Tag: EMBARK

Together with Anna Székely, I have been working on the organization of a DDLS Symposium on Data-Driven Environmental Monitoring of Infectious Diseases on October 7 – 8, in Uppsala.

The symposium will focus on promoting and enhancing data-driven environmental assessment for infectious diseases (including antibiotic-resistant bacteria) across various settings using diverse approaches. We now invite submission of abstracts for short talks.

Deadline for abstract submission: 18 September 
Deadline to register to attend: 25 September –> REGISTER HERE! <– This includes abstract submission.

Link to more information and the PROGRAM

I hope to see all of you working with AMR in the environment in Uppsala in October!

This paper came out just about the same time as the PhD position with Erik Kristiansson where I will be co-supervisor was announced, and I did not want to steal that thunder with another news item, but it is now time to highlight the fantastic work of Víctor Hugo Jarquín-Díaz on antibiotic resistance genes in the gut microbiomes of mice across a gradient of pure and hybrid genotypes in the European house mouse hybrid zone. This came out in mid-April in ISME Communications and presents the interesting hypothesis that hybridisation not only shapes bacterial communities, but also antibiotic resistance gene occurrences (1).

This study is based on 16S rRNA amplicon sequencing of gut bacteria in natural populations of house mice. From this we have predicted the antibiotic resistance gene composition in the microbiomes, and found a significant increase in the predicted antibiotic resistance gene richness in hybrid mice. In other words, more and different antibiotic resistance genes were found in the hybrid mice than in the non-hybridised individuals. We believe that this could be due to a disruption of the microbiome composition in hybrid mice. The aberrant microbiomes in hybrids represent less complex communities, potentially promoting selection for resistance.

It deserves to be mentioned that this is more of a pilot study, which we hope to follow up with a more proper study targeting the resistance genes in the mice microbiomes. That said, our work suggests that host genetic variation impacts the gut microbiome and antibiotic resistance gene, at least in mice. This raises further questions on how the mammalian host genetics impact antibiotic resistance carriage in bacteria via microbiome dynamics or interaction with the environment.

I am very happy to have been part of this EMBARK collaboration with the Sofia Forslund-Startceva and Emanuel Heitlinger labs! And I am especially thankful to Víctor who pulled off this very thought-inducing study!

Reference

1. Jarquín-Díaz VH, Ferreira SCM, Balard A, Ďureje Ľ, Macholán M, Piálek J, Bengtsson-Palme J, Kramer-Schadt S, Forslund-Startceva SK, Heitlinger E: Aberrant microbiomes are associated with increased antibiotic resistance gene load in hybrid mice. ISME Communications, ycae053 (2024). doi: 10.1093/ismeco/ycae053 [Paper link]

I just want to point potential doctoral students’ attention to this fantastic opportunity to work with my EMBARK colleague Luis Pedro Coelho as he sets up his new lab in Brisbane in Australia at the relatively new Centre for Microbiome Research. Luis is looking for two PhD students, one who will focus on identifying and characterising the small proteins of the global microbiome and one more related to developing novel bioinformatic methods for studying microbial communities.

I can highly recommend this opportunity given that you are willing to move to Australia, as Luis is one of the most brilliant scientists I have worked with, is incredibly easy-going and fosters a lab culture I strong support. More information and application here.

On the 5th and 6th of October this year, I will be taking part in a relatively small, but very interesting conference on veterinary and environmental AMR, held in Amsterdam. The theme of the event will be “Optimal practices to protect human health care from antimicrobial resistance selected in the veterinary domain”.

The aim of the conference is to discuss innovative additional measures to prevent development of resistance in animals. In addition, the participants will explore possibilities to prevent transfer to human health care after selection has taken place. The conference program will consist of both lectures and break-out sessions and is intended for researchers as well as for policy makers involved in the battle against antimicrobial resistance. The results of the break-out sessions are to be published in an open access journal, and I will be charing one of these break-out sessions. Please see the conference web site for the entire program: https://www.nvwa.nl/amrconference

There is an upper cap of 120 participants for the event, so if you’re interested make sure to register soon! The conference will be held on October 5 and 6 2023 in the Park Inn by Radisson in Amsterdam, The Netherlands. The hotel is easy to reach by a 12 minutes train ride from Schiphol airport and a 5 minutes train ride from the city center. 

I look forward to seeing you in Amsterdam!

In just a few days, Environment International has published two papers coming out from the EMBARK consortium which are somewhat connected to each other.

The first (or technically the second, but the other order makes more sense when explaining this…) is the first paper involving most of the people who have been working in the EMBARK consortium for an extended period of time. It’s an overview paper titled “Towards monitoring of antimicrobial resistance in the environment: For what reasons, how to implement Itit, and what are the data needs?” (1) and I think the title describes the topic pretty well. Basically, we go through why it would be interesting to monitor for antibiotic resistance in the environments, how that could be implemented and what we would need to know to get there.

The very condensed story is that if one is considering implementing monitoring for environmental resistance, these are a few things that should be considered:

• The purpose of monitoring: What is the motivation? What should be achieved? What type of risk should be assessed? What type of action would monitoring enable?
• Choice of methods: Which methods are economically feasible? Which methods would deliver results within a useful timeframe for taking appropriate actions?
• Targeted environments: In what type of environment would monitoring for a given purpose be worthwhile?
• Intended users: Who would be able to use, implement and act upon this strategy?
• Integration potential: How does this monitoring integrate with other monitoring efforts? How can the resulting data be communicated?

We then dive into the knowledge gaps we are currently facing, and particularly highlight the following areas:

• Establish how different existing methods for monitoring resistance compare to each other
• Extend pathogen-centric databases for resistance genes with latent resistance genes (2)
• Determine the locations and type of environments relevant for resistance monitoring
  To reduce costs, utilizing already existing environmental monitoring should be prioritized, as should locations integrated into operating or planned surveillance programs. More efforts should also be made to identify additional pathways for resistance transmission through the environment.
• Study the environment as a source and transmission route for antibiotic resistance
  Stratify risks associated with resistance genes found in the environment. Define typical levels of antibiotic resistance in different environments (3), and define how these levels change over time.
• Identify settings where the relationship between fecal bacteria and antibiotic resistance is absent
  Usually, these levels follow each other, but the environments where they don’t are important as they deviate from the expected baseline of resistance. This knowledge can aid in identifying situations in which it would be helpful to investigate a microbial community for resistance to specific antibiotics.
• Identify the origins for more antibiotic resistance genes (4)
  This knowledge will be instrumental in preventing the emergence of new forms of resistance in pathogens in the future.

An important outcome of this paper is that we realise that we are still not at a level of understanding where routine monitoring for resistance in the environment can be easily justified or implemented. Still, there is a need for monitoring data in natural environments to even get started, and therefore we support the implementation of national, regional and global of initiatives without having all the scientific answers. The lack of comprehensive understanding should not be an obstacle to starting environmental monitoring for AMR, nor for action against environmental development and spread of AMR.

The second paper is very much related to the first, in that it actually tries to address one of these knowledge gaps: the need for normal background levels of antibiotic resistance in different environments. In this paper, Anna Abramova did an herculean effort collecting (we hope) all qPCR data on antibiotic resistance gene abundances in the environment for the past two decades. All in all, she collected data for more than 1500 samples across 150 studies and integrated these into an analys of what we could consider normal levels of resistance in different environments.

For an ‘average’ resistance gene, we found that the normal relative abundance range was form 10^-5 to 10^-3 copies per bacterial 16S rRNA, or that around one in 1,000 bacteria would carry a given resistance gene. This level varied quite a bit between different resistance genes, however, but not so much between environmental types (except for in human and animal feces, where some resistance genes were clearly more abundant, most prominently tetracycline resistance genes). What was more striking was that there was a clear difference between environments impacted or likely impacted by human activities, as opposed to more pristine environments with little to none human impact. Some resistance genes, such as tetA, tetG, blaTEM and blaCTX-M, showed very marked differences between these impacted and non-impacted environments, making them great markers of human-activity-associated resistance.

Our final recommendations with regards to monitoring include:

• Include the intI1, sul1, blaTEM, blaCTX-M and qnrS genes in environmental monitoring, along with a selection of tetracycline resistance genes, including either tetA or tetG.
• Other potential target genes could be sul3, vanA, tetH, aadA2, floR, ereA and mexF, which are abundant in some environments, but are not often included in qPCR studies of environmental AMR
• If a gene deviates from the expected 10^-5 to 10^-3 interval, this warrants further investigation of the causes.
• Maximum acceptable levels need to be determined not only taking relative abundances of genes into account, but also risks to human health as well as the numbers of bacteria in a given volume of sample into account (5,6) and transmission routes to humans (7)
• The different standards of reporting DNA abundances constituted a complicating factor for this study. Both abundances of resistance genes relative to the 16S rRNA gene and to the sample volume or weight should be reported.
• The absence of clear trends of increases or decreases in resistance gene abundances over time indicates a need for more systematic time series data in a variety of environments.

Our results also highlighted the scarcity of resistance gene data from parts of the world, particularly from Africa and South America, and underscores the need for a concerted effort to quantify typical background levels of resistance in the environment more broadly to enable efficient environmental surveillance schemes akin to those that exist in clinical and veterinary settings.

I encourage anyone with an interesting these topics to at least skim the full papers [Monitoring overview paper here, Normal qPCR resistance abundances here]. These will be great resources and I am very proud of them both. I would really like to thank the entire EMBARK team and our collaborators in CORNELIA, WastPAN and in other organisations. I would also like to thank Anna for her hard work on collecting and analysing the qPCR data for around two years. It has been a long ride, and I think we are both happy, proud and a bit relieved to finally see this paper published!

References

1. Bengtsson-Palme J, Abramova A, Berendonk TU, Coelho LP, Forslund SK, Gschwind R, Heikinheimo A, Jarquin-Diaz VH, Khan AA, Klümper U, Löber U, Nekoro M, Osińska AD, Ugarcina Perovic S, Pitkänen T, Rødland EK, Ruppé E, Wasteson Y, Wester AL, Zahra R: Towards monitoring of antimicrobial resistance in the environment: For what reasons, how to implement it, and what are the data needs? Environment International, 108089 (2023). doi: 10.1016/j.envint.2023.108089
2. 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
3. Abramova A, Berendonk TU, Bengtsson-Palme J: A global baseline for qPCR-determined antimicrobial resistance gene prevalence across environments. Environment International, 178, 108084 (2023). doi: 10.1016/j.envint.2023.108084
4. Ebmeyer S, Kristiansson E, Larsson DGJ: A framework for identifying the recent origins of mobile antibiotic resistance genes. Communications Biology, 4 (2021). doi:10.1038/s42003-020-01545-5
5. Larsson DGJ, Andremont A, Bengtsson-Palme J, Brandt KK, de Roda Husman AM, Fagerstedt P, Fick J, Flach C-F, Gaze WH, Kuroda M, Kvint K, Laxminarayan R, Manaia CM, Nielsen KM, Ploy M-C, Segovia C, Simonet P, Smalla K, Snape J, Topp E, van Hengel A, Verner-Jeffreys DW, Virta MPJ, Wellington EM, Wernersson A-S: Critical knowledge gaps and research needs related to the environmental dimensions of antibiotic resistance. Environment International, 117, 132–138 (2018). doi: 10.1016/j.envint.2018.04.041
6. Pruden A, Larsson DGJ, Amézquita A, Collignon P, Brandt KK, Graham DW, et al. Management options for reducing the release of antibiotics and antibiotic resistance genes to the environment. Environmental Health Perspectives, 121, 878–885 (2013). doi:10.1289/ehp.1206446
7. Bengtsson-Palme J, Kristiansson E, Larsson DGJ: Environmental factors influencing the development and spread of antibiotic resistance. FEMS Microbiology Reviews, 42, 1, 68–80 (2018). doi: 10.1093/femsre/fux053

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!

In this episode Microbiology Lab Pod, the team (Johan Bengtsson-Palme, Emil Burman, Anna Abramova, Marcus Wenne, Sebastian Wettersten and Mahbuba Lubna Akter, Shumaila Malik, Emilio Rudbeck and Camille Wuyts) discusses the evolution of antibiotic resistance from different perspectives. We also interview Rémi Gschwind about his work on novel antibiotic resistance genes in the EMBARK program.

The specific papers discussed in the pod (with approximate timings) are as follows:

• 7:45 – EMBARK website: http://antimicrobialresistance.eu
• 26:15 – Seemann, T., 2014. Prokka: rapid prokaryotic genome annotation. Bioinformatics 30, 2068–2069. https://doi.org/10.1093/bioinformatics/btu153
• 29:00 – Bengtsson-Palme, J., Larsson, D.G.J., 2015. Antibiotic resistance genes in the environment: prioritizing risks. Nature reviews Microbiology 13, 396. https://doi.org/10.1038/nrmicro3399-c1
• 29:30 – Ebmeyer, S., Kristiansson, E., Larsson, D.G.J., 2021. A framework for identifying the recent origins of mobile antibiotic resistance genes. Communications Biology 4. https://doi.org/10.1038/s42003-020-01545-5
• 54:15 – Gillings, M.R., Stokes, H.W., 2012. Are humans increasing bacterial evolvability? Trends in Ecology & Evolution 27, 346–352. https://doi.org/10.1016/j.tree.2012.02.006
• 55:15 – Woods, L.C., et al., 2020. Horizontal gene transfer potentiates adaptation by reducing selective constraints on the spread of genetic variation. Proc Natl Acad Sci USA 117, 26868–26875. https://doi.org/10.1073/pnas.2005331117
• 76:15 – Card, K.J., Thomas, M.D., Graves, J.L., Barrick, J.E., Lenski, R.E., 2021. Genomic evolution of antibiotic resistance is contingent on genetic background following a long-term experiment with Escherichia coli. Proc Natl Acad Sci USA 118, e2016886118. https://doi.org/10.1073/pnas.2016886118

The podcast was recorded on March 18, 2021. If you want to reach out to us with comments, suggestions, or other feedback, please send an e-mail to podcast at microbiology dot se or contact @bengtssonpalme via Twitter. The music that can be heard on the pod is composed by Johan Bengtsson-Palme and is taken from the album Cafe Phonocratique.

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Not only did we release the most recent episode of the lab’s podcast this weekend. Today, the episode of The AMR Studio where I’m interviewed by Eva Garmendia of the Uppsala Antibiotic Center was put online. We talk mostly about antibiotic resistance in the environment and the role that the EMBARK program can play in mitigating environmental resistance. I think it’s a nice listen (recorded in the beautiful world pre-covid-19). Find it where you find podcasts (e.g. Apple or Spotify).

Here’s some updates on my Spring schedule.

On March 19, I will be presenting the EMBARK program and what we aim to achieve at a conference organised by the Swedish Medical Products Agency called NordicMappingAMR. The event will feature an overview of existing monitoring of antibiotics and antibiotic resistant bacteria in the environment. The conference aims to present the results from this survey, to listen to experts in the field and to discuss possible progress. It takes place in Uppsala. For any further questions, contact Kia Salin at NordicMappingAMR@lakemedelsverket.se

Then on May 18 to 20 I will participate in the 7th Microbiome & Probiotics R&D and Business Collaboration Forum in Rotterdam. This industry/academia cross-over event focuses on cutting-edge microbiome and probiotics research, and challenges and opportunities in moving research towards commercialisation. I will talk on the work we do on deciphering genetic mechanisms behind microbial interactions in microbiomes on May 20.

And finally, I also want to bring the attention to that my collaborator Erik Kristiansson has an open PhD position in his lab. The position is funded by the Environmental Dimensions of Antibiotic Resistance (EDAR) research project, aiming to describe the environmental role in the development and promotion of antibiotic resistance. The focus of the PhD position will be on analysis of large-scale data, with special emphasis on the identification of new forms of resistance genes. The project also includes phylogenetic analysis and development of methods for assessment of gene evolution. More info can be found here.