Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Jan 22:4:4.
doi: 10.3389/fmicb.2013.00004. eCollection 2013.

Evolutionary consequences of antibiotic use for the resistome, mobilome and microbial pangenome

Michael R Gillings  1
Affiliations

Evolutionary consequences of antibiotic use for the resistome, mobilome and microbial pangenome

Michael R Gillings. Front Microbiol. .

Abstract

The widespread use and abuse of antibiotic therapy has evolutionary and ecological consequences, some of which are only just beginning to be examined. One well known consequence is the fixation of mutations and lateral gene transfer (LGT) events that confer antibiotic resistance. Sequential selection events, driven by different classes of antibiotics, have resulted in the assembly of diverse resistance determinants and mobile DNAs into novel genetic elements of ever-growing complexity and flexibility. These novel plasmids, integrons, and genomic islands have now become fixed at high frequency in diverse cell lineages by human antibiotic use. Consequently they can be regarded as xenogenetic pollutants, analogous to xenobiotic compounds, but with the critical distinction that they replicate rather than degrade when released to pollute natural environments. Antibiotics themselves must also be regarded as pollutants, since human production overwhelms natural synthesis, and a major proportion of ingested antibiotic is excreted unchanged into waste streams. Such antibiotic pollutants have non-target effects, raising the general rates of mutation, recombination, and LGT in all the microbiome, and simultaneously providing the selective force to fix such changes. This has the consequence of recruiting more genes into the resistome and mobilome, and of increasing the overlap between these two components of microbial genomes. Thus the human use and environmental release of antibiotics is having second order effects on the microbial world, because these small molecules act as drivers of bacterial evolution. Continued pollution with both xenogenetic elements and the selective agents that fix such elements in populations has potentially adverse consequences for human welfare.

Keywords: evolvability; metagenomics; mobilome; pangenome; parvome; pollution; resistome.

PubMed Disclaimer

Figures

FIGURE 1
FIGURE 1
Conceptual schematic illustrating the production, export, and target sites of a small molecule biosynthetic cluster. The metabolic pathway for synthesis of a small molecule is encoded by genes A, B, and C. One of the intermediates (triangle) is exported from the cell via an efflux pump, where it can then bind to cell surface receptors, or enter a second cell via a membrane transport protein. Inside the second cell there may be binding sites on additional target molecules. Most of the molecules we know as antibiotics may be a subset of this more general class of signal-receptor systems.
FIGURE 2
FIGURE 2
Conceptual representation of the biological molecules of relevance to antibiotic resistance. The small cross-hatched boxes represent the antibiotics and resistance genes of relevance to clinical practice. Respectively, these are a small subset of the world of small bioactive molecules (the parvome), and the world of potential resistance determinants (the resistome). The resistome comprises the genes that potentially encode resistance to antibiotics. The mobilome comprises the mobile proportion of bacterial genomes. The mobilome and resistome overlap, since many resistance genes are located on mobile elements. Both the resistome and mobilome are a subset of the total coding capacity of prokaryotic cells, the pangenome, which is expressed as the panproteome. Note that only a small proportion of the parvome is utilized by humans for antibiotic purposes, and that the scale of commercial antibiotic production probably overwhelms the natural production of these molecules by the entire global microbiota.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Aertsen A., Michiels C. W. (2006). Upstream of the SOS response: figure out the trigger. Trends Microbiol. 14 421–423 - PubMed
    1. Allen H. K., Donato J., Wang H. H., Cloud-Hansen K. A., Davies J., Handelsman J. (2010). Call of the wild: antibiotic resistance genes in natural environments. Nat. Rev. Microbiol. 8 251–259 - PubMed
    1. Allen H. K., Moe L. A., Rodbumrer J., Gaarder A., Handelsman J. (2008). Functional metagenomics reveals diverse β-lactamases in a remote Alaskan soil. ISME J. 3 243–251 - PubMed
    1. Aminov R. I., Mackie R. I. (2007). Evolution and ecology of antibiotic resistance genes. FEMS Microbiol. Lett. 271 147–161 - PubMed
    1. Baker-Austin C., Wright M. S., Stepanauskas R., McArthur J. V. (2006). Co-selection of antibiotic and metal resistance. Trends Microbiol. 14 176–182 - PubMed

LinkOut - more resources