Antibiotics have revolutionized human and veterinary medicine and saved countless lives. Their discovery represented a quantum leap in the treatment of infectious diseases. However, unfortunately, the global emergence and steady increase of bacteria resistant to multiple antimicrobials have jeopardized their efficacy, to the extent that resistant strains have become a major public health threat. Moreover, there is rising concern that some bacterial infections may become untreatable in the future. Multiple factors have contributed to the present situation. One such factor, exemplified by the recent emergence and global spread of colistin resistance or of extended spectrum β-lactamases (ESBL), is the presence of resistance determinants on mobile genetic elements, such as plasmids and transposons, which are rapidly transmitted between the same and different bacterial species.

The use of colistin, discovered about 70 years ago, was discontinued in human medicine due to its systemic toxicity, but it has seen long-term application in veterinary medicine, mostly for the treatment of intestinal infections. Today, in the wake of increasing numbers of severe human infections caused by multidrug-resistant Gram-negative bacteria, colistin has become a key last resort drug. Recently, a plasmid-encoded colistin resistance determinant was isolated from an animal-associated Escherichia coli strain and subsequently found all over the world on multi-resistance plasmids from bacteria isolated from humans, animals, retail meat and environmental samples, threatening the continued effectiveness of colistin as an antibacterial agent. Similarly, the presence of ESBL-producing bacteria, which are found routinely in livestock and can degrade later-generation β-lactams, companion animals and aquatic environments, is becoming an increasing problem in human medicine.

Precisely how resistance determinants, the plasmids carrying them and their bacterial hosts are transmitted is poorly understood. It appears that individual bacterial strains are not only more frequently associated with resistance plasmids than others, but also seem to preferably colonize certain host species. Thus, they may serve as ‘transmission highways’ that rapidly lead to the worldwide dissemination of antimicrobial resistance. Improved understanding of these strains as potent transmitters and disseminators will facilitate the assessment of a particular strain’s risk potential, thereby helping to set up better-designed interventions that are more precisely targeted at preventing and reducing the transmission of antimicrobial resistance.

Unraveling such relationships and identifying the risk potential of individual bacterial strains are the key objectives of HECTOR, an interdisciplinary, multi-national research consortium funded for three years (budget 1.8 Million Euros) by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR) of the EU framework program Horizon2020. Using colistin resistance, ESBL-expressing plasmids and Escherichia coli as model systems, HECTOR (Host restriction of Escherichia Coli on Transmission dynamics and spread Of antimicrobial Resistance) brings together academic and public health research groups from Germany, the Netherlands, Spain and the United Kingdom from the fields of human and veterinary medicine, basic research and bioinformatics.

This ‘One Health’ initiative aims to identify genetic determinants that contribute to host restriction of Escherichia coli and their potential association with antimicrobial resistance transmission and prevalence. To this end, whole genome sequences from a large collection of Escherichia coli strains isolated from humans, animals and diverse environmental sources of different geographic origin (Europe and Vietnam) will be mined for genetic elements that correlate with host specificity or transmission dynamics. Factors flagged by this approach will be tested in experimental models in vitro and in vivo. Positively validated correlations will then be used to set up a mathematical model to predict host colonization and resistance transmission for a particular strain, thereby providing a risk assessment of that specific strain.

The VISAVET Health Surveillance Centre, specifically the Foodborne Zoonoses and Antimicrobial Resistance Unit (ZTA), includes the study of E. coli among other food-borne zoonoses (Salmonella, Campylobacter, Yersinia…). It is also responsible for analyzing antimicrobial resistance in zoonotic organisms, commensal bacteria of the intestinal tract or clinical isolates. The group has several lines of research on the characterization of important foodborne pathogens for Public Health and the mechanisms involved in the emergence and spread of antimicrobial resistance by using molecular tecniques as well as sequencing.

Partners in the HECTOR consortium:

• Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
  Constance Schultsz (Coordinator); Sebastien P. F. Matamoros; Boas C. L. van der Putten, M; Wiesje Zikkenheiner (Administrator)
• Institute of Microbiology and Epizootics, Freie Universität Berlin, Berlin, Germany
  Prof. Dr. Stefan Schwarz
• Institute of Molecular Pathogenesis, Friedrich-Loeffler-Institut, Jena, Germany
  Christian Menge; Marta Ferrandis Vila
• Junior Research Group 1: Microbial Genomics, Robert Koch Institute, Berlin, Germany
  Torsten Semmler
• VISAVET Health Surveillance Centre, Universidad Complutense of Madrid, Madrid, Spain
  María Ugarte Ruiz; Diego Flórez
• Centre for Tropical Medicine and Global health, Nuffield Department of Medicine Research Building, University of Oxford, Oxford, United Kingdom; Oxford Clinical Research Unit Viet Nam, Ho Chi Minh City, Viet Nam
  Hoa Thi Ngo; Trung Nguyen Vinh
• School of Veterinary Medicine, University of Surrey, Guildford, United Kingdom
  Roberto M. La Ragione; Amanda Fivian-Hughes; Jennifer Ritchie
• Mathematical Institute, Utrecht University, Utrecht, the Netherlands
  Martin C. J. Bootsma