Antimicrobial Resistance: Adapt or perish

Microbial communities in wastewater treatment plants provide insights into the development and mechanisms of antimicrobial resistance.
  1. Rohan BH Williams  Is a corresponding author
  1. Singapore Centre for Environmental Life Sciences Engineering, National University of Singapore, Singapore

Bacteria and other microbes are probably the most successful life forms on Earth. They are ubiquitous and can survive in a large range of habitats, from extreme environments to the human body. One of the reasons for their success is their potential to adapt to changing conditions, including drug treatments.

Antimicrobial resistance – the ability of bacteria to evolve resistance to drug treatments, including antibiotics – poses a major threat to health interventions (McEwen and Collignon, 2018). Although antimicrobial resistance occurs naturally, the widespread and often uncontrolled use of antibiotics in both humans and livestock have exacerbated this ability. As a consequence, treatment of many common bacterial infections, such as sepsis, or urinary and sexually transmitted infections, is now compromised.

Bacteria acquire antimicrobial resistance in two main ways: one is through favourable mutations in the DNA during cell replication; the other is by exchanging genetic material that often contain genes mediating antimicrobial resistance, also known as horizontal gene transfer (Haudiquet et al., 2022). While the mechanisms of genetic transfers – and how they contribute to antibiotics resistance – have been understood for decades, it has been less clear how they work in the ‘real world’. Now, in eLife, Paul Wilmes and colleagues at the University of Luxembourg – including Laura de Nies as first author – report new insights about antimicrobial resistance using wastewater treatment plants as an example (de Nies et al., 2022).

While microbial communities in wastewater thrive on the nutrient-rich streams from sewage systems, they also encounter a range of micropollutants arising from human domestic and industrial activity, including antibiotics. Bacteria – including the ones carrying antimicrobial resistance genes – also enter the wastewater system. These conditions provide ample opportunities for the evolution and/or transmission of antimicrobial resistance. Subsequently, the risk of such resistant bacteria being transmitted into natural water systems and eventually back into human or animal populations, is extremely high (Pruden et al., 2021).

The researchers analysed previously collected multi-omics datasets that contained sequences of all the DNA found in a wastewater treatment plant. This allowed them to identify both the genomes of species within the community and the mobile genetic elements that can be transferred between bacteria. Using metatranscriptomics and metaproteomics, two techniques that measure which genes are active (McDaniel et al., 2021), de Nies et al. were able to further analyse gene expression at the level of the entire microbial community. Samples were collected over one and a half years, which allowed the researchers to assess the dynamic changes in the inter-relationship between microbes and mobile genetic elements.

In total, de Nies et al. identified 29 different major types of antimicrobial resistance genes. The relative abundance of these types changed slightly over time, which could be linked to changes in resistant entities within the community, either due to the transfer of such genes, to changes in the composition of bacteria, or both. Overall, antimicrobial genes that provide protection against multiple drugs, and those that provide resistance against two common types of antibiotics (aminoglycosides and beta lactams) were both abundant and highly expressed.

Interestingly, the most highly expressed genes were related to resistance against antimicrobial peptides, which are part of the innate immune system in multicellular organisms. One of these was a gene called YojI, which encodes resistance to microcin, a common toxin that is widely produced by bacteria and other prokaryotic species. It was found in about 90% of all expressed transcripts attributed to this type of antimicrobial resistance, suggesting that many species in the community produce microcin as a survival strategy, and thus also require resistance to toxins produced by other species.

To better understand the mechanisms underlying antimicrobial resistance within microbial communities in wastewater, de Nies et al. next focused on two relevant types of mobile genetic elements that convey antimicrobial resistance genes: plasmids (small, circular DNA molecules) and bacteriophages (viruses that infect bacteria). The analyses confirmed that the majority of antimicrobial resistance genes are harboured in bacterial chromosomal DNA, but plasmids and phages nevertheless transmitted 11% and 7% of those genes, respectively.

There appears to be a preferential link between the types of resistance genes and the types of mobile genetic element that carry them. Further analyses indicated that several human pathogenic bacteria only express antimicrobial resistance genes associated with plasmids, which suggests that these genes may be more easily and widely transmitted. The study by de Nies et al. also documents a wide variety of resistance genes in a key set of human pathogens, known as the ESKAPEE species, that are also present in the microbial community of the wastewater treatment plant.

The work of de Nies et al. highlights how variable the transmission of resistance pathways within complex environments can be. More targeted observational studies may be warranted to fully understand the transmission flows of these genetic materials. For example, the new metagenomic assays that can infer the colocalization of DNA from chromosomes and mobile genetic elements (within the same microbial cell) would paint a more accurate picture (Stalder et al., 2019); but these techniques are also much more complex compared to bulk DNA sequencing.

Wastewater treatment plants play a critical role in both mitigating the impact of human waste on natural water sources and preventing ‘feed-backs’ of pathogens into human populations. They are also important surveillance systems that can monitor the spread of viruses that people shed in their faeces. Understanding the various pathways of resistance transmission – including the role of plasmids and phages – will help to understand the ecological relationships between human, animals and the natural environment. In the future, wastewater plants could be used to monitor antimicrobial resistance and their potential threat to human health, and to guide initiatives that prevent the release of such resistant bacteria back into the environment (Pruden et al., 2021).

References

Article and author information

Author details

  1. Rohan BH Williams

    Rohan BH Williams is in the Singapore Centre for Environmental Life Sciences Engineering, National University of Singapore, Singapore, Singapore

    For correspondence
    LSIRBHW@nus.edu.sg
    Competing interests
    No competing interests declared
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1286-5277

Publication history

  1. Version of Record published:

Copyright

© 2022, Williams

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 552
    views
  • 67
    downloads
  • 1
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Rohan BH Williams
(2022)
Antimicrobial Resistance: Adapt or perish
eLife 11:e83617.
https://doi.org/10.7554/eLife.83617
  1. Further reading

Further reading

    1. Microbiology and Infectious Disease
    Tao Tang, Weiming Zhong ... Zhipeng Gao
    Research Article

    Saprolegnia parasitica is one of the most virulent oomycete species in freshwater aquatic environments, causing severe saprolegniasis and leading to significant economic losses in the aquaculture industry. Thus far, the prevention and control of saprolegniasis face a shortage of medications. Linalool, a natural antibiotic alternative found in various essential oils, exhibits promising antimicrobial activity against a wide range of pathogens. In this study, the specific role of linalool in protecting S. parasitica infection at both in vitro and in vivo levels was investigated. Linalool showed multifaceted anti-oomycetes potential by both of antimicrobial efficacy and immunomodulatory efficacy. For in vitro test, linalool exhibited strong anti-oomycetes activity and mode of action included: (1) Linalool disrupted the cell membrane of the mycelium, causing the intracellular components leak out; (2) Linalool prohibited ribosome function, thereby inhibiting protein synthesis and ultimately affecting mycelium growth. Surprisingly, meanwhile we found the potential immune protective mechanism of linalool in the in vivo test: (1) Linalool enhanced the complement and coagulation system which in turn activated host immune defense and lysate S. parasitica cells; (2) Linalool promoted wound healing, tissue repair, and phagocytosis to cope with S. parasitica infection; (3) Linalool positively modulated the immune response by increasing the abundance of beneficial Actinobacteriota; (4) Linalool stimulated the production of inflammatory cytokines and chemokines to lyse S. parasitica cells. In all, our findings showed that linalool possessed multifaceted anti-oomycetes potential which would be a promising natural antibiotic alternative to cope with S. parasitica infection in the aquaculture industry.

    1. Genetics and Genomics
    2. Microbiology and Infectious Disease
    Iti Mehta, Jacob B Hogins ... Larry Reitzer
    Research Article

    Polyamines are biologically ubiquitous cations that bind to nucleic acids, ribosomes, and phospholipids and, thereby, modulate numerous processes, including surface motility in Escherichia coli. We characterized the metabolic pathways that contribute to polyamine-dependent control of surface motility in the commonly used strain W3110 and the transcriptome of a mutant lacking a putrescine synthetic pathway that was required for surface motility. Genetic analysis showed that surface motility required type 1 pili, the simultaneous presence of two independent putrescine anabolic pathways, and modulation by putrescine transport and catabolism. An immunological assay for FimA—the major pili subunit, reverse transcription quantitative PCR of fimA, and transmission electron microscopy confirmed that pili synthesis required putrescine. Comparative RNAseq analysis of a wild type and ΔspeB mutant which exhibits impaired pili synthesis showed that the latter had fewer transcripts for pili structural genes and for fimB which codes for the phase variation recombinase that orients the fim operon promoter in the ON phase, although loss of speB did not affect the promoter orientation. Results from the RNAseq analysis also suggested (a) changes in transcripts for several transcription factor genes that affect fim operon expression, (b) compensatory mechanisms for low putrescine which implies a putrescine homeostatic network, and (c) decreased transcripts of genes for oxidative energy metabolism and iron transport which a previous genetic analysis suggests may be sufficient to account for the pili defect in putrescine synthesis mutants. We conclude that pili synthesis requires putrescine and putrescine concentration is controlled by a complex homeostatic network that includes the genes of oxidative energy metabolism.