Category: Thoughts

What is the latent resistome? This is a term we coin in a new paper published yesterday in Microbiome. In the paper, we distinguish between the small number antibiotic resistance genes (ARGs) that are established, well-characterized, and available in existing resistance gene databases (what we refer to as “established ARGs”). These are typically ARGs encountered in clinical pathogens and are often already causing problems in human and animal infections. The remaining latently present ARGs, which we denote “latent ARGs”, are less or not at all studied, and are therefore much harder to detect (1). These latent ARGs are typically unknown and generally overlooked in most studies of resistance. They are also seldom accounted for in risk assessments of antibiotic resistance (2-4). This means that our view of the resistome and its diversity is incomplete, which hampers our ability to assess risk for promotion and spread of yet undiscovered resistance determinants.

In our new study, we try to alleviate this issue by analyzing more than 10,000 metagenomic samples. We show that the latent ARGs are more abundant and diverse than established ARGs in all studied environments, including the human- and animal-associated microbiomes. The total pan-resistomes, i.e., all ARGs present in an environment (including the latent ARGs), are heavily dominated by these latent ARGs. In contrast, the core resistome (the ARGs that are commonly encountered) comprise both latent and established ARGs.

In the study, we identified several latent ARGs that were shared between environments or that are already present in human pathogens. These are often located on mobile genetic elements that can be transferred between bacteria. Finally, we also show that wastewater microbiomes have surprisingly large pan- and core-resistomes, which makes this environment a potent high-risk environment for mobilization and promotion of latent ARGs, which may make it into pathogens in the future.

It is also interesting to note that this new study echoes the results of my own study from 2018, showing that soil and water environments contain a high diversity of latent ARGs (or ARGs not found in pathogens as I put it in the 2018 study), despite being almost devoid of established ARGs (5).

This project has been a collaboration with Erik Kristiansson’s research group, and particularly with Juan Inda-Diáz. It has been great fun to work with them and I hope that we will keep this collaboration going into the future! The study can be read in its entirety here.

References

1. Inda-Díaz JS, Lund D, Parras-Moltó M, Johnning A, Bengtsson-Palme J, Kristiansson E: Latent antibiotic resistance genes are abundant, diverse, and mobile in human, animal, and environmental microbiomes. Microbiome, 11, 44 (2023). doi: 10.1186/s40168-023-01479-0 [Paper link]
2. Martinez JL, Coque TM, Baquero F: What is a resistance gene? Ranking risk in resistomes. Nature Reviews Microbiology 2015, 13:116–123. doi:10.1038/nrmicro3399
3. Bengtsson-Palme J, Larsson DGJ: Antibiotic resistance genes in the environment: prioritizing risks. Nature Reviews Microbiology, 13, 369 (2015). doi: 10.1038/nrmicro3399-c1
4. Bengtsson-Palme J: Assessment and management of risks associated with antibiotic resistance in the environment. In: Roig B, Weiss K, Thoreau V (Eds.) Management of Emerging Public Health Issues and Risks: Multidisciplinary Approaches to the Changing Environment, 243–263. Elsevier, UK (2019). doi: 10.1016/B978-0-12-813290-6.00010-X
5. Bengtsson-Palme J: The diversity of uncharacterized antibiotic resistance genes can be predicted from known gene variants – but not always. Microbiome, 6, 125 (2018). doi: 10.1186/s40168-018-0508-2

I am happy to announce that I am joining the editorial committee of the Swedish Pandemic Preparedness Data Portal (formerly the Swedish COVID-19 portal). I will join five other researchers associated with SciLifeLab and will work together with the portal team to maximise the utility of the Portal for researchers, expand its content beyond SARS-CoV-2, and increase engagement with the research community. My main responsibility areas will be antibiotic resistance and emerging pathogens.

Since 2022 the portal is part of the SciLifeLab Pandemic Laboratory Preparedness (PLP) Program. It is operated by the SciLifeLab Data Centre. Over time, the popularity of the Portal has increased within the research community, the general public, and those involved in healthcare, industry, and policy making. I very much look forward to work with Luisa Hugerth (Uppsala University), Laura Carroll (Umeå University), Benjamin Murrell (Karolinska Institute), Mahmoud Naguib (Uppsala University) and Johan Ankarklev (Stockholm University) on the future of the portal!

UNEP last week published their report on one health responses to antimicrobial resistance (1), which I have taken part in writing (well, I think I ultimately only contributed a few sentences here and there, but apparently that counts to be listed among the report’s contributors). The report, named “Bracing for Superbugs: Strengthening environmental action in the One Health response to antimicrobial resistance” showcases the evidence for that the environment plays a key role in the development, transmission and spread of AMR.

The report tries to unpack the different aspects of environmental AMR, and offers a fairly comprehensive picture of where the science stands on the subject. We also conclude that a systems effort – “One Health” – recognizing that the health of people, animals, plants and the environment are closely connected, is needed to tackle AMR.

This report analyzes the three economic sectors and their value chains that are key drivers of AMR development and spread in the environment: pharmaceuticals and other chemicals, agriculture including the food chain, and healthcare, together with pollutants from poor sanitation, sewage and waste effluent in municipal systems.

I am very happy to have been part of this report writing team and I hope that this will spur future action on AMR from a one-health perspective. You can read the entire report here.

Reference

1. United Nations Environment Programme (2023). Bracing for Superbugs: Strengthening environmental action in the One Health response to antimicrobial resistance. Geneva

Friend, colleague and fellow DDLS Fellow Thomas van Boeckel has just established his research group here in Gothenburg. He is now looking for a new postdoc to identify and extract data to populate resistancebank.org, their database of AMR in animals. Ideally, they are looking for someone with training in microbiology. If you are interested in this position, I encourage you to take a look at this job posting!

I am very happy to share with you that our two doctoral students funded by the Wallenberg DDLS initiative have now started. One of them – Marcus Wenne – is already a well-known figure in the lab, as he has been with us as a master student and then as a bioinformatician for more than a year. The other student – Vi Varga – is a completely new face in the lab and just started yesterday.

Marcus will work in a project on global environmental AMR. He will also continue on his work on large-scale metagenomics to understand community dynamics and antibiotic resistance selection in microbial communities subjected to antibiotics selection. Marcus will work very closely to EMBARK and continue the important work we have done in that project over the next four years.

Vi will study responses of microbial communities to change, with a particular focus on comparative genomics and transcriptional approaches. We will link this to both community stability, pathogenesis and resistance to antibiotics, so this project involves a little bit of everything in terms of the lab’s research interests. Vi’s background is in comparative genomics and pathogenesis, so this seems to be the perfect mix to be able to carry out this project successfully!

Very welcome to the lab Marcus and Vi! We look forward to work with you for the next four years or so!

It’s been a busy couple of days at the DDLS Annual Meeting, so I did not have the time to post about this exciting news yesterday, but it is very exciting nonetheless.

I have been selected by the board of the Royal Swedish Academy of Sciences as the 2022 recipient of the Einhorn SIGHT award. The award recognizes outstanding global health research work by young researchers in the context of low- and middle-income countries, and specifically I have been selected thanks to my “outstanding research and development of tools to limit the global challenge of infectious diseases and antibiotic resistance.”

In a global health context, what is particularly important in the coming years is improved access to clean water and sewage systems. In addition, we also need to develop data-driven systems that can be used to implement easy-to-handle, inexpensive early warning systems and risk models for antibiotic-resistant bacteria, which we hope will be the outcome of the EMBARK program.

Clearly, a large part of this is the result of the work the entire EMBARK team has put together in the past couple of years. Another big part has been the work I have done together with Joakim Larsson in the area of antibiotic resistance in the environment. I am deeply grateful both to Joakim and my EMBARK collaborators for their contributions towards this award. Science is a teamwork, and it is a bit of a pity that we celebrate individuals to the extent we do (even though the recognition of my contribution of course is nice for me personally). Thanks to everyone who have been involved over the years!

There will be an award ceremony at the Royal Academy of Sciences on November 22, as part of a very nice event on Global Health, with the theme ‘Food Safety in conflict’. You can read a short interview I did in relation to the award here.

In other notes, I was also selected as one of Clarivate as one of this year’s Highly Cited Researchers (for the third year in a row!) This is of course also exciting news, although the most important aspect of that is that it shows that the research we do is useful to others!

I will be giving talks on data driven life science – specifically on antibiotic resistance and pathogenicity – on two different events organised within the Data Driven Life Science program (DDLS) in the next month. First up is on the DDLS Annual Conference, coming up already next week (15-16 November). Here, I will give a talk on the evolution of pathogenicity, outlining some of our ongoing work towards finding novel virulence factors. There will also be talk from the other DDLS fellows, as well as Samuli Ripatti and Cecilia Clementi.

On-site registration closes on November 9 so make sure to grab one of the last spots at this exciting event! Register here – online attendance is also possible for those who don’t want to travel to Stockholm.

Then in December, I will be talking at the Data-driven Epidemiology and biology of infections Research Area Symposium in Gothenburg on how to predict the disease threats of the future. This symposium takes place in Gothenburg on December 7 to 8, but again online participation is also possible. Aside from me, Nicholas Croucher will talk about genomic surveillance data and bacterial epidemiology, Bill Hanage will talk about decisions in an imperfect world and Tove Fall will talk about dynamic disease surveillance. There will also be talks about the new DDLS fellows in epidemiology and infection biology, which is what I am perhaps most excited about: Thomas van Boeckel, Luisa Hugerth and Laura Carroll! It seems like registration has not yet opened for this event, but keep monitoring this site.

I look forward to see you at these events!

I became quite happy this morning while scanning though the new Chalmers recruitments for new assistant professors in the Area of Advance calls this year (unfortunately this news item went out only on the intranet for some reason, but I will recap with names for easy googling).

Out of 15 recruitments, 10 are women – that’s almost 70%, which must be regarded very positive in terms of gender balance at a university with a male-dominated faculty. Of the five men, only two seem to be of European background, with the other three being non-white from different cultural spheres. In the end, only two out of fifteen (<15%) are the “traditional” Swedish university type (white men) who dominate the Chalmers faculty today.

Well done with the recruitments, especially if these are also the best persons for the positions (which I assume they are given how hard these positions are to get!) Also, good luck to the new PIs, I have already spoken to two of them who will land at the same department as I am in, and I can’t wait to start working with these brilliant minds!

Here’s the complete list of recruitments:

• Mathilde Luneau, Area of Advance Energy – Department of Chemistry and Chemical Engineering
• Alexander Giovannitti, Area of Advance Material – Department of Chemistry and Chemical Engineering
• Varun Chaudhary, Production Area of Advance – Department of Industrial and Materials Science
• Maud Lanau, Sustainable Cities – Department of Architecture and Civil Engineering
• Margaret Holme, Basic science – Department of Biology and Biological Engineering
• Annikka Polster, Health Engineering Area of Advance – Department of Biology and Biological Engineering
• Eszter Lakatos, Health Engineering Area of Advance – Department of Mathematical Sciences
• Elena Pagnin, Information and Communication Technology Area of Advance – Department of Computer Science and Engineering
• Ilaria Torre, Technology in Society – Department of Computer and science engineering
• Kun Gao, Transport Area of Advance – Department of Architecture and Civil Engineering
• Angela Grommet, Excellence Initiative Nano – Department of Chemistry and Chemical Engineering
• Georgia Panopoulou, Basic Science – Department of Space, Earth and Environment
• Hans Chen, Basic Science – Department of Space, Earth and Environment
• Saara Matala, Technology in Society – Department of Technology Management and Economics
• Nils Johan Engelsen, Excellence Initiative Nano – Department of Microtechnology and Nanoscience

Last week, we published a paper which has been cooking for a long time. It is the result of years of hard work from particularly the first author – Tove Wikström – but also Sanna who did the bulk of the bioinformatic analysis with some help from me (well, I mostly contributed as a sounding board for ideas, but hopefully that was useful). The paper describes the gene expression of both the human host and the microbial community in the vagina during pregnancy and how the expressed genes (and the composition of bacteria) are linked to early births (1) and was published in Clinical and Translational Medicine.

We found 17 human genes potentially influencing preterm births. Most prominently the kallikrein genes (KLK2 and KLK3) and four different forms of of metallothioneins (MT1s) were higher in the preterm group than among fullterm women. These genes may be involved in inflammatory pathways associated with preterm birth.

We also found 11 bacterial species associated with preterm birth, but most of them had low occurrence and abundance. In contrary to some earlier studies, we saw no differences in bacterial diversity or richness between women who delivered preterm and women who delivered at term. Nor did Lactobacillus crispatus – often proposed to be protective against preterm birth (2,3) – seem to be a protective factor against preterm birth. However, most other studies have used DNA-based approaches to determine the bacterial community composition, while we used a metatranscriptomic approach looking at only expressed genes. In this context it is interesting that other metatranscriptomic results (4) agree with ours in that it was mainly microbes of low occurrence that differed between the preterm and term group.

Overall, the lack of clear differences in the transcriptionally active vaginal microbiome between women with term and preterm pregnancies, suggests that the metatranscriptome has a limited ability to serve as a diagnostic tool for identification of those at high risk for preterm delivery.

Great job Tove and the rest of the team! It was a pleasure working with all of you! The entire paper can be read here.

References

1. Wikström T, Abrahamsson S, Bengtsson-Palme J, Ek CJ, Kuusela P, Rekabdar E, Lindgren P, Wennerholm UB, Jacobsson B, Valentin L, Hagberg H: Microbial and human transcriptome in vaginal fluid at midgestation: association with spontaneous preterm delivery. Clinical and Translational Medicine, 12, 9, e1023 (2022). doi: 10.1002/ctm2.1023 [Paper link]
2. Kindinger LM, Bennett PR, Lee YS, et al.: The interaction between vaginal microbiota, cervical length, and vaginal progesterone treatment for preterm birth risk. Microbiome, 5, 1, 1-14 (2017).
3. Tabatabaei N, Eren AM, Barreiro LB, et al.: Vaginal microbiome in early pregnancy and subsequent risk of spontaneous preterm birth: a case-control study. BJOG, 126, 3, 349-358 (2019).
4. Fettweis JM, Serrano MG, Brooks JP, et al.: The vaginal microbiome and preterm birth. Nature Medicine, 25, 6, 1012-1021 (2019).

Together with 1943 other Swedish scientists, I co-signed an opinion article in the Swedish newspaper Aftonbladet with the translated title “Enough, politicians – take climate change seriously“. In short, we argue that the facts have been on the table of many years, but little action has been undertaken. Compare the action taken against covid-19 to the dull inaction taken to address the climate crisis, and you may see where the frustration comes from. Action is still possible, but not if we refuse to acknowledge climate change as a problem. The piece ends with (my translation):

The situation is dire – the emissions continue to rise when they would need to be dramatically reduced. We now plead with all politicians in Sweden: put the climate crisis on the top of the agenda! Use the available scientific expertise; start by enacting the recommendations you have already got from the Climate council.

Treat the climate crisis as the acute and life changing crisis it is, and show political leadership!

The opinion piece can be read here (in Swedish)