Tag: Antibiotics

We are hiring a postdoc to work with environmental monitoring of antimicrobial resistance. The project is part of the EMBARK program and will consider different aspects of establishing a baseline for background antibiotic resistance in the environment, standardization of monitoring protocols and development of methods to detect emerging resistance threats. The project will involve work with environmental sampling, DNA extractions, bacterial culturing and generation of large-scale DNA sequence data. In terms of bioinformatic analyses, the project will encompass analysis of next-generation sequence data, genome-resolved metagenomics, short-read assembly and network analysis.

We look for a skilled bioinformatician, preferably with experience of experimental laboratory work. If you feel that you are the right person for this position, you can apply here. More information is also available here. We look forward to your application! The deadline for applications is January 3.

I am very happy to announce today (on the European Antibiotic Awareness Day), that the EMBARK project that I am coordinator for got funded by JPIAMR with almost 1.4 million Euros over three years!

The primary goal of EMBARK is to establish a baseline for how common resistance is in the environment and what resistance types that can be expected where. That background data will then underpin efforts to standardize different methods for resistance surveillance and identify high-priority targets that should be used for efficient monitoring. In addition, EMBARK will develop and evaluate methods to detect new resistance factors and thereby provide an early-warning system for emerging resistance threats.

EMBARK is an international collaboration funded by JPIAMR. The consortium consists of myself, Thomas Berendonk (TU-Dresden, Germany), Luis Pedro Coelho (Fudan University, China), Sofia Forslund (ECRC Max-Delbrück-Centrum für Molekulare Medizin, Germany), Etienne Ruppé (INSERM, France) and Rabaab Zahra (Quaid-i-Azam University, Pakistan).

EMBARK has a website where the protocols and data generated during the project will be released. Follow our progress towards better monitoring of antimicrobial resistance in the environment here and on the EMBARK Twitter account: @EMBARK_JPIAMR!

We are hiring a PhD student to work with effects of antibiotics on microbial communities! The project will use large-scale techniques to investigate how sub-inhibitory concentrations of antibiotics affect microbial communities. Specifically, the project will examine how the ability for bacteria to colonize and invade established microbial communities is impacted by antibiotics. The project will also explore how antibiotics influence the interactions between different species in bacterial communities and if this may change their ability to withstand invasions. The goal is to identify the genes and mechanisms that contribute to change and stability in microbial communities.

A cool thing about this position is that it is fairly adaptable to the eventual candidate, and the project can be somewhat tailored to suit the profile of the PhD student. This means that we’re looking for someone who is either a bioinformatician or an experimentalist (or both). Previous experience with microbial communities is a plus, but not a must.

If you feel that you are the right person for this position, you can apply here. More information is also available here. We look forward to your application! The deadline for applications is December 9.

I have been slow at picking this ball up, but the book chapter that I coauthored with Stefanie Hess is now available online (and has been for almost a month). It is part of the book Antibiotic Drug Resistance, edited by José-Luis Capelo-Martínez and Gilberto Igrejas and was available in print on September 9th.

Our chapter deals with sources of resistant bacteria to the environment, and in particular the roles of sewage, wastewater and agriculture in resistance dissemination. Furthermore, the chapter discusses de novo selection of resistance and defines relevant risk scenarios. Finally, we outline the different management options available and discuss their feasibility.

The chapter boils down to that the available strategies for limiting antibiotic resistance dissemination and selection in the environment are overall quite clear. Larger problems that remain to be solved are how to prioritize between different strategies, which technologies that would provide the largest benefits and to achieve the political willingness to pursue these strategies. We note that several of the most efficient resistance prevention options involve high costs, investments in technology and infrastructure in other countries or proposals that are likely to be rather unpopular with the general public. For example, investing in sewage treatment and water infrastructure in low-income countries would likely be among the most effective means to reduce releases of resistant bacteria into the environment and reduced meat consumption would contribute to lower the use of antibiotics in animal husbandry, but neither is a very popular proposal for tax payers in high-income countries.

I have not yet read the entire book myself, but the table of content shows a very wide-reaching and comprehensive picture of the antibiotic resistance field, with a range of prominent authors. The editors have made a good job collecting this many interesting book chapters in the same volume!

Reference

Bengtsson-Palme J, Heß S: Strategies to reduce or eliminate resistant pathogens in the environment. In: Capelo Martinez JL, Igrejas G (Eds.) Antibiotic Drug Resistance, 637–673. Wiley, NJ, USA (2020). doi: 10.1002/9781119282549.ch24[Link]

This week marked the departure of our summer internship student Alice Zublena, who is now heading back to France to finish her masters program. Alice has been working on establishing effect concentrations for beta-lactam antibiotics for different bacteria, and has generated a very exciting and useful data set for our work in the coming years. I am tremendously happy that I have got to work with Alice this summer and very thankful for having the opportunity to supervise such a talented student. Thanks for your great work this summer Alice and good luck with everything you pursue in the future! 

I celebrate the fourth of July with the coincidental publishing of my most recent paper, in collaboration with the lab of Nikolina Udikovic-Kolic. The study used shotgun metagenomics to investigate the taxonomic structure and resistance gene composition of sludge communities in a treatment plant in Croatia receiving wastewater from production of the macrolide antibiotic azithromycin (1). We compared the levels of antibiotic resistance genes in sludge from this treatment plant and municipal sludge from a sewage treatment plant in Zagreb, and found that the total abundance of resistance genes was three times higher in sludge from the treatment plant receiving wastewater from pharmaceutical production. To our great surprise, this was not true for macrolide resistance genes, however. Instead, those genes had overall slightly lower abundances in the industrial sludge. At the same time, the genes that are associated with mobile genetic elements (such as integrons) had higher abundances in the industrial sludge.

This leads us to think that at high concentrations of antibiotics (such as in the industrial wastewater treatment plant), selection may favor taxonomic shifts towards intrinsically resistant species or strains harboring chromosomal resistance mutations rather than acquisition of mobile resistance genes. Unfortunately, the results regarding resistance mutation – obtained using our recent software tool Mumame (2) – were uninformative due to low number of reads mapping to the resistance regions of the 23S rRNA target gene for azithromycin.

Often, the problem of environmental pollution with pharmaceuticals is perceived as primarily being a concern in countries with poor pollution control, since price pressure has led to outsourcing of global antibiotics production to locations with lax environmental regulation (3). If this was the case, there would be much less incentive for improving legislation regarding emissions from pharmaceutical manufacturing at the EU level, as this would not move the needle in a significant way. However, the results of the paper (and other work by Nikolina’s group (4,5)) underscore the need for regulatory action also within Europe to avoid release of antibiotics into the environment.

References

1. Bengtsson-Palme J, Milakovic M, Švecová H, Ganjto M, Jonsson V, Grabic R, Udiković Kolić N: Pharmaceutical wastewater treatment plant enriches resistance genes and alter the structure of microbial communities. Water Research, accepted manuscript (2019). doi: 10.1016/j.watres.2019.06.073
2. Magesh S, Jonsson V, Bengtsson-Palme J: Quantifying point-mutations in metagenomic data. bioRxiv, 438572 (2018). doi: 10.1101/438572
3. Bengtsson-Palme J, Gunnarsson L, Larsson DGJ: Can branding and price of pharmaceuticals guide informed choices towards improved pollution control during manufacturing? Journal of Cleaner Production, 171, 137–146 (2018). doi: 10.1016/j.jclepro.2017.09.247
4. Bielen A, Šimatović A, Kosić-Vukšić J, Senta I, Ahel M, Babić S, Jurina T, González-Plaza JJ, Milaković M, Udiković-Kolić N: Negative environmental impacts of antibiotic-contaminated effluents from pharmaceutical industries. Water Research, 126, 79–87 (2017). doi: 10.1016/j.watres.2017.09.019
5. González-Plaza JJ, Šimatović A, Milaković M, Bielen A, Wichmann F, Udikovic-Kolic N: Functional repertoire of antibiotic resistance genes in antibiotic manufacturing effluents and receiving freshwater sediments. Frontiers in Microbiology, 8, 2675 (2017). doi: 10.3389/fmicb.2017.02675

I am happy to announce that Cancer- och Allergifonden [the Cancer and Allergy Foundation] have awarded me with the first Lennart Sparell prize. The prize was instated in memory of the foundations founder – Lennart Sparell, who passed away last year – and is awarded to researchers (or other persons) who have thought outside-of-the-box or challenged the current paradigms. A particular emphasis is given to research on environmental pollutants that affect human health through food or environmental exposure.

Naturally, I am honored to be the recipient of this prize. The award was motivated by the research I have done on the role of ecological and evolutionary processes in the external environment in driving antibiotic resistance development, and how that can have consequences for human health. Particularly, I am happy that the research that I, Joakim Larsson, Erik Kristiansson and a few others on the role of environmental processes in the development of antibiotic resistance and the recruitment of novel resistance genes are given attention. This view, which perhaps do not challenge the paradigm but at the very least points to an alternative risk scenario, has often been neglected when environmental antibiotic resistance has been discussed.

The prize will be awarded on a ceremony on June 10 in Stockholm, but I would already now take the opportunity to thank everyone who has been involved in the research being recognized, particularly Joakim Larsson and Erik Kristiansson – this award is to a very very large extent to your merit.

Time flies, and my first 2019 publication (wait what?) is now out! It’s a chapter in the book “Management of Emerging Public Health Issues and Risks: Multidisciplinary Approaches to the Changing Environment” (1), edited by Benoit Roig, Karine Weiss and Véronique Thireau. I have to confess to not having read the other chapters in the book yet, but I think the subject is exciting and hope for a lot of good reading over Christmas here!

My chapter deals with assessment and management of risks associated with antibiotic resistance in the environment (2), and particularly I make an attempt at clarifying the different types of risks and how to deal with them. In short, I partition resistance risks into two categories: dissemination risks and risks for acquisition of new types of resistance (see also 3). While the former category largely encompasses quantifiable risks, the latter is to a large extent impossible (or at least extremely hard) to quantify with current means. This means that we need to be a bit more creative in assessing, prioritizing and managing these risks. Some lessons can be learnt from other fields dealing with very uncertain (and rare) risks, such as asteroid impact assessment, nuclear energy accidents and ecosystem destabilization (4,5). Incorporating elements from such risk management schemes will be necessary to understand and delay emergence of novel resistance in the future.

All these aspects are further discussed in the book chapter (2), which I encourage everyone working with environmental antibiotic resistance risks to read!

References

1. Roig B, Weiss K, Thoreau V (Eds.) Management of Emerging Public Health Issues and Risks: Multidisciplinary Approaches to the Changing Environment. Academic Press/Elsevier, UK (2019). doi: 10.1016/C2016-0-00995-6
2. 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
3. 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
4. WBGU GACOGC: World in Transition: Strategies for Managing Global Environmental Risks. Springer
   Berlin Heidelberg, Berlin, Heidelberg (2000).
5. Government Office for Science: Blackett Review of High Impact Low Probability Events. Department for
   Business, Innovation and Skills, London (2011).

This week, a paper by my former roommate Katariina Pärnänen was published by Nature Communications. In the paper (1), we use shotgun metagenomics to show that infants carry more resistant bacteria in their gut than adults do, irrespective of whether they themselves have been treated with antibiotics or not. We also found that the antibiotic resistance gene and mobile genetic element profiles of infant feces are more similar to those of their own mothers than to those of unrelated mothers. This is suggestive of a pathway of transmission of resistance genes from the mothers, and importantly we find that the mobile genetic elements in breastmilk are shared with those of the infant feces, despite vast differences in their microbiota composition. Finally, we find that termination of breastfeeding and intrapartum antibiotic prophylaxis of mothers are associated with higher abundances of specific ARGs in the infant gut. Our results suggest that infants inherit the legacy of past antibiotic consumption of their mothers via transmission of genes, but that the taxonomic composition of the microbiota still strongly dictates the overall load of resistance genes.

I am not going to dwell in to details of the study here, but I instead encourage you to read the paper (hey, it’s open access!) or the excellent popular summary that Katariina has already written. Finally, I want to emphasize the great work Katariina has put into this (I would know, since I shared room with her) and congratulate her on her own little infant!

Reference

1. Pärnänen K, Karkman A, Hultman J, Lyra C, Bengtsson-Palme J, Larsson DGJ, Rautava S, Isolauri E, Salminen S, Kumar H, Satokari R, Virta M: Maternal gut and breast milk microbiota affect infant gut antibiotic resistome and mobile genetic elements. Nature Communications, 9, 3891 (2018). doi: 10.1038/s41467-018-06393-w [Paper link]

I’m really late at this ball for a number of reasons, but last week Nature published our paper on the structure and function of the global topsoil microbiome (1). This paper has a long story, but in short I got contacted by Mohammad Bahram (the first author) about two years ago about a project using metagenomic sequencing to look at a lot of soil samples for patterns of antibiotic resistance gene abundances and diversity. The project had made the interesting discovery that resistance gene abundances were linked to the ratio of fungi and bacteria (so that more fungi was linked to more resistance genes). During the following year, we together worked on deciphering these discoveries, which are now published in Nature. The paper also deals with the taxonomic patterns linked to geography (1), but as evident from the above, my main contribution here has been on the antibiotic resistance side.

In short, we find that:

• Bacterial diversity is highest in temperate habitats, and lower both closer to the equator and the poles
• For bacteria, the diversity of biological functions follows the same pattern, but for fungi, the functional diversity is higher closer to the poles and the equator
• Higher abundance of fungi is linked to higher abundance and diversity of antibiotic resistance genes. Specifically, this is related to known antibiotic producing fungal lineages, such as Penicillium and Oidiodendron. There also seems to be a link between the Actinobacteria, encompassing the antibiotic-producing bacterial genus of Streptomyces and higher resistance gene diversity.
• Similar relationships between the fungus-like Oomycetes and resistance genes was also found in ocean samples from the Tara Oceans project (2)

The results of this study indicate that both environmental filtering and niche differentiation determine soil microbial composition, and that the role of dispersal limitation is minor at this scale. Soil pH and precipitation seems to be the strongest drivers of community composition. Furthermore, we interpret our data to reveal that inter-kingdom antagonism is important in structuring microbial communities. This speaks against the notion put forward that antibiotic resistance genes might not have a resistance function in natural settings (3). That said, the most likely explanation here is probably a bit of both warfare and repurposing of genes. Soil seems to be the largest untapped source of resistance genes for human pathogens (4), and the finding that natural antagonism may be driving resistance gene diversification and enrichment may be important for future management of environmental antibiotic resistance (5,6).

It was really great to work with Mohammad and his team, and I sure hope that we will collaborate again in the future. The entire paper can be found in the issue of Nature coming out this week, and is already online at Nature’s website.

References

1. Bahram M°, Hildebrand F°, Forslund SK, Anderson JL, Soudzilovskaia NA, Bodegom PM, Bengtsson-Palme J, Anslan S, Coelho LP, Harend H, Huerta-Cepas J, Medema MH, Maltz MR, Mundra S, Olsson PA, Pent M, Põlme S, Sunagawa S, Ryberg M, Tedersoo L, Bork P: Structure and function of the global topsoil microbiome. Nature, 560, 233–237 (2018). doi: 10.1038/s41586-018-0386-6
2. Sunagawa S et al. Structure and function of the global ocean microbiome. Science 348, 6237, 1261359 (2015). doi: 10.1126/science.1261359
3. Aminov RI: The role of antibiotics and antibiotic resistance in nature. Environmental Microbiology, 11, 12, 2970-2988 (2009). doi: 10.1111/j.1462-2920.2009.01972.x
4. 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
5. 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
6. 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).