Tag: Antibiotics

My PhD supervisor Joakim Larsson has an opening for a PhD student at University of Gothenburg. The project is on the role of different wastewaters in the evolution of antibiotic resistance, and will be centered on bioinformatic analyses of large-scale data. The project will encompass analysis of bacterial growth curve data through machine learning to antibiotics with selective effects in different wastewaters. Comparative genomics and different AI-based approaches will be applied to large-scale public genome and metagenome data to better understand how resistance genes are mobilized and transferred to pathogens.

Joakim is a great scientist with a vibrant group, so if your interests is in line with the position, I strongly suggest you take a look at it! Deadline is October 30! Application link here: https://web103.reachmee.com/ext/I005/1035/job?site=7&lang=UK&validator=9b89bead79bb7258ad55c8d75228e5b7&job_id=30401

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!

Together with our collaborators in Tromsø in Norway, we published a paper over the weekend in eBioMedicine describing the early colonization patterns of preterm infants, both in terms of the microbes that arrive early to the infants, but also in terms of the antibiotic resistance genes they carry.

In the paper (1), which is a continuation of an earlier study by part of the team (2), we analysed metagenomic data from six Norwegian neonatal intensive care units to better understand the bacterial microbiota of infants born preterm or on term and receiving different treatments. These groups included probiotic-supplemented and antibiotic-exposed extremely preterm infants (n = 29), antibiotic-exposed very preterm infants (n = 25), antibiotic-unexposed very preterm infants (n = 8), and antibiotic-unexposed full-term infants (n = 10). Stool samples were collected from the infants after 7, 28, 120, and 365 days of life and were analysed using shotgun metagenomics. We were particularly interested in the maturation of the preterm infant microbiome into a ‘normal’ healthy gut microbiome, and the colonization with bacteria carrying antibiotic resistance genes.

We found that microbiota maturation was largely determined by the length of hospitalisation for the infants and how much preterm they were. The use of probiotics rendered the gut microbiota and resistome of extremely preterm infants more alike to term infants on day 7 and partially restored the loss of species interconnectivity and stability associated with preterm delivery. Finally, colonisation with Escherichia coli was associated with the highest number of antibiotic-resistance genes in the infant microbiomes, followed by Klebsiella pneumoniae and Klebsiella aerogenes.

Being born very preterm, along with prolonged hospitalisation and frequent antibiotic use alters early life resistome and mobilome, leading to an increased gut carriage of antibiotic resistance genes and mobile genetic elements. On the other hand, the effect of probiotics was not unidirectional. Probiotics decreased resistome burden, but at the same time the bacterial strains in the probiotics appear to promote the activity of mobile genetic elements. Here, further study of the gut microbiota is necessary to be able to design strategies aiming to lower disease risk in vulnerable preterm infants.

As mentioned, this study was a collaboration with Veronika Pettersen‘s group in Tromsø, particularly Ahmed Bargheet, who have done a fabulous job on the bioinformatics and analysis of this study. I hope that we will continue this collaboration in the future (first step will be me visting Tromsø again in June!) This also continues a nice little “sidetrack” of the group’s research into the early life microbiome – previously represented by the work of Katariina Pärnänen (3) and Tove Wikström‘s vaginal microbiome study (4), which is a very interesting and relevant subject in terms of both medicine and microbial ecology. We are also setting up new collaborations in this area, so I hope that more will come out of this track in the next couple of years.

Finally, thank you Veronika for inviting me to participate in this great project!

References

1. Bargheet A, Klingenberg C, Esaiassen E, Hjerde E, Cavanagh JP, Bengtsson-Palme J, Pettersen VK: Development of early life gut resistome and mobilome across gestational ages and microbiota-modifying treatments. eBio Medicine, 92, 104613 (2023). doi: 10.1016/j.ebiom.2023.104613
2. Esaiassen E, Hjerde E, Cavanagh JP, Pedersen T, Andresen JH, Rettedal SI, Støen R, Nakstad B, Willassen NP, Klingenberg C: Effects of Probiotic Supplementation on the Gut Microbiota and Antibiotic Resistome Development in Preterm Infants. Frontiers in Pediatrics, 16, 6, 347 (2018). doi: 10.3389/fped.2018.00347
3. 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
4. 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

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

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!

Last week, I published 13 (!!) papers in the EFSA Journal on how to assess concentrations of antibiotics that could select for antibiotic resistance in animal feed (1-13). Or, well, you could also look at it as that the EFSA Biohaz panel that I have been a part of for more than two years published our final 13-part report.

Regardless of how you view it, this set of papers have two main takeaways:

1. We present a method to establish Predicted Minimal Selective Concentrations (PMSCs) for antibiotics. This method uses a combination of Dan Andersson’s approach to MSCs (14) and the method I published with Joakim Larsson around five years ago to establish predicted no-effect concentrations (PNECs) for antibiotics based on MIC data (15). The combination is a powerful (but very cautious) tool to estimate minimal selective concentrations for antibiotics (1), and we have subsequently applied this method to animal feed contamination with antibiotics, but…
2. There is way too little data to establish PMSCs for most antibiotics with any certainty. Really, the lack of data is so bad that for many of the antibiotic classes we could not make a reasonable assessment. Thus the main conclusion might be that we need a lot more data on how low concentrations of antibiotics that select for antibiotic resistance, both in laboratory systems and in more realistic settings.

References

1. EFSA Panel on Biological Hazards (BIOHAZ)*, Allende A, Koutsoumanis K, Alvarez-Ordóñez A, Bolton D, Bover-Cid S, Chemaly M, Davies R, De Cesare A, Herman L, Hilbert F, Lindqvist R, Nauta M, Ru G, Simmons M, Skandamis P, Suffredini E, Andersson DI, Bampidis V, Bengtsson-Palme J, Bouchard D, Ferran A, Kouba M, López Puente S, López-Alonso M, Saxmose Nielsen S, Pechová A, Petkova M, Girault S, Broglia A, Guerra B, Lorenzo Innocenti M, Liébana E, López-Gálvez G, Manini P, Stella P, Peixe L: Maximum levels of cross-contamination for 24 antimicrobial active substances in non-target feed. Part 1: Methodology, general data gaps and uncertainties. EFSA Journal, 19, 10 (2021). doi: 10.2903/j.efsa.2021.6852 [Paper link]
2. EFSA Panel on Biological Hazards (BIOHAZ)*, Allende A, Koutsoumanis K, Alvarez-Ordóñez A, Bolton D, Bover-Cid S, Chemaly M, Davies R, De Cesare A, Herman L, Hilbert F, Lindqvist R, Nauta M, Ru G, Simmons M, Skandamis P, Suffredini E, Andersson DI, Bampidis V, Bengtsson-Palme J, Bouchard D, Ferran A, Kouba M, López Puente S, López-Alonso M, Saxmose Nielsen S, Pechová A, Petkova M, Girault S, Broglia A, Guerra B, Lorenzo Innocenti M, Liébana E, López-Gálvez G, Manini P, Stella P, Peixe L: Maximum levels of cross-contamination for 24 antimicrobial active substances in non-target feed. Part 2: Aminoglycosides/aminocyclitols: apramycin, paromomycin, neomycin and spectinomycin. EFSA Journal, 19, 10 (2021). doi: 10.2903/j.efsa.2021.6853 [Paper link]
3. EFSA Panel on Biological Hazards (BIOHAZ)*, Allende A, Koutsoumanis K, Alvarez-Ordóñez A, Bolton D, Bover-Cid S, Chemaly M, Davies R, De Cesare A, Herman L, Hilbert F, Lindqvist R, Nauta M, Ru G, Simmons M, Skandamis P, Suffredini E, Andersson DI, Bampidis V, Bengtsson-Palme J, Bouchard D, Ferran A, Kouba M, López Puente S, López-Alonso M, Saxmose Nielsen S, Pechová A, Petkova M, Girault S, Broglia A, Guerra B, Lorenzo Innocenti M, Liébana E, López-Gálvez G, Manini P, Stella P, Peixe L: Maximum levels of cross-contamination for 24 antimicrobial active substances in non-target feed. Part 3: Amprolium. EFSA Journal, 19, 10 (2021). doi: 10.2903/j.efsa.2021.6854 [Paper link]
4. EFSA Panel on Biological Hazards (BIOHAZ)*, Allende A, Koutsoumanis K, Alvarez-Ordóñez A, Bolton D, Bover-Cid S, Chemaly M, Davies R, De Cesare A, Herman L, Hilbert F, Lindqvist R, Nauta M, Ru G, Simmons M, Skandamis P, Suffredini E, Andersson DI, Bampidis V, Bengtsson-Palme J, Bouchard D, Ferran A, Kouba M, López Puente S, López-Alonso M, Saxmose Nielsen S, Pechová A, Petkova M, Girault S, Broglia A, Guerra B, Lorenzo Innocenti M, Liébana E, López-Gálvez G, Manini P, Stella P, Peixe L: Maximum levels of cross-contamination for 24 antimicrobial active substances in non-target feed. Part 4: ß-Lactams: amoxicillin and penicillin. EFSA Journal, 19, 10 (2021). doi: 10.2903/j.efsa.2021.6855 [Paper link]
5. EFSA Panel on Biological Hazards (BIOHAZ)*, Allende A, Koutsoumanis K, Alvarez-Ordóñez A, Bolton D, Bover-Cid S, Chemaly M, Davies R, De Cesare A, Herman L, Hilbert F, Lindqvist R, Nauta M, Ru G, Simmons M, Skandamis P, Suffredini E, Andersson DI, Bampidis V, Bengtsson-Palme J, Bouchard D, Ferran A, Kouba M, López Puente S, López-Alonso M, Saxmose Nielsen S, Pechová A, Petkova M, Girault S, Broglia A, Guerra B, Lorenzo Innocenti M, Liébana E, López-Gálvez G, Manini P, Stella P, Peixe L: Maximum levels of cross-contamination for 24 antimicrobial active substances in non-target feed. Part 5: Lincosamides: lincomycin. EFSA Journal, 19, 10 (2021). doi: 10.2903/j.efsa.2021.6856 [Paper link]
6. EFSA Panel on Biological Hazards (BIOHAZ)*, Allende A, Koutsoumanis K, Alvarez-Ordóñez A, Bolton D, Bover-Cid S, Chemaly M, Davies R, De Cesare A, Herman L, Hilbert F, Lindqvist R, Nauta M, Ru G, Simmons M, Skandamis P, Suffredini E, Andersson DI, Bampidis V, Bengtsson-Palme J, Bouchard D, Ferran A, Kouba M, López Puente S, López-Alonso M, Saxmose Nielsen S, Pechová A, Petkova M, Girault S, Broglia A, Guerra B, Lorenzo Innocenti M, Liébana E, López-Gálvez G, Manini P, Stella P, Peixe L: Maximum levels of cross-contamination for 24 antimicrobial active substances in non-target feed. Part 6: Macrolides: tilmicosin, tylosin and tylvalosin. EFSA Journal, 19, 10 (2021). doi: 10.2903/j.efsa.2021.6858 [Paper link]
7. EFSA Panel on Biological Hazards (BIOHAZ)*, Allende A, Koutsoumanis K, Alvarez-Ordóñez A, Bolton D, Bover-Cid S, Chemaly M, Davies R, De Cesare A, Herman L, Hilbert F, Lindqvist R, Nauta M, Ru G, Simmons M, Skandamis P, Suffredini E, Andersson DI, Bampidis V, Bengtsson-Palme J, Bouchard D, Ferran A, Kouba M, López Puente S, López-Alonso M, Saxmose Nielsen S, Pechová A, Petkova M, Girault S, Broglia A, Guerra B, Lorenzo Innocenti M, Liébana E, López-Gálvez G, Manini P, Stella P, Peixe L: Maximum levels of cross-contamination for 24 antimicrobial active substances in non-target feed. Part 7: Amphenicols: florfenicol and thiamphenicol. EFSA Journal, 19, 10 (2021). doi: 10.2903/j.efsa.2021.6859 [Paper link]
8. EFSA Panel on Biological Hazards (BIOHAZ)*, Allende A, Koutsoumanis K, Alvarez-Ordóñez A, Bolton D, Bover-Cid S, Chemaly M, Davies R, De Cesare A, Herman L, Hilbert F, Lindqvist R, Nauta M, Ru G, Simmons M, Skandamis P, Suffredini E, Andersson DI, Bampidis V, Bengtsson-Palme J, Bouchard D, Ferran A, Kouba M, López Puente S, López-Alonso M, Saxmose Nielsen S, Pechová A, Petkova M, Girault S, Broglia A, Guerra B, Lorenzo Innocenti M, Liébana E, López-Gálvez G, Manini P, Stella P, Peixe L: Maximum levels of cross-contamination for 24 antimicrobial active substances in non-target feed. Part 8: Pleuromutilins: tiamulin and valnemulin. EFSA Journal, 19, 10 (2021). doi: 10.2903/j.efsa.2021.6860 [Paper link]
9. EFSA Panel on Biological Hazards (BIOHAZ)*, Allende A, Koutsoumanis K, Alvarez-Ordóñez A, Bolton D, Bover-Cid S, Chemaly M, Davies R, De Cesare A, Herman L, Hilbert F, Lindqvist R, Nauta M, Ru G, Simmons M, Skandamis P, Suffredini E, Andersson DI, Bampidis V, Bengtsson-Palme J, Bouchard D, Ferran A, Kouba M, López Puente S, López-Alonso M, Saxmose Nielsen S, Pechová A, Petkova M, Girault S, Broglia A, Guerra B, Lorenzo Innocenti M, Liébana E, López-Gálvez G, Manini P, Stella P, Peixe L: Maximum levels of cross-contamination for 24 antimicrobial active substances in non-target feed. Part 9: Polymyxins: colistin. EFSA Journal, 19, 10 (2021). doi: 10.2903/j.efsa.2021.6861 [Paper link]
10. EFSA Panel on Biological Hazards (BIOHAZ)*, Allende A, Koutsoumanis K, Alvarez-Ordóñez A, Bolton D, Bover-Cid S, Chemaly M, Davies R, De Cesare A, Herman L, Hilbert F, Lindqvist R, Nauta M, Ru G, Simmons M, Skandamis P, Suffredini E, Andersson DI, Bampidis V, Bengtsson-Palme J, Bouchard D, Ferran A, Kouba M, López Puente S, López-Alonso M, Saxmose Nielsen S, Pechová A, Petkova M, Girault S, Broglia A, Guerra B, Lorenzo Innocenti M, Liébana E, López-Gálvez G, Manini P, Stella P, Peixe L: Maximum levels of cross-contamination for 24 antimicrobial active substances in non-target feed. Part 10: Quinolones: flumequine and oxolinic acid. EFSA Journal, 19, 10 (2021). doi: 10.2903/j.efsa.2021.6862 [Paper link]
11. EFSA Panel on Biological Hazards (BIOHAZ)*, Allende A, Koutsoumanis K, Alvarez-Ordóñez A, Bolton D, Bover-Cid S, Chemaly M, Davies R, De Cesare A, Herman L, Hilbert F, Lindqvist R, Nauta M, Ru G, Simmons M, Skandamis P, Suffredini E, Andersson DI, Bampidis V, Bengtsson-Palme J, Bouchard D, Ferran A, Kouba M, López Puente S, López-Alonso M, Saxmose Nielsen S, Pechová A, Petkova M, Girault S, Broglia A, Guerra B, Lorenzo Innocenti M, Liébana E, López-Gálvez G, Manini P, Stella P, Peixe L: Maximum levels of cross-contamination for 24 antimicrobial active substances in non-target feed. Part 11: Sulfonamides. EFSA Journal, 19, 10 (2021). doi: 10.2903/j.efsa.2021.6863 [Paper link]
12. EFSA Panel on Biological Hazards (BIOHAZ)*, Allende A, Koutsoumanis K, Alvarez-Ordóñez A, Bolton D, Bover-Cid S, Chemaly M, Davies R, De Cesare A, Herman L, Hilbert F, Lindqvist R, Nauta M, Ru G, Simmons M, Skandamis P, Suffredini E, Andersson DI, Bampidis V, Bengtsson-Palme J, Bouchard D, Ferran A, Kouba M, López Puente S, López-Alonso M, Saxmose Nielsen S, Pechová A, Petkova M, Girault S, Broglia A, Guerra B, Lorenzo Innocenti M, Liébana E, López-Gálvez G, Manini P, Stella P, Peixe L: Maximum levels of cross-contamination for 24 antimicrobial active substances in non-target feed. Part 12: Tetracycline, chlortetracycline, oxytetracycline, and doxycycline. EFSA Journal, 19, 10 (2021). doi: 10.2903/j.efsa.2021.6864[Paper link]
13. EFSA Panel on Biological Hazards (BIOHAZ)*, Allende A, Koutsoumanis K, Alvarez-Ordóñez A, Bolton D, Bover-Cid S, Chemaly M, Davies R, De Cesare A, Herman L, Hilbert F, Lindqvist R, Nauta M, Ru G, Simmons M, Skandamis P, Suffredini E, Andersson DI, Bampidis V, Bengtsson-Palme J, Bouchard D, Ferran A, Kouba M, López Puente S, López-Alonso M, Saxmose Nielsen S, Pechová A, Petkova M, Girault S, Broglia A, Guerra B, Lorenzo Innocenti M, Liébana E, López-Gálvez G, Manini P, Stella P, Peixe L: Maximum levels of cross-contamination for 24 antimicrobial active substances in non-target feed. Part 13: Trimethoprim. EFSA Journal, 19, 10 (2021). doi: 10.2903/j.efsa.2021.6865 [Paper link]
14. Gullberg E, Cao S, Berg OG, Ilbäck C, Sandegren L, Hughes D, et al.: Selection of resistant bacteria at very low antibiotic concentrations. PLoS Pathogens 7, e1002158 (2011). doi: 10.1371/journal.ppat.1002158
15. Bengtsson-Palme J, Larsson DGJ: Concentrations of antibiotics predicted to select for resistant bacteria: Proposed limits for environmental regulation. Environment International, 86, 140-149 (2016). doi: 10.1016/j.envint.2015.10.015 [Paper link]

We are hiring a PhD student to work with interactions between the bacteria in human and environmental microbiomes that are important for community stability and resilience to being colonized by unwanted bacteria (including pathogens). The project seeks to unearth which environmental and genetic factors that are important determinants of bacterial invasiveness and community stability. You can read more at our Open Positions page.

We are looking for a candidate with experience with both bioinformatics and experimental microbiology. Previous experience with microbial communities is a plus, but not a must, as is work with human cell lines.

The project is fully funded by a grant from the Swedish Research Council and the position is planned for 4.5 years, with 4 years of research and course work and half a year of teaching.

If you feel that you are the right person for this position, you can apply here. We look forward to your application! The deadline for applications is October 21.

I am very happy to share the news that our starting grant application to the Swedish Research Council has been granted 3.3 million SEK of funding for four years! This is fantastic news, as it allows us to further explore the interactions between bacteria in the human microbiome that are important for community stability and resilience to being colonized by pathogens. In the granted project, we will investigate environmental and genetic factors that are important for bacterial invasiveness and community stability in the human gastrointestinal tract.

Within the scope of the project, we will establish model bacterial communities and experimental systems for the human stomach and intestine. We will then investigate how disturbances, such as antibiotic exposure, change the interactions in these microbial communities and their long-term stability. Finally, we aim to identify genes that contribute to successful bacterial colonization or resilience to invasion of established communities in the human microbiome.

Aside from myself, Prof. Sara Lindén and Dr. Kaisa Thorell from the University of Gothenburg as well as Prof. Ed Moore at the university’s Culture Collection will be involved in this project in different ways. We will also collaborate with my former postdoc supervisor Prof. Jo Handelsman as well as Dr. Ophelia Venturelli at the University of Wisconsin-Madison. Finally, we will also collaborate with Dr. Åsa Sjöling at the Karolinska Institute. I look forward to work with you all over the coming four years! A big thanks to the Swedish Research Council for believing in this research and investing in making it happen!

I am very happy to share the news that I have been awarded with the Gothenburg Society of Medicine and the Sahlgrenska Academy’s prize to young researchers for our research on the effects of antibiotics on bacteria, including, of course, antibiotic resistance.

I am incredibly honoured by being selected for this award. I am also thrilled with that the Gothenburg Society of Medicine, which is a society mostly for medical doctors, sees the value in our broad, one-health, take on antibiotic resistance as well as other effect that antibiotics may have on microbes, both in the human body and in the environment. The recognition of antibiotic resistance as a one-health problem with solutions both within and outside of the typical medical setting is instrumental for our ability to curb future resistance development.

The award ceremony will take place in connection with the Gothenburg Society of Medicine’s closing meeting on 2 December, where I will present our research together with the senior awardee Professor Claes Ohlsson, who is awarded for his groundbreaking research on osteoporosis.

For a bit more than a year, I have been part of an EFSA panel on biological hazards on cross contamination with antibiotic substances in animal feed. This week the panel has launched an open consultation on sections of the draft scientific opinion, including the proposed methodology and the data gaps identified. Anyone who are interested can submit written comments before 18 November 2020, and the full information can be found at the EFSA website.