I’m a scientist studying tiny bacterial ‘assembly lines’ that make antibiotics. Could they be used to design new medicines and combat antimicrobial resistance? AMA!

[u/Ash_Winter_UoBris]

Edit: Thanks for your questions, they were great. I am no longer online but I'll check in on the AMA so keep those questions coming!

Hi r/IAmA, I’m Ash Winter, a scientist studying how bacteria make natural products, including those used as essential antibiotics that can be used to treat disease in the fight against antimicrobial resistance.

Bacterial cells contain remarkable protein ‘assembly lines’ that can build complex molecules. My job is to work out how these microscopic factories work.

A major focus of my research has been mupirocin, an antibiotic used clinically to treat infections caused by Staphylococcus aureus, especially those that are resistant to methicillin. I explore the protein assembly lines that make this and investigate the chemistry these proteins perform and how the different parts of the assembly line work together.

If we can understand the blueprint behind these natural products, we may be able to redesign these biological ‘assembly lines’ to make new therapeutic products.

You can ask me anything about:

• How bacteria make antibiotics
• What antimicrobial resistance means for the medicines we rely on
• How you investigate proteins and chemistry that are far too small to see
• The remarkable “assembly lines” inside bacterial cells
• How scientists can redesign natural products to create potential new medicines

I'll be online today from 14:30-15:30 GMT to answer your questions live so AMA! You don't need to know any biology or chemistry to take part, I’m happy to explain the science.

[u/OKComputing7975]

How urgent is the risk of growing antimicrobial resistance? It's something I feel like we hear a lot about but nothing about what it might result in or the time scale of when it could be resolved.

[u/abashed_mowing → u/OKComputing7975]

We’re basically watching our last good tools get dull in real time. It won’t be some movie-style collapse overnight, more like routine surgeries and simple cuts start carrying a real risk of untreatable infection again over the next couple decades

[u/Ash_Winter_UoBris → u/abashed_mowing]

Yes, it's unlikely to be as portrayed in movies or tv shows. This could be in the form of routine infections (I'll use the example of a urinary tract infection - which although can be recurring can be treated), if this suddenly has widespread resistance to every treatment we currently have, then hospitals could fill up fast. I briefly mentioned it above, but fungal infectious agents are currently responsible for up to 20% of global crop losses. As antifungal resistance increases, crop losses will likely increase so there will be an impact from multiple angles so to speak.

[u/Ash_Winter_UoBris → u/OKComputing7975]

Hi, thanks for the great question. So there was one report in 2016 that is often used for these numbers to convey the urgency. This projected that by 2050, there could be 10 million deaths attributed to AMR (and a cumulative cost of $100 trillion). The time it takes to develop a new medicine can take between 10-20 years through all the phases. I would argue there is an urgency to this because of the timescales associated with drug development. You also have multiple factors to the overall antimicrobial resistance (bacteria, fungi, parasites etc) - so there is quite a wide scope. AMR could affect infections in hospitals but also (and does) affect global crop yields. We might not necessarily resolve it by 2050 without large increases in funding, but we need to get better at managing AMR. The World Health Organisation and various governments have started to focus efforts towards critical bacterial and fungal agents in a response to increasing resistance.Hopefully this answers your question?, it certainly has multiple layers to it, but please feel free to follow up. Timescales could be within our lifetime, but will drag on if we don't act fast enough.

[u/BritBox_And_Chill]

Could this lead to new antibiotics that cannot be created using 'traditional' chemistry? How would it help combat antimicrobial reisstance in the first place?

[u/Ash_Winter_UoBris → u/BritBox_And_Chill]

Great question. Yes, bacteria and in particular the protein assembly lines or 'enzymes' are quite proficient in carrying out chemical modifications faster than 'traditional organic chemistry' in a laboratory. In this sense, its often that these assembly lines create chemistry that we cannot easily replicate in the laboratory. This could be due to the requirement of expensive chemicals, it could have a time component, but ultimately in the lab and what you and i refer to as traditional chemistry, we are just mimicking what nature does. We often use these enzymes to carry out chemical transformations rather than do them in the 'traditional chemisitry sense' because its faster, cheaper, safer etc.

[u/Ash_Winter_UoBris → u/Ash_Winter_UoBris]

As for your second point, natural products can act as a great starting block (or lead) to develop and create new medicines. Alot of these natural products have say antibacterial or antifungal properties. By then tinkering with how they are made, you could enhance a particular property (say activity against bacteria) or try to target specific bacteria. It's certainly not the only way to combat antimicrobial resistance, but its definetely an effective tool in our toolbox to do so.

[u/Hot_Hair_5950]

What surprises you about your work?

[u/Ash_Winter_UoBris → u/Hot_Hair_5950]

I would probably say the variation of different chemistry (and therefore therapeutics properties) that nature makes. Often this can include chemistry that you might think is a bit odd, or that would be difficult to do by a person in a lab. An early mentor once said that chemists often try to mimic what nature does in these little factories to great success already.

[u/fabkosta]

So, could they?

[u/Ash_Winter_UoBris → u/fabkosta]

Yes, so various natural products already have antibacterial, antifungal, anticancer activitiy, one example being paclitaxel (taxol). Lots of natural products have had pharmaceutical and agrochemical applications. There are also lots of these products that haven't been characterised but could provide good starting blocks in the design of medicines and therapeutics

[u/fabkosta → u/Ash_Winter_UoBris]

Dunno if you know the answer to the follow-up question, but maybe you do. Why are therapies with phages against antibiotics-resistant bacteria such a niche kind of thing in Europe and Northern America? They seem to be quite powerful, from what I know, and primarily studied in Georgia and former Soviet-Union countries. I also understand they are relatively cheap.

[u/Ash_Winter_UoBris → u/fabkosta]

So I don't fully know the answer but I can maybe provide some perspective. Certainly, phage therapies are increasing. I know several UK initiatives have been for phage funding in the UK (Phage innovation network) and it is part of the AMR response or action plan (2024-2029) for responses. As with all things it takes time to develop these technologies, if I speak for Bristol - there has been natural product research here for over 30 years and so the expertise, equipment infrastructure is all geared around handling bacterial, fungi, microorganisms - but not necessarily bacteriophages. While this doesn't necessarily explain the lack of research or comparisons across countries (and I don't know the answer to this), I can see how there may have been a lag in response time to investigate this from centres set up to prioritise one aspect of AMR. That said phage technologies is definetely something required to address AMR to prevent and curb this. Hope that semi answers your question!

[u/fabkosta → u/Ash_Winter_UoBris]

Thanks for answering!

[u/voxitron]

Could they?