Microbiology, Metagenomics and Bioinformatics

Johan Bengtsson-Palme, University of Gothenburg | Wisconsin Institute for Discovery

Browsing Posts tagged Pollutants

Yesterday was an intensive day for typesetters apparently, since they put two of my papers online on the same day. This second paper was published in Environment International, and focuses on predicting minimal selective concentrations for all antibiotics present in the EUCAST database (1).

Today (well, up until yesterday at least), we have virtually no knowledge of which environmental concentrations that can exert a selection pressure for antibiotic resistant bacteria. However, experimentally determining minimal selective concentrations (MSCs) in complex ecosystems would involve immense efforts if done for all antibiotics. Therefore, efforts to theoretically determine MSCs for different antibiotics have been suggested (2,3). In this paper we therefore estimate upper boundaries for selective concentrations for all antibiotics in the EUCAST database, based on the assumption that selective concentrations a priori must be lower than those completely inhibiting growth. Data on Minimal Inhibitory Concentrations (MICs) were obtained for 122 antibiotics and antibiotics combinations, the lowest observed MICs were identified for each of those across all tested species, and to compensate for limited species coverage, we adjusted the lowest MICs for the number of tested species. We finally assessed Predicted No Effect Concentrations (PNECs) for resistance selection using an assessment factor of 10 to account for the differences between MICs and MSCs. Since we found that the link between taxonomic similarity between species and lowest MIC was weak, we have not compensated for the taxonomic diversity that each antibiotic was tested against – only for limited number of species tested. In most cases, our PNECs for selection of resistance were below available PNECs for ecotoxicological effects retrieved from FASS. Also, concentrations predicted to be selective have, for some antibiotics, been detected in regular sewage treatment plants (4), and are greatly exceeded in environments polluted by pharmaceutical pollution (5-7), often with drastic consequences in terms of resistance gene enrichments (8-10). This is a central issue since in principle a transfer event of a novel resistance determinant from an environmental bacteria to an (opportunistic) human pathogen only need to occur once to become a clinical problem (11). Once established, the gene could then spread through human activities, such as trade and travel (7,13). Importantly, this paper:

The paper is available under open access here. We hope, and believe, that the data will be of great use in environmental risk assessments, in efforts by industries, regulatory agencies or purchasers of medicines to define acceptable environmental emissions of antibiotics, in the implementation of environmental monitoring programs, for directing mitigations, and for prioritizing future studies on environmental antibiotic resistance.

References:

  1. 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]
  2. Ågerstrand M, Berg C, Björlenius B, Breitholtz M, Brunstrom B, Fick J, Gunnarsson L, Larsson DGJ, Sumpter JP, Tysklind M, Rudén C: Improving environmental risk assessment of human pharmaceuticals. Environmental Science and Technology (2015). doi:10.1021/acs.est.5b00302
  3. Tello A, Austin B, Telfer TC: Selective pressure of antibiotic pollution on bacteria of importance to public health. Environmental Health Perspectives, 120, 1100–1106 (2012). doi:10.1289/ehp.1104650
  4. Michael I, Rizzo L, McArdell CS, Manaia CM, Merlin C, Schwartz T, Dagot C, Fatta-Kassinos D: Urban wastewater treatment plants as hotspots for the release of antibiotics in the environment: a review. Water Research, 47, 957–995 (2013). doi:10.1016/j.watres.2012.11.027
  5. Larsson DGJ, de Pedro C, Paxeus N: Effluent from drug manufactures contains extremely high levels of pharmaceuticals. Journal of Hazardous Materials, 148, 751–755 (2007). doi:10.1016/j.jhazmat.2007.07.008
  6. Fick J, Söderström H, Lindberg RH, Phan C, Tysklind M, Larsson DGJ: Contamination of surface, ground, and drinking water from pharmaceutical production. Environmental Toxicology and Chemistry, 28, 2522–2527 (2009). doi:10.1897/09-073.1
  7. Larsson DGJ: Pollution from drug manufacturing: review and perspectives. Philosophical Transactions of the Royal Society London, Series B Biological Sciences, 369 (2014). doi:10.1098/rstb.2013.0571
  8. Bengtsson-Palme J, Boulund F, Fick J, Kristiansson E, Larsson DGJ: Shotgun metagenomics reveals a wide array of antibiotic resistance genes and mobile elements in a polluted lake in India. Frontiers in Microbiology, Volume 5, Issue 648 (2014). doi: 10.3389/fmicb.2014.00648 [Paper link]
  9. Kristiansson E, Fick J, Janzon A, Grabic R, Rutgersson C, Weijdegård B, Söderström H, Larsson DGJ: Pyrosequencing of antibiotic-contaminated river sediments reveals high levels of resistance and gene transfer elements. PLoS ONE, Volume 6, e17038 (2011). doi:10.1371/journal.pone.0017038.
  10. Marathe NP, Regina VR, Walujkar SA, Charan SS, Moore ERB, Larsson DGJ, Shouche YS: A Treatment Plant Receiving Waste Water from Multiple Bulk Drug Manufacturers Is a Reservoir for Highly Multi-Drug Resistant Integron-Bearing Bacteria. PLoS ONE, Volume 8, e77310 (2013). doi:10.1371/journal.pone.0077310
  11. Bengtsson-Palme J, Larsson DGJAntibiotic resistance genes in the environment: prioritizing risks. Nature Reviews Microbiology, 13, 369 (2015). doi: 10.1038/nrmicro3399-c1 [Paper link]
  12. Bengtsson-Palme J, Angelin M, Huss M, Kjellqvist S, Kristiansson E, Palmgren H, Larsson DGJ, Johansson A: The human gut microbiome as a transporter of antibiotic resistance genes between continents. Antimicrobial Agents and Chemotherapy, 59, 10, 6551-6560 (2015). doi: 10.1128/AAC.00933-15 [Paper link]

I am very happy to announce that our paper on the metagenomes of periphyton communities (1) have been accepted in Frontiers in Microbiology (Aquatic Microbiology section). This project has been one of my longest running, as it started as my master thesis in 2010 and has gone through several metamorphoses before hitting its final form.

Briefly, our main findings are that:

  1. Periphyton communities harbor an extraordinary diversity of organisms, including viruses, bacteria, algae, fungi, protozoans and metazoans
  2. Bacteria are by far the most abundant
  3. We find functional indicators of the biofilm form of life in periphyton involve genes coding for enzymes that catalyze the production and degradation of extracellular polymeric substances
  4. Genes encoding enzymes that participate in anaerobic pathways are found in the biofilms suggesting that anaerobic or low-oxygen micro-zones within the biofilms exist

Most of this work has been carried out by my colleague Kemal Sanli, who have been doing a wonderful job pulling this together, with the help of Henrik Nilsson and Martin Eriksson. It also deserves to be noted that this work was the starting point for the Metaxa software (2,3), which recently reached version 2.1.1.

References

  1. Sanli K, Bengtsson-Palme J, Nilsson RH, Kristiansson E, Alm Rosenblad M, Blanck H, Eriksson KM: Metagenomic sequencing of marine periphyton: Taxonomic and functional insights into biofilm communities. Frontiers in Microbiology, 6, 1192 (2015). doi: 10.3389/fmicb.2015.01192 [Paper link]
  2. Bengtsson J, Eriksson KM, Hartmann M, Wang Z, Shenoy BD, Grelet G, Abarenkov K, Petri A, Alm Rosenblad M, Nilsson RH: Metaxa: A software tool for automated detection and discrimination among ribosomal small subunit (12S/16S/18S) sequences of archaea, bacteria, eukaryotes, mitochondria, and chloroplasts in metagenomes and environmental sequencing datasets. Antonie van Leeuwenhoek, 100, 3, 471-475 (2011). doi:10.1007/s10482-011-9598-6. [Paper link]
  3. Bengtsson-Palme J, Hartmann M, Eriksson KM, Pal C, Thorell K, Larsson DGJ, Nilsson RH: Metaxa2: Improved identification and taxonomic classification of small and large subunit rRNA in metagenomic data. Molecular Ecology Resources, 15, 6, 1403–1414 (2015). doi: 10.1111/1755-0998.12399 [Paper link]

A couple of days ago a paper was published in Environmental Sciences Europe summarizing the EU report on effect-based tools for use in toxicology in the aquatic environment I have been involved in (1). This report was officially published last spring (2), and can be found here, with the annex available on the European Commission document website. My contribution to the paper was, as with the report, in the genomics and metagenomics section. The paper briefly presents modern bioassays, biomarkers and ecological methods that can be used for aquatic monitoring of the environment.

References:

  1. Wernersson A-S, Carere M, Maggi C, Tusil P, Soldan P, James A, Sanchez W, Dulio V, Broeg K, Reifferscheid G, Buchinger S, Maas H, Van Der Grinten E, O’Toole S, Ausili A, Manfra L, Marziali L, Polesello S, Lacchetti I, Mancini L, Lilja K, Linderoth M, Lundeberg T, Fjällborg B, Porsbring T, Larsson DGJ, Bengtsson-Palme J, Förlin L, Kienle C, Kunz P, Vermeirssen E, Werner I, Robinson CD, Lyons B, Katsiadaki I, Whalley C, den Haan K, Messiaen M, Clayton H, Lettieri T, Negrão Carvalho R, Gawlik BM, Hollert H, Di Paolo C, Brack W. Kammann U, Kase R: The European technical report on aquatic effect-based monitoring tools under the water framework directive. Environmental Sciences Europe, 27, 7 (2015). doi: 10.1186/s12302-015-0039-4 [Paper link]
  2. Wernersson A-S, Carere M, Maggi C, Tusil P, Soldan P, James A, Sanchez W, Broeg K, Kammann U, Reifferscheid G, Buchinger S, Maas H, Van Der Grinten E, Ausili A, Manfra L, Marziali L, Polesello S, Lacchetti I, Mancini L, Lilja K, Linderoth M, Lundeberg T, Fjällborg B, Porsbring T, Larsson DGJ, Bengtsson-Palme J, Förlin L, Kase R, Kienle C, Kunz P, Vermeirssen E, Werner I, Robinson CD, Lyons B, Katsiadaki I, Whalley C, den Haan K, Messiaen M, Clayton H, Lettieri T, Negrão Carvalho R, Gawlik BM, Dulio V, Hollert H, Di Paolo C, Brack W (2014). Technical Report on Aquatic Effect-Based Monitoring Tools. European Commission. Technical Report 2014-077, Office for Official Publications of European Communities, ISBN: 978-92-79-35787-9. doi:10.2779/7260

Our paper describing the bacterial community of a polluted lake in India has now been typeset and appears in its final form in Frontiers in Microbiology. If I may say so, I think that the paper turned out to be very goodlooking and it is indeed nice to finally see it in print. The paper describes an unprecedented diversity and abundance of antibiotic resistance genes and genes enabling transfer of DNA between bacteria. We also describe a range of potential novel plasmids from the lake. Finally, the paper briefly describes a new approach to targeted assembly of metagenomic data — TriMetAss — which can be downloaded here.

Reference:
Bengtsson-Palme J, Boulund F, Fick J, Kristiansson E, Larsson DGJ: Shotgun metagenomics reveals a wide array of antibiotic resistance genes and mobile elements in a polluted lake in India. Frontiers in Microbiology, 5, 648 (2014). doi: 10.3389/fmicb.2014.00648

The first work in which I have employed metagenomics to investigate antibiotic resistance has been accepted in Frontiers in Microbiology, and is (at the time of writing) available as a provisional PDF. In the paper (1), which is co-authored by Fredrik Boulund, Jerker Fick, Erik Kristiansson and Joakim Larsson, we have used shotgun metagenomic sequencing of an Indian lake polluted by dumping of waste from pharmaceutical production. We used this data to describe the diversity of antibiotic resistance genes and the genetic context of those, to try to predict their genetic transferability. We found resistance genes against essentially every major class of antibiotics, as well as large abundances of genes responsible for mobilization of genetic material. Resistance genes were estimated to be 7000 times more abundant in the polluted lake than in a Swedish lake included for comparison, where only eight resistance genes were found. The abundances of resistance genes have previously only been matched by river sediment subject to pollution from pharmaceutical production (2). In addition, we describe twenty-six known and twenty-one putative novel plasmids from the Indian lake metagenome, indicating that there is a large potential for horizontal gene transfer through conjugation. Based on the wide range and high abundance of known resistance factors detected, we believe that it is plausible that novel resistance genes are also present in the lake. We conclude that environments polluted with waste from antibiotic manufacturing could be important reservoirs for mobile antibiotic resistance genes. This work further highlights previous findings that pharmaceutical production settings could provide sufficient selection pressure from antibiotics (3) to drive the development of multi-resistant bacteria (4,5), resistance which may ultimately end up in pathogenic species (6,7). The paper can be read in its entirety here.

References:

  1. Bengtsson-Palme J, Boulund F, Fick J, Kristiansson E, Larsson DGJ: Shotgun metagenomics reveals a wide array of antibiotic resistance genes and mobile elements in a polluted lake in India. Frontiers in Microbiology, Volume 5, Issue 648 (2014). doi: 10.3389/fmicb.2014.00648
  2. Kristiansson E, Fick J, Janzon A, Grabic R, Rutgersson C, Weijdegård B, Söderström H, Larsson DGJ: Pyrosequencing of antibiotic-contaminated river sediments reveals high levels of resistance and gene transfer elements. PLoS ONE, Volume 6, e17038 (2011). doi:10.1371/journal.pone.0017038.
  3. Larsson DGJ, de Pedro C, Paxeus N: Effluent from drug manufactures contains extremely high levels of pharmaceuticals. J Hazard Mater, Volume 148, 751–755 (2007). doi:10.1016/j.jhazmat.2007.07.008
  4. Marathe NP, Regina VR, Walujkar SA, Charan SS, Moore ERB, Larsson DGJ, Shouche YS: A Treatment Plant Receiving Waste Water from Multiple Bulk Drug Manufacturers Is a Reservoir for Highly Multi-Drug Resistant Integron-Bearing Bacteria. PLoS ONE, Volume 8, e77310 (2013). doi:10.1371/journal.pone.0077310
  5. Johnning A, Moore ERB, Svensson-Stadler L, Shouche YS, Larsson DGJ, Kristiansson E: Acquired genetic mechanisms of a multiresistant bacterium isolated from a treatment plant receiving wastewater from antibiotic production. Appl Environ Microbiol, Volume 79, 7256–7263 (2013). doi:10.1128/AEM.02141-13
  6. Pruden A, Larsson DGJ, Amézquita A, Collignon P, Brandt KK, Graham DW, Lazorchak JM, Suzuki S, Silley P, Snape JR., et al.: Management options for reducing the release of antibiotics and antibiotic resistance genes to the environment. Environ Health Perspect, Volume 121, 878–885 (2013). doi:10.1289/ehp.1206446
  7. Finley RL, Collignon P, Larsson DGJ, McEwen SA, Li X-Z, Gaze WH, Reid-Smith R, Timinouni M, Graham DW, Topp E: The scourge of antibiotic resistance: the important role of the environment. Clin Infect Dis, Volume 57, 704–710 (2013). doi:10.1093/cid/cit355

I just got word from BMC Genomics that my most recent paper has just been published (in provisional form; we still have not seen the edited proofs). In this paper (1), which I have co-authored with Anders Blomberg, Magnus Alm Rosenblad and Mikael Molin, we utilize metagenomic data from the GOS-expedition (2) together with fully sequenced bacterial genomes to show that:

  1. Detoxification genes in general are underrepresented in marine planktonic bacteria
  2. Surprisingly, the detoxification that show a differential distribution are more abundant in open ocean water than closer to the coast
  3. Peroxidases and peroxiredoxins seem to be the main line of defense against oxidative stress for bacteria in the marine milieu, rather than e.g. catalases
  4. The abundance of detoxification genes does not seem to increase with estimated pollution.

From this we conclude that other selective pressures than pollution likely play the largest role in shaping marine planktonic bacterial communities, such as for example nutrient limitations. This suggests substantial streamlining of gene copy number and genome sizes, in line with observations made in previous studies (3). Along the same lines, our findings indicate that the majority of marine bacteria would have a low capacity to adapt to increased pollution, which is relevant as large amounts of human pollutants and waste end up in the oceans every year. The study exemplifies the use of metagenomics data in ecotoxicology, and how we can examine anthropogenic consequences on life in the sea using approaches derived from genomics. You can read the paper in its entirety here.

References:

  1. Bengtsson-Palme J, Alm Rosenblad M, Molin M, Blomberg A: Metagenomics reveals that detoxification systems are underrepresented in marine bacterial communities. BMC Genomics. Volume 15, Issue 749 (2014). doi: 10.1186/1471-2164-15-749 [Paper link]

  2. Yooseph S, Sutton G, Rusch DB, Halpern AL, Williamson SJ, Remington K, Eisen JA, Heidelberg KB, Manning G, Li W, Jaroszewski L, Cieplak P, Miller CS, Li H, Mashiyama ST, Joachimiak MP, Van Belle C, Chandonia J-M, Soergel DA, Zhai Y, Natarajan K, Lee S, Raphael BJ, Bafna V, Friedman R, Brenner SE, Godzik A, Eisenberg D, Dixon JE, Taylor SS, et al: The Sorcerer II Global Ocean Sampling expedition: expanding the universe of protein families. PLoS Biology. 5:e16 (2007).
  3. Yooseph S, Nealson KH, Rusch DB, McCrow JP, Dupont CL, Kim M, Johnson J, Montgomery R, Ferriera S, Beeson KY, Williamson SJ, Tovchigrechko A, Allen AE, Zeigler LA, Sutton G, Eisenstadt E, Rogers Y-H, Friedman R, Frazier M, Venter JC: Genomic and functional adaptation in surface ocean planktonic prokaryotes. Nature. 468:60–66 (2010).

Because of my previous involvement in a Swedish report on toxicological monitoring using (meta)-genomics tools [1], I also became in a related EU report on effect-based tools for use in toxicology in the aquatic environment. This report has recently been officially published [2], and can be found here, with the annex available on the European Commission document website. My contribution to this report has been in the genomics and metagenomics section (Chapter 7: OMICS techniques), in which I wrote the metagenomics part and contributed to the rest. I personally think this is a quite forward-thinking report, which is nice for a large institution such as the EU.

  1. Länsstyrelsen i Västra Götalands län. (2012). Swedish monitoring of hazardous substances in the aquatic environment (No. 2012:23). (A.-S. Wernersson, Ed.) Current vs required monitoring and potential developments (pp. 1–291). Länsstyrelsen i Västra Götalands län, vattenvårdsenheten.
  2. Wernersson A-S, Carere M, Maggi C, Tusil P, Soldan P, James A, Sanchez W, Broeg K, Kammann U, Reifferscheid G, Buchinger S, Maas H, Van Der Grinten E, Ausili A, Manfra L, Marziali L, Polesello S, Lacchetti I, Mancini L, Lilja K, Linderoth M, Lundeberg T, Fjällborg B, Porsbring T, Larsson DGJ, Bengtsson-Palme J, Förlin L, Kase R, Kienle C, Kunz P, Vermeirssen E, Werner I, Robinson CD, Lyons B, Katsiadaki I, Whalley C, den Haan K, Messiaen M, Clayton H, Lettieri T, Negrão Carvalho R, Gawlik BM, Dulio V, Hollert H, Di Paolo C, Brack W (2014). Technical Report on Aquatic Effect-Based Monitoring Tools. European Commission. Technical Report 2014-077, Office for Official Publications of European Communities, ISBN: 978-92-79-35787-9. doi:10.2779/7260

It seems like our paper on the recently launched database on resistance genes against antibacterial biocides and metals (BacMet) has gone online as an advance access paper in Nucleic Acids Research today. Chandan Pal – the first author of the paper, and one of my close colleagues as well as my roommate at work – has made a tremendous job taking the database from a list of genes and references, to a full-fledged browsable and searchable database with a really nice interface. I have contributed along the process, and wrote the lion’s share of the code for the BacMet-Scan tool that can be downloaded along with the database files.

BacMet is a curated source of bacterial resistance genes against antibacterial biocides and metals. All gene entries included have at least one experimentally confirmed resistance gene with references in scientific literature. However, we have also made a homology-based prediction of genes that are likely to share the same resistance function (the BacMet predicted dataset). We believe that the BacMet database will make it possible to better understand co- and cross-resistance of biocides and metals to antibiotics within bacterial genomes and in complex microbial communities from different environments.

The database can be easily accessed here: http://bacmet.biomedicine.gu.se, and use of the database in scientific work can cite the following paper, which recently appeared in Nucleic Acids Research:

Pal C, Bengtsson-Palme J, Rensing C, Kristiansson E, Larsson DGJ: BacMet: Antibacterial Biocide and Metal Resistance Genes Database. Nucleic Acids Research. Database issue, advance access. doi: 10.1093/nar/gkt1252 [Paper link]

I was recently involved as an adviser in a report by the County Administrative Board in Västra Götaland (Länsstyrelsen) which has now been published [1]. [UPDATE: The PDF link at Länsstyrelsen's page does not seem to work, but leads to another report in Swedish. I have reported this error to the web admin, we'll see what happens. Once again, the PDF seems to work.] The report aims to identify gaps in the current monitoring system of hazardous substances in the Swedish environment. The report deals with effect based monitoring tools and their usefulness for predicting and/or observing effects of hazardous substances in the environment. The overall conclusion of the report is that there are several gaps in both knowledge and techniques, and a need for developing new resources. However, Sweden still has a good potential to adapt the monitoring system to fill the needs. I have been involved in one of the last chapters, describing the use of metagenomics if study ecosystem function (chapter 30.3). For people with an interest in environmental monitoring, the report is an interesting read in its entirety. For those more interested in applications for metagenomics I recommend turning to page 285 and continue to the end of the report (it’s only five pages on metagenomics, so you’ll manage).

  1. Länsstyrelsen i Västra Götalands län. (2012). Swedish monitoring of hazardous substances in the aquatic environment (No. 2012:23). (A.-S. Wernersson, Ed.) Current vs required monitoring and potential developments (pp. 1–291). Länsstyrelsen i Västra Götalands län, vattenvårdsenheten.

Finally I have gotten around to finish my reply to Amy Pruden, who gave me some highly relevant and well-balanced critique of my previous post on antibiotic resistance genes as pollutants, back in early March. Too much came in between, but now I am more or less content with my answer.

First of all I would like to thank Amy for her response to my post on antibiotic resistance genes as pollutants. Her reply is very well thought-through, and her criticism of some of my claims is highly appropriate. For example, I have to agree on that the extracellular DNA pool is vastly uncharacterized, and that my statement on this likely not being a source of resistance transmission is a bit of a stretch. The role of “free-floating” DNA in gene transfer must be further elucidated, and currently we do not really know whether it is important or not; and if so, to what extent it contributes.

However, I still maintain my view that there are problems with considering resistance genes pollutants, mainly because the blurs the line between cause and effect. If we for example consider photosynthetic microbial communities exposed to the photosynthesis inhibitor Irgarol, the communities develop (or acquires) tolerance towards the compound over time (Blanck et al 2009). The tolerance mechanism has been attributed to changes in the psbA gene sequence (Eriksson et al. 2009). If we address this issue from a “resistance-genes-as-pollutants” perspective, would these tolerance-conveying psbA genes be considered pollutants? It would make sense to do so as they are unwanted in weed control circumstances; much like antibiotic resistance genes are unwanted in clinical contexts. It could be argued here that in these microbes such tolerance-associated psbA genes do not cause any harm. But consider for a moment that they did not occur microbes, but in weeds, would they then be considered pollutants? In weeds they would certainly cause (at least economic) harm. Furthermore, say that the tolerance-conveying psbA genes have the ability to spread (which is possible at least in marine settings assisted by phages (Lindell et al 2005)), would that make these tolerance genes pollutants? It is quite of a stretch but as plants can take up genetic material from bacteria (c.f. Clough & Bent 1998, although this is not my area of expertise), there could be a spreading potential to weeds of these tolerance-conveying psbA genes.

What I am trying to say is that if we start viewing antibiotic resistance genes as pollutants per se, instead of looking at the chemicals (likely) causing resistance development, we start blurring the line between cause and effect. Resistance genes in the environment provide resilience to communities (at least to some species – the issue of ecosystem function responses to toxicants is a highly interesting area one as well). However, in this case the resilience itself is the problem, because we think it can spread into human and animal pathogens. But from my point of view, the causes are still use, overuse, misuse and inappropriate release of antibiotics. Therefore, I maintain that we should be careful with pointing out resistance genes by themselves as pollutants – if we do not have very good reasons to do so.

Nevertheless, that does not mean that I think Pruden, and many other prominent authors, are wrong when they refer to resistance genes as pollutants. All I want to point out is that the statement in itself is a bit dangerous, as it might draw attention towards mitigating the effect of pollution, instead of mitigating the source of pollution itself. The persistence of resistance genes in bacterial genomes is alarming (Andersson & Hughes 2011), as it means that removal of selection pressures may have less effect on resistance gene abundance than anticipated. However, the only way I see out of this darkening scenario is to:

  1. Minimize the selection pressure for resistance genes in the clinical setting
  2. Immediately reduce environmental release of antibiotics, both from manufacturing and use. This primarily has to be done using better treatment technologies
  3. Find the routes that enable environmental bacteria to disseminate resistance genes to clinically relevant species and strains – and close them
  4. Develop antibiotics exploiting new mechanisms to eliminate bacteria

Lastly, I would like to thank Amy for taking my critique seriously – I think we agree on a lot more than we differ on, and I look forward to have this discussion in person at some point. I think we both agree that regardless of our standpoint, the terminology used in this context deserves to be discussed. Nevertheless, the terminology is quite unimportant compared to the values that are at stake – our fundamental ability to treat diseases and perform modern health care.

References

  1. Andersson, D.I. & Hughes, D., 2011. Persistence of antibiotic resistance in bacterial populations. FEMS Microbiology Reviews, 35(5), pp.901–911.
  2. Blanck, H., Eriksson, K. M., Grönvall, F., Dahl, B., Guijarro, K. M., Birgersson, G., & Kylin, H. (2009). A retrospective analysis of contamination and periphyton PICT patterns for the antifoulant irgarol 1051, around a small marina on the Swedish west coast. Marine pollution bulletin, 58(2), 230–237. doi:10.1016/j.marpolbul.2008.09.021
  3. Clough, S. J., & Bent, A. F. (1998). Floral dip: a simplified method for Agrobacterium-mediated transformation of Arabidopsis thaliana. The Plant journal : for cell and molecular biology, 16(6), 735–743.
  4. Eriksson, K. M., Clarke, A. K., Franzen, L.-G., Kuylenstierna, M., Martinez, K., & Blanck, H. (2009). Community-level analysis of psbA gene sequences and irgarol tolerance in marine periphyton. Applied and Environmental Microbiology, 75(4), 897–906. doi:10.1128/AEM.01830-08
  5. Lindell, D., Jaffe, J. D., Johnson, Z. I., Church, G. M., & Chisholm, S. W. (2005). Photosynthesis genes in marine viruses yield proteins during host infection. Nature, 438(7064), 86–89. doi:10.1038/nature04111