Tag: Virulence

Last week, FEMS Microbes published our most recent work on the genomes of Escherichia coli in coastal marine sediments from the Helsingborg area in Sweden (1). Part of our sampled area was next to the discharge point of the city’s wastewater treatment plant (WWTP) effluent. We discovered that the E. coli population in these sediment is diverse, containing serotypes typically associated with both humans, livestock and other animals. We also found that virulence genes were more common among the isolates collected closer to the WWTP discharge site. Only one isolate was phenotypically antibiotic resistant, and carried corresponding tetracycline resistance genes on a plasmid. All isolates were halotolerant, growing at 3.5% NaCl. Since most isolates were also good at forming biofilm, this suggests that marine sediments can select for E. coli with increased survival properties and could be a potential reservoir for E. coli that could be spread to humans when the sediments are disturbed. Furthermore, the naturalisation of these E. coli questions it as an indicator for faecal contamination of marine sediments.

The paper is primarily the work of Isabel Erb, Carolina Suarez, and Catherine Paul at Lund University, and they have made a terrific job on this while I have mostly provided some input on the bioinformatics and genomics analyses. The study is a nice example of how genomics analysis could nuance monitoring for pathogens and antibiotic resistance in environments close to human activities. Since these sediments are also closely connected to humans in terms of exposure – the Helsingborg beach is in the neighbouring area – this highlight potential exposure routes for pathogens and antibiotic resistance (2).

The finding of a single antibiotic resistant isolate highlights the issue of comparing between different monitoring methods (2). While a single isolates might be consider a small number, it is really hard to compare if this is outside of the normal range of resistance (3) as measured by, e.g., qPCR. This further points to the importance of standardisation of antibiotic resistance monitoring in the environment, in a way that is both reliable, feasible and economic. That said, it also shows the potential in monitoring, for example, public beaches for pathogens and resistance, and how this could be used to better design and implement mitigation strategies, including the temporary closing of public beaches in contaminated areas. For this to work, however, a better knowledge of the background levels of resistance is required, as we have been working on in the EMBARK program.

References

1. Erb IK, Suarez C, Frank EM, Bengtsson-Palme J, Lindberg E, Paul CJ: Escherichia coli in urban marine sediments: interpreting virulence, biofilm formation, halotolerance and antibiotic resistance to infer contamination or naturalisation. FEMS Microbes (advance article) xtae024 (2024). doi: 10.1093/femsmc/xtae024
2. 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, 178, 108089 (2023). doi: 10.1016/j.envint.2023.108089
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

This is the fifth episode of the Microbiology Lab Pod and has been lying around on my computer almost finished for way too long. It was recorded on September 23, and the bigger-than-ever-before crew (Johan Bengtsson-Palme, Emil Burman, Haveela Kunche, Anna Abramova, Marcus Wenne, Sebastian Wettersten and Mahbuba Lubna Akter) is joined by Fanny Berglund to discuss computational discovery of novel resistance genes. We also discuss antibiotic resistance mechanisms, particularly in Pseudomonas aeruginosa.

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

• 5:30 – Berglund, F., Johnning, A., Larsson, D.G.J., Kristiansson, E., 2020. An updated phylogeny of the metallo-b-lactamases. Journal of Antimicrobial Chemotherapy 7. https://doi.org/10.1093/jac/dkaa392
• 5:45 – Berglund, F., Österlund, T., Boulund, F., Marathe, N.P., Larsson, D.G.J., Kristiansson, E., 2019. Identification and reconstruction of novel antibiotic resistance genes from metagenomes. Microbiome 7, 52. https://doi.org/10.1186/s40168-019-0670-1
• 6:00 – Berglund, F., Marathe, N.P., Österlund, T., Bengtsson-Palme, J., Kotsakis, S., Flach, C.-F., Larsson, D.G.J., Kristiansson, E., 2017. Identification of 76 novel B1 metallo-β-lactamases through large-scale screening of genomic and metagenomic data. Microbiome 5, i29. https://doi.org/10.1186/s40168-017-0353-8
• 6:15 – Boulund, F., Berglund, F., Flach, C.-F., Bengtsson-Palme, J., Marathe, N.P., Larsson, D.G.J., Kristiansson, E., 2017. Computational discovery and functional validation of novel fluoroquinolone resistance genes in public metagenomic data sets. BMC Genomics 18, 438. https://doi.org/10.1186/s12864-017-4064-0
• 37:15 – Crippen, C.S., Jr., M.J.R., Sanchez, S., Szymanski, C.M., 2020. Multidrug Resistant Acinetobacter Isolates Release Resistance Determinants Through Contact-Dependent Killing and Bacteriophage Lysis. Frontiers in Microbiology 11. https://doi.org/10.3389/fmicb.2020.01918
• 52:15 – Leonard, A.F.C., Zhang, L., Balfour, A.J., Garside, R., Hawkey, P.M., Murray, A.K., Ukoumunne, O.C., Gaze, W.H., 2018. Exposure to and colonisation by antibiotic-resistant E. coli in UK coastal water users: Environmental surveillance, exposure assessment, and epidemiological study (Beach Bum Survey). Environment International 114, 326–333. https://doi.org/10.1016/j.envint.2017.11.003
• 53:30 – Bengtsson-Palme, J., Kristiansson, E., Larsson, D.G.J., 2018. Environmental factors influencing the development and spread of antibiotic resistance. FEMS Microbiology Reviews 42, 25. https://doi.org/10.1093/femsre/fux053
• 54:30 – Leonard, A.F.C., Zhang, L., Balfour, A.J., Garside, R., Gaze, W.H., 2015. Human recreational exposure to antibiotic resistant bacteria in coastal bathing waters. Environment International 82, 92–100. https://doi.org/10.1016/j.envint.2015.02.013
• 55:30 – Ahmed, M.N., Abdelsamad, A., Wassermann, T., et al., 2020. The evolutionary trajectories of P. aeruginosa in biofilm and planktonic growth modes exposed to ciprofloxacin: beyond selection of antibiotic resistance. npj Biofilms and Microbiomes 6. https://doi.org/10.1038/s41522-020-00138-8
• 69:30 – Rezzoagli, C., Archetti, M., Mignot, I., Baumgartner, M., Kümmerli, R., 2020. Combining antibiotics with antivirulence compounds can have synergistic effects and reverse selection for antibiotic resistance in Pseudomonas aeruginosa. PLOS Biology 18, e3000805. https://doi.org/10.1371/journal.pbio.3000805
• 79:45 – Allen, R.C., Popat, R., Diggle, S.P., Brown, S.P., 2014. Targeting virulence: can we make evolution-proof drugs? Nature reviews Microbiology 12, 300–308. https://doi.org/10.1038/nrmicro3232
• 80:45 – Köhler, T., Perron, G.G., Buckling, A., van Delden, C., 2010. Quorum Sensing Inhibition Selects for Virulence and Cooperation in Pseudomonas aeruginosa. PLoS Pathogens 6, e1000883. https://doi.org/10.1371/journal.ppat.1000883

The podcast was recorded on September 23, 2020. 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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In the second episode of Microbiology Lab Pod, a crew consisting of Johan Bengtsson-Palme, Emil Burman, Haveela Kunche and Anna Abramova discusses how to identify novel resistance genes with our special guest Marlies Böhm. We also talk about bacterial virulence: how do bacteria become virulent, how do virulence relate to competition, how do bacteria evade the immune system and can we attenuate virulence using fatty acids?

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

• 7:15 – Böhm, M.-E., Razavi, M., Flach, C.-F., Larsson, D.G.J., 2020a. A Novel, Integron-Regulated, Class C β-Lactamase. Antibiotics 9, 123. https://doi.org/10.3390/antibiotics9030123
• 7:15 – Böhm, M.-E., Razavi, M., Marathe, N.P., Flach, C.-F., Larsson, D.G.J., 2020b. Discovery of a novel integron-borne aminoglycoside resistance gene present in clinical pathogens by screening environmental bacterial communities. Microbiome 8. https://doi.org/10.1186/s40168-020-00814-z
• 9:15 – Makowska, N., et al., 2020. Occurrence of integrons and antibiotic resistance genes in cryoconite and ice of Svalbard, Greenland, and the Caucasus glaciers. Science of The Total Environment 716, 137022. https://doi.org/10.1016/j.scitotenv.2020.137022
• 20:45 – Marathe, N.P., et al., 2019. Scandinavium goeteborgense gen. nov., sp. nov., a New Member of the Family Enterobacteriaceae Isolated From a Wound Infection, Carries a Novel Quinolone Resistance Gene Variant. Frontiers in Microbiology 10. https://doi.org/10.3389/fmicb.2019.02511
• 33:45 – Kaito, C., Yoshikai, H., Wakamatsu, A., Miyashita, A., Matsumoto, Y., Fujiyuki, T., Kato, M., Ogura, Y., Hayashi, T., Isogai, T., Sekimizu, K., 2020. Non-pathogenic Escherichia coli acquires virulence by mutating a growth-essential LPS transporter. PLOS Pathogens 16, e1008469. https://doi.org/10.1371/journal.ppat.1008469
• 43:45 – Lories, B., Roberfroid, S., Dieltjens, L., De Coster, D., Foster, K.R., Steenackers, H.P., 2020. Biofilm Bacteria Use Stress Responses to Detect and Respond to Competitors. Current Biology 30, 1231-1244.e4. https://doi.org/10.1016/j.cub.2020.01.065
• 45:45 – Lozano, G.L., Bravo, J.I., Garavito Diago, M.F., Park, H.B., Hurley, A., Peterson, S.B., Stabb, E.V., Crawford, J.M., Broderick, N.A., Handelsman, J., 2019. Introducing THOR, a Model Microbiome for Genetic Dissection of Community Behavior. mBio 10. https://doi.org/10.1128/mBio.02846-18
• 55:45 – Kumar, P., Lee, J.-H., Beyenal, H., Lee, J., 2020. Fatty Acids as Antibiofilm and Antivirulence Agents. Trends in Microbiology. https://doi.org/10.1016/j.tim.2020.03.014
• 60:15 – Gullberg, E., Cao, S., Berg, O.G., Ilbäck, C., Sandegren, L., Hughes, D., Andersson, D.I., 2011. Selection of resistant bacteria at very low antibiotic concentrations. PLoS Pathogens 7, e1002158. https://doi.org/10.1371/journal.ppat.1002158
• 61:15 – Larsson, D.G.J., 2018. Risks of using the natural defence of commensal bacteria as antibiotics call for research and regulation. International Journal of Antimicrobial Agents 51, 277–278. https://doi.org/10.1016/j.ijantimicag.2017.12.018
• 65:15 – Lone, A.G., Bankhead, T., 2020. The Borrelia burgdorferi VlsE Lipoprotein Prevents Antibody Binding to an Arthritis-Related Surface Antigen. Cell Reports 30, 3663-3670.e5. https://doi.org/10.1016/j.celrep.2020.02.081

The podcast was recorded on May 7, 2020. 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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It seriously worries me that a number of indications recently have pointed to that the heavy use of antibiotics does not only drive antibiotic resistance development, but also the development towards more virulent and aggressive strains of pathogenic bacteria. First, the genome sequencing of the E. coli strain that caused the EHEC outbreak in Germany in May revealed not only antibiotic resistance genes, but also is also able to make Shiga toxin, which is causes the severe diarrhoea and kidney damage related to the haemolytic uremic syndrome (HUS). The genes encoding the Shiga toxin are not originally bacterial genes, but instead seem to originate from phages. When E. coli gets infected with a Shiga toxin-producing phage, it becomes a human pathogen [1]. David Acheson, managing director for food safety at consulting firm Leavitt Partners, says that exposure to antibiotics might be enhancing the spread of Shiga toxin-producing phage. Some antibiotics triggers what is referred to as the SOS response, which induces the phage to start replicating. The replication of the phage causes the bacteria to burst, releasing the phages, and with them the toxin [1].

Second, there is apparently an ongoing outbreak of scarlet fever in Hong Kong. Kwok-Yung Yuen, microbiologist at the University of Hong Kong, has analyzed the draft sequence of the genome, and suggests that the bacteria acquired greater virulence and drug resistance by picking up one or more genes from bacteria in the human oral and urogenital tracts. He believes that the overuse of antibiotics is driving the emergence of drug resistance in these bacteria [2].

Now, both of these cases are just indications, but if they are true that would be an alarming development, where the use of antibiotics promotes the spread not only of resistance genes, impairing our ability to treat bacterial infections, but also the development of far more virulent and aggressive strains. Combining increasing untreatability with increasing aggressiveness seems to me like the ultimate weapon against our relatively high standards of treatment of common infections. Good thing hand hygiene still seems to help [3].

References

1. Phage on the rampage (http://www.nature.com/news/2011/110609/full/news.2011.360.html), Published online 9 June 2011, Nature, doi:10.1038/news.2011.360
2. Mutated Bacteria Drives Scarlet Fever Outbreak (http://news.sciencemag.org/scienceinsider/2011/06/mutated-bacteria-drives-scarlet.html?etoc&elq=cd94aa347dca45b3a82f144b8213e82b), Published online 27 June 2011.
3. Luby SP, Halder AK, Huda T, Unicomb L, Johnston RB (2011) The Effect of Handwashing at Recommended Times with Water Alone and With Soap on Child Diarrhea in Rural Bangladesh: An Observational Study. PLoS Med 8(6): e1001052. doi:10.1371/journal.pmed.1001052 (http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001052)