Microbiology, Metagenomics and Bioinformatics

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

Browsing Posts tagged Novel antibiotics

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 will give a short talk on our findings related to antibiotic resistance associated with pharmaceutical production facilities in India at a one-hour webinar arranged by Healthcare Without Harm, taking place on Thursday, November 3rd, 10.00 CET. The webinar will discuss “hot-spot” environments in which antimicrobial resistance can emerge, such as areas in which there are poor pharmaceutical manufacturing practices, where expired or unused drugs are disposed of in an inappropriate way (i.e. by flushing them down the toilet or sink, or disposing them in household rubbish), and areas in which pharmaceuticals are used for aquaculture or agriculture. This is an important aspect of the resistance problem, but to date most of the actions taken to tackle the spread of AMR don’t take into account this aspect of antimicrobials released into the environment. The webinar is co-organised by HCWH Europe and HCWH Asia, and aims to raise awareness about the issue of AMR and its environmental impact. It features, apart from myself, Lucas Wiarda (Global Marketing Director & Head of Sustainable Antibiotics Program at DSM Sinochem Pharmaceuticals) and Sister Mercilyn Jabel (Pharmacist at Saint Paul Hospital Cavite, Philippines).

Sign up here to learn about:

  • Antibiotic pollution and waste
  • Recent findings from India regarding antibiotic discharges in rivers from manufacturers and new mechanisms by which resistance spreads in the environment
  • Sustainable antibiotics – how to support the proper and effective use of antibiotics and their responsible production
  • How the pharmaceutical industry is addressing the environmental pollution that leads to AMR
  • The best practices in managing infectious waste at hospital level

In a recent paper in Nature, a completely new antibiotic – teixobactin – is described (1). The really cool thing about this antibiotic is that it was discovered in a screen of uncultured bacteria, grown using new technology that enable controlled growth of single colonies in situ. I really like this idea, and I think the prospect of a novel antibiotic using a previously unexploited mechanism is super-promising, particularly in the light of alarming resistance development in clinically important pathogens (2,3). What really annoys me about the paper is the claim (already in the abstract) that since “we did not obtain any mutants of Staphylococcus aureus or Mycobacterium tuberculosis resistant to teixobactin (…) the properties of this compound suggest a path towards developing antibiotics that are likely to avoid development of resistance.” To me, this sounds pretty much like a bogus statement; in essence telling me that we apparently have not learned anything from the 70 years of antibiotics usage and resistance development. After working with antibiotic resistance a couple of years, particularly from the environmental perspective, I have a very disturbing feeling that there is already resistance mechanisms against teixobactin waiting out in the wild (4,5). Pretending that lack of mutation-associated resistance development means that there could not be resistance development did not help vancomycin (6,7), and we now see VRE (Vancomycin Resistant Enterococcus) showing up as a major problem in clinics. The “avoid development of resistance” claim is downright irresponsible, and the cynic in me cannot help to think that NovoBiotic Pharmaceuticals (the affiliation of almost half of the authors) has a monetary finger in this jar. In the end, time will tell how “resistance-resilient” teixobactin is and how well we can handle the gift of a novel antibiotic.

  1. Ling LL, Schneider T, Peoples AJ, Spoering AL, Engels I, Conlon BP, Mueller A, Schäberle TF, Hughes DE, Epstein S, Jones M, Lazarides L, Steadman VA, Cohen DR, Felix CR, Fetterman KA, Millett WP, Nitti AG, Zullo AM, Chen C, Lewis K: A new antibiotic kills pathogens without detectable resistance. Nature (2015). doi:10.1038/nature14098
  2. 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, 57: 704–710 (2013).
  3. French GL: The continuing crisis in antibiotic resistance. Int J Antimicrob Agents, 36 Suppl 3:S3–7 (2010).
  4. 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).
  5. Larsson DGJ: Antibiotics in the environment. Ups J Med Sci, 119: 108–112 (2014).
  6. Wright GD: Mechanisms of resistance to antibiotics. Curr Opin Chem Biol, 7:563–569 (2003).
  7. Werner G, Strommenger B, Witte W: Acquired vancomycin resistance in clinically relevant pathogens. Future Microbiol, 3: 547–562 (2008).