:09:24: So that's very mutual interests.

00:09:27: And for example, in the topic of chemical biology, once we have natural products of

00:09:31: importance with important scaffolds, they can be processed further synthetically, semi-synthetically

00:09:37: in the group of, for example, Mark Brunstrup, or further develop for the mode of action

00:09:41: studies.

00:09:42: Wow.

00:09:43: But you did not only research here in Germany, but also in Japan and in the US.

00:09:52: What could we learn from them and what could they learn from us?

00:09:56: Yeah, so being in different countries, of course, is an experience everybody should

00:10:02: have or it's a research environment is quite different in other countries.

00:10:07: At the end, of course, we have the Germans saying that everybody cooks with water.

00:10:10: So at the end, the research is done in similar ways.

00:10:13: But the way how we approach this approach to research are different sometimes.

00:10:18: So especially the enthusiasm, the positive approaches to explore new avenues.

00:10:25: That's something, a feature which I find in the US very interesting and also important,

00:10:31: something that I learned there to really go with a very positive attitude towards it

00:10:36: and that we can really make it.

00:10:38: And from Japan, I basically also learned that you really have to be like insisting on problems,

00:10:44: even if you have a little bit to work harder than usual.

00:10:48: But you have to find the balance between both.

00:10:50: So one last question.

00:10:52: In your free time, do you always have a sample tube with you?

00:10:56: Yeah, normally, yes.

00:10:59: So in my free time, I work a lot in the garden or doing sports.

00:11:03: But normally if you go outside, you always have sample tubes with us.

00:11:09: Thank you for the fascinating talk about microorganisms and the natural products they produce.

00:11:14: Thank you.

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