Frank M Aarestrup

National Food and Nutrition Institute, Warszawa, Masovian Voivodeship, Poland

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Publications (293)1027.95 Total impact

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    ABSTRACT: Methicillin-resistant Staphylococcus aureus (MRSA) Sequence Type (ST)1, Clonal Com-plex(CC)1, SCCmec V is one of the major Livestock-Associated (LA-) lineages in pig farming industry in Italy and is associated with pigs in other European countries. Recently, it has been increasingly detected in Italian dairy cattle herds. The aim of this study was to analyse the differences between ST1 MRSA and methicillin-susceptible S. aureus (MSSA) from cattle and pig herds in Italy and Europe and human isolates. Sixty-tree animal isolates from different holdings and 20 human isolates were characterized by pulsed-field gel electrophoresis (PFGE), spa-typing, SCCmec typing, and by micro-array analysis for several virulence, antimicrobial resistance, and strain/host-specific marker genes. Three major PFGE clusters were detected. The bovine isolates shared a high (90% to 100%) similarity with human isolates and carried the same SCCmec type IVa. They often showed genetic features typical of human adaptation or present in human-associated CC1: Immune evasion cluster (IEC) genes sak and scn, or sea; sat and aphA3-mediated aminoglycoside resistance. Contrary, typical markers of porcine origin in Italy and Spain, like erm(A) mediated macrolide-lincosamide-streptograminB, and of vga(A)-mediated pleuromutilin resistancewere always absent in human and bovine isolates. Most of ST(CC)1 MRSA from dairy cattle were multidrug-resistant and contained virulence and immunomodulatory genes associated with full capability of colonizing humans. As such, these strains may represent a greater human hazard than the porcine strains. The zoonotic capacity of CC1 LA-MRSA from livestock must be taken seriously and measures should be implemented at farm-level to prevent spill-over.
    PLoS ONE 08/2015; 10(8). DOI:10.1371/journal.pone.0137143 · 3.23 Impact Factor
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    ABSTRACT: Human populations worldwide are increasingly confronted with infectious diseases and antimicrobial resistance spreading faster and appearing more frequently. Knowledge regarding their occurrence and worldwide transmission is important to control outbreaks and prevent epidemics. Here, we performed shotgun sequencing of toilet waste from 18 international airplanes arriving in Copenhagen, Denmark, from nine cities in three world regions. An average of 18.6 Gb (14.8 to 25.7 Gb) of raw Illumina paired end sequence data was generated, cleaned, trimmed and mapped against reference sequence databases for bacteria and antimicrobial resistance genes. An average of 106,839 (0.06%) reads were assigned to resistance genes with genes encoding resistance to tetracycline, macrolide and beta-lactam resistance genes as the most abundant in all samples. We found significantly higher abundance and diversity of genes encoding antimicrobial resistance, including critical important resistance (e.g. blaCTX-M) carried on airplanes from South Asia compared to North America. Presence of Salmonella enterica and norovirus were also detected in higher amounts from South Asia, whereas Clostridium difficile was most abundant in samples from North America. Our study provides a first step towards a potential novel strategy for global surveillance enabling simultaneous detection of multiple human health threatening genetic elements, infectious agents and resistance genes.
    Scientific Reports 07/2015; 5:11444. DOI:10.1038/srep11444 · 5.58 Impact Factor
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    ABSTRACT: Six strains of Enterococcus faecalis (S1, S12, S17, S18, S19 and S32) were isolated from copper fed pigs in Denmark. These Gram-positive bacteria within the genus Enterococcus are able to survive a variety of physical and chemical challenges by the acquisition of diverse genetic elements. The genome of strains S1, S12, S17, S18, S19 and S32 contained 2,615, 2,769, 2,625, 2,804, 2,853 and 2,935 protein-coding genes, with 41, 42, 27, 42, 32 and 44 genes encoding antibiotic and metal resistance, respectively. Differences between Cu resistant and sensitive E. faecalis strains, and possible co-transfer of Cu and antibiotic resistance determinants were detected through comparative genome analysis.
    Standards in Genomic Sciences 07/2015; 10(35). DOI:10.1186/s40793-015-0021-1 · 3.17 Impact Factor
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    ABSTRACT: Probiotics are increasingly used in aquaculture to control diseases and improve feed digestion and pond water quality; however, little is known about the antimicrobial resistance properties of such probiotic bacteria and to what extent they may contribute to the development of bacterial resistance in aquaculture ponds. Concerns have been raised that the declared information on probiotic product labels are incorrect and information on bacterial composition are often missing. We therefore evaluated seven probiotics commonly used in Vietnamese shrimp culture for their bacterial species content, phenotypic antimicrobial resistance and associated transferable resistance genes. The bacterial species was established by 16S rRNA sequence analysis of 125 representative bacterial isolates. MIC testing was done for a range of antimicrobials and whole genome sequencing of six multiple antimicrobial resistant Bacillus spp. used to identify resistance genes and genetic elements associated with horizontal gene transfer. Thirteen bacterial species declared on the probiotic products could not be identified and 11 non-declared Bacillus spp. were identified. Although our culture-based isolation and identification may have missed a few bacterial species present in the tested products this would represent minor bias, but future studies may apply culture independent identification methods like pyro sequencing. Only 6/60 isolates were resistant to more than four antimicrobials and whole genome sequencing showed that they contained macrolide (ermD), tetracycline (tetL), phenicol (fexA) and trimethoprim (dfrD, dfrG and dfrK) resistance genes, but not known structures associated with horizontal gene transfer. Probiotic bacterial strains used in Vietnamese shrimp culture seem to contribute with very limited types and numbers of resistance genes compared to the naturally occurring bacterial species in aquaculture environments. Approval procedures of probiotic products must be strengthened through scientific-based efficacy trials and product labels should allow identification of individual bacterial strains and inform the farmer on specific purpose, dosage and correct application measures.
    PLoS ONE 07/2015; 10(7):e0132338. DOI:10.1371/journal.pone.0132338 · 3.23 Impact Factor
  • Frank M Aarestrup
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    ABSTRACT: The purpose of this review was to provide an updated overview on the use of antimicrobial agents in livestock, the associated problems for humans and current knowledge on the effects of reducing resistance in the livestock reservoir on both human health and animal production. There is still limiting data on both use of antimicrobial agents, occurrence and spread of resistance as well as impact on human health. However, in recent years, emerging issues related to methicillin-resistant Staphylococcus aureus, Clostridium difficile, Escherichia coli and horizontally transferred genes indicates that the livestock reservoir has a more significant impact on human health than was estimated 10 years ago, where the focus was mainly on resistance in Campylobacter and Salmonella. Studies have indicated that there might only be a marginal if any benefit from the regular use of antibiotics and have shown that it is possible to substantially reduce the use of antimicrobial agents in livestock production without compromising animal welfare or health or production. In some cases, this should be done in combination with other measures such as biosecurity and use of vaccines. To enable better studies on both the global burden and the effect of interventions, there is a need for global harmonized integrated and continuous surveillance of antimicrobial usage and antimicrobial resistance, preferably associated with data on production and animal diseases to determine the positive and negative impact of reducing antimicrobial use in livestock. © 2015 The Author(s) Published by the Royal Society. All rights reserved.
    Philosophical Transactions of The Royal Society B Biological Sciences 06/2015; 370(1670). DOI:10.1098/rstb.2014.0085 · 7.06 Impact Factor
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    ABSTRACT: Accurate and rapid typing of pathogens is essential for effective surveillance and outbreak detection. Conventional serotyping of Escherichia coli is a delicate, laborious, time-consuming and expensive procedure. With whole-genome sequencing (WGS) becoming cheaper, it has vast potential in routine typing and surveillance. The aim of this study was to establish a valid and publicly available tool for WGS-based in silico serotyping of E. coli applicable for routine typing and surveillance. A FASTA database of specific O-antigen processing system genes for O-typing and flagellin genes for H-typing was created as a component of the publicly available web-tools hosted by the Center for Genomic Epidemiology (CGE) ( All E. coli isolates available with WGS data and conventional serotype information were subjected to WGS-based serotyping employing this specific SerotypeFinder CGE-tool. The SerotypeFinder was evaluated on 682 E. coli genomes, 108 of which were sequenced for this study, where both the whole genome and the serotype were available. In total, 601 and 509 isolates were included for O -and H-typing, respectively. O-antigen genes wzx, wzy, wzm and wzt, and flagellin genes fliC, flkA, fllA, flmA and flnA were detected in 569 and 508 genome sequences respectively. The SerotypeFinder for WGS-based O -and H-typing predicted 560 of 569 O types and 504 of 508 H types consistent with conventional serotyping. In combination with other available WGS-typing tools, E. coli serotyping can be performed solely from WGS-data, providing faster and cheaper typing than current routine procedures, making WGS-typing a superior alternative to conventional typing strategies. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Journal of clinical microbiology 05/2015; 53(8):2410-2426. DOI:10.1128/JCM.00008-15 · 3.99 Impact Factor
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    ABSTRACT: The genome of a multidrug-resistant Salmonella Agona isolated from Larus audouinii (Audouin's gull) in Spain was examined. The isolate showed high levels of resistance to different antimicrobials, including third generation cephalosporins and fluoroquinolones, which is a public health concern as those being used to treat severe salmonellosis in humans. Whole genome sequencing revealed the strain being multilocus sequence type ST13, and eight resistance genes (aadA2, aadB, blaCTX-M-9,blaDHA-1, qnrA1, tetA, sul1 and dfrA16) belonging to seven antimicrobial classes were confirmed, as well as the presence of two plasmids. Migratory Audouin's gulls have the ability to cover long distances during annual movements. Therefore, they have the potential to disseminate multidrug-resistant Salmonella and resistance genes in the environment and over great geographic distances, contributing to the global dissemination of resistance genes. © FEMS 2014. All rights reserved. For permissions, please e-mail:
    FEMS Microbiology Letters 02/2015; 362(3):1-4. DOI:10.1093/femsle/fnu039 · 2.12 Impact Factor
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    ABSTRACT: Salmonella enterica serovar Choleraesuis is a porcine adapted serovar which may cause serious outbreaks in pigs. Here we describe outbreaks of salmonellosis due to S. Choleraesuis in four Danish pig farms in 2012-2013 by clinic, serology, and microbiology and compare the isolates to those of a previous outbreak in 1999-2000. The infection was in some herds associated with high mortality and a moderate to high sero-prevalence was found. In 2012-2013 the disease contributed to increased mortality but occurred concomitant with other disease problems in the herds, which likely delayed the diagnosis by up to several months. Nine isolates from the four farms in 2012-2013 and 14 isolates obtained from the outbreak in Denmark in 1999-2000 were subjected to typing using pulsed-field gel electrophoresis (PFGE). Seven isolates were selected for whole genome sequencing (WGS). The PFGE results of 23 isolates displayed five different profiles. The isolates from 2012 to 2013 revealed two distinct profiles, both different from the isolates recovered in 1999-2000. Two of the 2012-2013 farms shared PFGE profiles and had also transported pigs between them. The profile found in the two other 2012-2013 farms was indistinguishable but no epidemiological connection between these farms was found. Analysis of the number of single nucleotide polymorphisms (SNPs) from the WGS data indicated that the isolates from the farms in 2012-2013 were more closely related to each other than to isolates from the outbreak in 1999. It was therefore concluded that the infection was a new introduction and not a persistent infection since the outbreak in 1999. It may further be suggested that there were two or three independent rather than a single introduction. The re-introduction of S. Choleraesuis in Denmark emphasizes the importance of strict hygiene measures in the herds. Further investigations using WGS are now in progress on a larger collection of isolates to study clonality at European level and trace the origin of the infections. Copyright © 2015 Elsevier B.V. All rights reserved.
    Veterinary Microbiology 01/2015; 176(3-4). DOI:10.1016/j.vetmic.2015.01.004 · 2.51 Impact Factor
  • Marie Bjødstrup Jensen · Helga Schumacher · Henrik Hasman · Frank Møller Aarestrup
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    ABSTRACT: Pasteurella multocida inhabits the upper respiratory tract of many animals. It can cause skin and soft tissue infections in humans, usually in association with animal bites. We present a case of a 66-year-old chemotherapy-induced immunocompromised patient with lung cancer, who was treated for pneumonia and septicaemia due to P. multocida. There was no anamnestic contact with animals, which underlines the fact that immunocompromised patients can suffer from serious systemic infections due to P. multocida - even with no known animal contact.
    Ugeskrift for laeger 12/2014; 176(25A).
  • Mikala Wang · Lars Borris · Frank Møller Aarestrup · Henrik Hasman
    International Journal of Antimicrobial Agents 12/2014; 45(3). DOI:10.1016/j.ijantimicag.2014.11.004 · 4.30 Impact Factor
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    ABSTRACT: One unreported case of ESBL-producing Typhi was identified, whole genome sequence typed among other analysis and compared to other available genomes of Typhi. The reported strain was similar to a previously published strain harbouring blaSHV-12 from the Philippines and likely part of an undetected outbreak; the first of ESBL-producing Typhi. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
    Journal of Clinical Microbiology 11/2014; 53(2). DOI:10.1128/JCM.03104-14 · 3.99 Impact Factor
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    ABSTRACT: Retrospectively, we investigated the epidemiology of a massive Salmonella enterica serovar Typhi outbreak in Zambia during 2010 to 2012. Ninety-four isolates were susceptibility tested by MIC determinations. Whole genome sequence typing (WGST) of 33 isolates and bioinformatic analysis identified the MLST, haplotype, plasmid replicon, antimicrobial resistance genes, and the genetic relatedness by Single Nucleotide Polymorphism (SNP) analysis and genomic deletions. The outbreak affected 2,040 patients with a fatality rate of 0.5%. Most isolates (83.0%) were multi-drug resistant (MDR). The isolates belonged to MLST ST1 and a new variant of the haplotype; H58B. Most isolates contained a chromosomally translocated region containing seven antimicrobial resistance genes; catA1, blaTEM-1, dfrA7, sul1, sul 2, strA, and strB, fragments of incQ1plasmid replicon, class 1 integron, and the mer operon. The genomic analysis revealed an overall 415 SNPs difference and 35 deletions among 33 of the isolates whole genome sequenced. In comparison with other genomes of H58, the Zambian isolates separated from genomes from Central Africa and India with 34 and 52 SNPs, respectively. The phylogenetic analysis indicates that 32 isolates of the 33 sequenced belonged to a tight clonal group, distinct from other H58 genomes included in the study. The small numbers of SNPs identified within this group are consistent with short-term transmission that can be expected over a period of 2 years. The phylogenetic analysis and deletions suggest that a single MDR clone was responsible for the outbreak during which occasional other S. Typhi lineages including sensitive ones continued to co-circulate. The common view is that the emerging global S. Typhi haplotype; H58B, containing the MDR incHI1 plasmid is responsible for the majority of typhoid infections in Asia and sub-Saharan Africa; we found that a new variant of the haplotype harbouring a chromosomally translocated region containing the MDR islands of incHI1 plasmid emerged in Zambia. This could chance the perception of the term "classical MDR typhoid" currently being solely associated with the incHI1 plasmid. It might be more common than anticipated that S. Typhi haplotype; H58B harbour either the incHI1 plasmid and /or a chromosomally translocated MDR region.
    Journal of Clinical Microbiology 11/2014; 53(1). DOI:10.1128/JCM.02026-14 · 3.99 Impact Factor
  • Louise Roer · Frank M Aarestrup · Henrik Hasman
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    ABSTRACT: The rapid evolution of bacteria is crucial to their survival and is caused by exchange, transfer, and uptake of DNA, among other things. Conjugation is one of the main mechanisms by which bacteria share their DNA, and it is thought to be controlled by varied bacterial immune systems. Contradictory results about restriction-modification systems based on phenotypic studies have been presented as reasons for a barrier to conjugation with and other means of uptake of exogenous DNA. In this study, we show that inactivation of the R.EcoKI restriction enzyme in strain Escherichia coli K-12 strain MG1655 increases the conjugational transfer of plasmid pOLA52, which carriers two EcoKI recognition sites. Interestingly, the results were not absolute, and uptake of unmethylated pOLA52 was still observed in the wild-type strain (with an intact hsdR gene) but at a reduction of 85% compared to the uptake of the mutant recipient with a disrupted hsdR gene. This leads to the conclusion that EcoKI restriction-modification affects the uptake of DNA by conjugation but is not a major barrier to plasmid transfer.
    Journal of Bacteriology 11/2014; 197(2). DOI:10.1128/JB.02418-14 · 2.81 Impact Factor
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    ABSTRACT: The draft genome sequences of two copper-resistant Escherichia coli strains were determined. These had been isolated from copper-fed pigs and contained additional putative operons conferring copper and other metal and metalloid resistances.
    Genome Announcements 11/2014; 2(6). DOI:10.1128/genomeA.01341-14
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    ABSTRACT: Salmonella typhimurium is the causative agent of typhoid fever, which causes nearly 21.7 million illnesses and 217,000 deaths around the world each year. Here, we describe the draft genome sequences of the Salmonella typhimurium strains S7, S15, and S23, isolated from copper-fed pigs in Denmark and containing additional putative determinants conferring resistances to copper and other metals and metalloids.
    Genome Announcements 11/2014; 2(6). DOI:10.1128/genomeA.01334-14
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    Rolf S Kaas · Pimlapas Leekitcharoenphon · Frank M Aarestrup · Ole Lund
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    ABSTRACT: Whole genome sequencing (WGS) shows great potential for real-time monitoring and identification of infectious disease outbreaks. However, rapid and reliable comparison of data generated in multiple laboratories and using multiple technologies is essential. So far studies have focused on using one technology because each technology has a systematic bias making integration of data generated from different platforms difficult. We developed two different procedures for identifying variable sites and inferring phylogenies in WGS data across multiple platforms. The methods were evaluated on three bacterial data sets and sequenced on three different platforms (Illumina, 454, Ion Torrent). We show that the methods are able to overcome the systematic biases caused by the sequencers and infer the expected phylogenies. It is concluded that the cause of the success of these new procedures is due to a validation of all informative sites that are included in the analysis. The procedures are available as web tools.
    PLoS ONE 08/2014; 9(8):e104984. DOI:10.1371/journal.pone.0104984 · 3.23 Impact Factor
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    ABSTRACT: Objectives: To compare and characterize extended-spectrum β-lactamase (ESBL)-producing Escherichia coli from pigsties, pig farmers and their families on farms with previous high or no use of third- or fourth-generation cephalosporins. Methods: Twenty farms with no third- or fourth-generation cephalosporin use and 19 herds with previous frequent use were included. The ESBL-producing isolates detected in humans and pigs were characterized by ESBL genotype, PFGE, susceptibility to non-β-lactam antibiotics and phylotype, and selected isolates were characterized by multilocus sequence typing (MLST). Furthermore, transferability of bla(CTX-M-)1 from both human and pig isolates was studied and plasmid incompatibility groups were defined. The volunteers answered a questionnaire including epidemiological risk factors for carriage of ESBL-producing E. coli. Results: ESBL-producing E. coli was detected in pigs on 79% of the farms with high consumption of cephalosporins compared with 20% of the pigs on farms with no consumption. ESBL-producing E. coli was detected in 19 of the 195 human participants and all but one had contact with pigs. The genes found in both humans and pigs at the same farms were blaCTX-M-1 (eight farms), bla(CTX-M-14) (one farm) and bla(SHV-12) (one farm). At four farms ESBL-producing E. coli isolates with the same CTX-M enzyme, phylotype, PFGE type and MLST type were detected in both pigs and farmers. The majority of the plasmids with bla(CTX-M-1) were transferable by conjugation and belonged to incompatibility group IncI1, IncF, or IncN. Conclusions: The present study shows an increased frequency of ESBL-producing E. coli on farms with high consumption of third- or fourth-generation cephalosporins and indicates transfer of either ESBL-producing E. coli or plasmids between pigs and farmers.
    Journal of Antimicrobial Chemotherapy 06/2014; 69(10). DOI:10.1093/jac/dku180 · 5.31 Impact Factor
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    ABSTRACT: Emergence of antimicrobial resistance (AMR) in the animal reservoir forms a risk for human health. The use of antimicrobials in animals is the major cause of development of AMR in bacteria in animals. In the 1990s, the use of antimicrobials in animals, particularly as a growth promoter, led to alarming levels of AMR in many countries. This paper analyses the emergence of AMR in Denmark in terms of contributing factors that formed fertile ground from which AMR could develop. New technologies in combination with scientific unknowns led to the unexpected development of cross-resistance and an uncertainty about transmission to and risk for humans. Conflict of interests and varying susceptibility to risk between agriculture, health and commercial stakeholders complicated intervention. In addition, unintended economic incentives from old legislation resulted in a situation where the use of antimicrobials in general was stimulated. Complications of alarming high levels of AMR in animals, and a general discontent about this situation (including with farmers and vets) demanded a solution. National surveillance in DANMAP involving all stakeholders from the farm-to-fork food chain was setup to counteract scientific unknowns and conflicts of interest; new legislation was developed; and unintended economic incentives reduced. The current analysis may help to better understand the AMR problem in general and what may be done to counteract it.
    Food Control 06/2014; 40(1):185–192. DOI:10.1016/j.foodcont.2013.11.047 · 2.81 Impact Factor

Publication Stats

11k Citations
1,027.95 Total Impact Points


  • 2010–2015
    • National Food and Nutrition Institute
      Warszawa, Masovian Voivodeship, Poland
  • 2007–2015
    • Technical University of Denmark
      • • Center for Biological Sequence Analysis
      • • Division of Microbial Genomics and Epidemiology
      Lyngby, Capital Region, Denmark
    • Kuwait Institute for Scientific Research
      • Biotechnology
      Kuwait, Muhafazat al `Asimah, Kuwait
  • 2012
    • Northern Arizona University
      • Center for Microbial Genetics and Genomics
      Flagstaff, AZ, United States
  • 2011
    • Translational Genomics Research Institute
      Phoenix, Arizona, United States
    • Państwowy Instytut Weterynaryjny
      • Department of Microbiology
      Puławy, Lublin Voivodeship, Poland
  • 2009
    • University of Maiduguri
      • Faculty of Veterinary Medicine
      Maidugari, Borno, Nigeria
    • Centers for Disease Control and Prevention
      Атланта, Michigan, United States
  • 1995–2009
    • Danish Veterinary and Food Administration
      Glostrup, Capital Region, Denmark
  • 2006
    • Université de Montréal
      Montréal, Quebec, Canada
    • Ministry of Public Health, Thailand
      • Department of Medical Sciences
      Bangkok, Bangkok, Thailand
  • 2003
    • Statens Serum Institut
      København, Capital Region, Denmark
    • Chulalongkorn University
      • Faculty of Veterinary Science
      Krung Thep, Bangkok, Thailand
  • 1997–2001
    • Sydvestjysk Sygehus
      Esbjærg, South Denmark, Denmark
  • 2000
    • The Washington Institute
      Washington, Washington, D.C., United States