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UK OFFICE : +44 (0)1260 273 802
BRUSSELS OFFICE : +32 (0)2 895 5909

Special Reports
Fig. 1: Interaction between microbial communities from different environments affects the mobilome composition and antibiotic resistance gene reservoir

A better understanding of antibiotic resistance

16/12/15

Antibiotic-resistant bacteria already existed in the environment before antibiotics were used in human medicine. 1 Antibiotic resistance-conferring genes are usually located on mobile genetic elements (MGEs). Besides promoting the development of new resistance traits, the way and extent we use antibiotics today also selects for existing resistant clones within microbial populations and promotes their expansion. The spread of antibiotic resistance genes and the development of multidrug resistance represent major threats to public health. 2

As antibiotics are not only used in human and veterinary medicine, but also in animal food production and agriculture,3, 4 the environment plays an important role in the spread of antibiotic resistances, because it provides a multitude of relevant niches (soil, water, plants, animals) for the spread of resistance. Already in 2001, the European Council Recommendation on the prudent use of antimicrobial agents in human medicine underlined the idea that the occurrence of antibiotic resistance in human pathogens correlates with their occurrence in animals and the environment.5 Against this background, also the European Food Safety Authority (EFSA) has re-evaluated antibacterial products used as feed additives and their impact on resistance development to antibiotics of human and veterinary importance.6 Based on a recent decision of the European Commission regarding the monitoring of antimicrobial resistance in zoonotic and commensal agents in food-producing animals and meat, the detection of changes in antibiotic resistance patterns in animal populations should help to define future trends in the occurrence of antimicrobial resistance.7

So far, microbial pathogens and individual MGEs carrying resistance determinants have been intensively studied regarding the spread of antimicrobial drug resistance. The composition and dynamics of the general bacterial mobile gene pool in a given niche or environment, the so-called ‘mobilome’, has not been comprehensively studied so far. The mobilome consists of MGEs, including plasmids, bacteriophages, genomic islands (GEIs), integrative and conjugative elements (ICEs), integrons and transposons. These MGEs can frequently carry antibiotic resistance genes and serve as vectors for the lateral dissemination of antibiotic resistance determinants between microbes. Among MGEs, plasmids, which can carry (multiple) resistance determinants, are among the most important vehicles for the spread of antibiotic resistance. In order to better understand the constraints and driving forces of lateral gene transfer (LTG), we have to determine the molecular basis of the bacterial host range of resistance plasmids, the contribution of environmental conditions to the transfer efficiency of such plasmids and the impact that resistance plasmid carriage has on the fitness and competitiveness of the recipient hosts.

The uptake and exchange of bacteria between the environment, animals and humans increases the diversity and dynamics of the mobilome. In the wake of metagenomic analyses, also the prevalence of antibiotic resistance genes in the commensal microbiota is more and more in the research focus. Recent analyses indicate that resistance genes are widely distributed in the intestinal gut microbiota of healthy individuals.8,9,10 It has also been shown that the rate of LGT in the gut microbiota is remarkably high, sometimes being much higher than in other environments.11,12,13 Accordingly, the detailed analysis of the intestinal mobilome, not only in humans, but also in companion and food animals is critical for our understanding of the spread of antibiotic resistance as well as for relevant preventive approaches.10,14 Although we are slowly beginning to elucidate the relevance of certain compositional changes of the microbiota regarding its impact on human health, our knowledge of the mobilome in general, the interplay between different mobilome components, and their transmission and persistence including resistance genes, is still limited.

In summary, there is an urgent need to apply new comprehensive ‘omics’ approaches to increase our knowledge of the diversity, dynamics and evolution of antibiotic resistance genes including their vectors. We should intensify the analysis of the interplay and exchange of MGEs in complex microbial consortia in relevant reservoirs and environmental niches, including populations of wild and domesticated animals as well as humans.

ukmlogo wwulogo

Professor Dr Ulrich Dobrindt
Institute of Hygiene
University of Münster
Mendelstr. 7
48149 Münster
Germany
+49 (0)251 980-2875
dobrindt@uni-muenster.de
http://campus.uni-muenster.de/index.php?id=5401&L=1

1 D’Costa VM, King CE, Kalan L, Morar M, Sung WWL, Schwarz C, Froese D, Zazula G, Calmels F, Debruyne R, Golding GB, Poinar HN, Wright GD. (2011) Antibiotic resistance is ancient. Nature 477:457–461.

2 McKenna M (2013) Antibiotic resistance: the last resort. Nature 499:394–396, 10.1038/499394a.

3 Marshall BM, Levy SB (2011) Food animals and antimicrobials: impacts on human health. Clin Microbiol Rev. 24:718-733.

4 Garcia-Alvarez L, Dawson S, Cookson B, Hawkey P. (2012) Working across the veterinary and human health sectors. J Antimicrob  Chemother. 67:i37-49.

5 European Council (2001) Council Recommendation of 15.11.2001 on the Prudent Use of Antimicrobial Agents in Human Medicine (2002/77/EC). OJ L34 of 5.2.2002, p.13 European Council (EC), Brussels, Belgium.

6 The European Food Safety Authority (EFSA) Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) (2012) Guidance on the assessment of bacterial susceptibility to antimicrobials of human and veterinary importance. EFSA J, 10:2740

7 European Commission (2013) Commission Implementing Decision 613/2013 of 12.11.2013 on the monitoring and reporting of antimicrobial resistance in zoonotic and comensal bacteria.

8 Hu Y, Yang X, Qin J, Lu N, Cheng G, Wu N, Pan Y, Li J, Zhu L, Wang X, Meng Z, Zhao F, Liu D, Ma J, Qin N, Xiang C, Xiao Y, Li L, Yang H, Wang J, Yang R, Gao GF, Wang J, Zhu B (2013) Metagenome-wide analysis of antibiotic resistance genes in a large cohort of human gut microbiota. Nat Commun. 4:2151.

9 Sommer MOA, Dantas G, Church GM (2009) Functional Characterization of the Antibiotic Resistance Reservoir in the Human Microflora. Science 325:1128–1131.

10 Smillie CS1, Smith MB, Friedman J, Cordero OX, David LA, Alm EJ (2011) Ecology drives a global network of gene exchange connecting the human microbiome. Nature 480:241-244.

11 Stecher B, Denzler R, Maier L, Bernet F, Sanders MJ, Pickard DJ, Barthel M, Westendorf AM, Krogfelt KA, Walker AW, Ackermann M, Dobrindt U, Thomson NR, Hardt WD (2012) Gut inflammation can boost horizontal gene transfer between pathogenic and commensal Enterobacteriaceae. Proc Natl Acad Sci USA 109(4):1269-1274.

12 Modi SR, Lee HH, Spina CS, Collins JJ (2013) Antibiotic treatment expands the resistance reservoir and ecological network of the phage metagenome. Nature 499:219–222.

13 Devirgiliis C, Barile S, Perozzi G (2011) Antibiotic resistance determinants in the interplay between food and gut microbiota. Genes Nutr. 6:275–284.

14 Sekirov I, Russell SL, Antunes LC, Finlay BB (2010) Gut microbiota in health and disease. Physiol Rev. 90:859-904.

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Professor Dr Ulrich Dobrindt
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Institute of Hygiene, University of Münster
Telephone
+49 (0)251 980-2875
Institute of Hygiene, University of Münster
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