Julian Davies and the discovery of kanamycin resistance transposon Tn5

Abstract

This paper recounts some of my fond memories of a collaboration between Julian Davies and myself that started in 1974 in Geneva and that led to our serendipitous discovery of the bacterial kanamycin resistance transposon Tn5, and aspects of the lasting positive impact of our interaction and discovery on me and the community. Tn5 was one of the first antibiotic resistance transposons to be found. Its analysis over the ensuing decades provided valuable insights into mechanisms and control of transposition, and led to its use as a much-valued tool in diverse areas of molecular genetics, as also will be discussed here. The Journal of Antibiotics (2017) 70, 339-346; doi:10.1038/ja.2016.120; published online 12 October 2016 BACKGROUND It was wonderfully educational, productive and exciting for me to work with Julian Davies for a few years in the mid 1970s, doing experiments that led to the serendipitous discovery and initial characterizations of kanamycin resistance transposon Tn5 1 -one of the first and most useful of the many bacterial antibiotic resistance (AR) transposons that have been found. 2 I was inspired by Julian's knowledge of mechanisms of antibiotic action and resistance mechanisms, his creativity and clarity of thought and expression, as illustrated in his numerous papers, 3-6 and by his high energy, kindness and inventive good humor-traits that have enriched the lives and careers of many people over the years. Described here, in tribute to Julian and his special character, are my memories of a collaboration that led to Tn5's unexpected discovery, Tn5's properties, and some lasting impacts of our collaboration on the field and on me personally.We began interacting in 1974, soon after Julian arrived in Geneva to begin his sabbatical with Pierre Francois Spahr (Department of Molecular Biology of the University). 7 I was then in my fourth (final) year as Chargé de Recherche (senior postdoc) in Lucien Caro's group in the same department, studying λdv plasmids, often in collaboration with Grete Kellenberger-Gujer, also in Lucien's group 8-13 -and during these years, also hugely enjoying features in and out of the lab that have drawn researchers to Geneva for decades: a superb scientific atmosphere, year-round easy access to the exquisite Alps and Jura mountains, and the language, cuisine and culture of Geneva and vicinity. I had become intrigued the year before by Julian's ideas about origins and evolution of resistance genes, as described in his paper with Raoul Benveniste. 14 They advanced the then-novel theory that the types of bacteria that had provided life saving antibiotics were also the ancestral sources of AR genes that were becoming increasingly common in human and veterinary pathogens. Their inferences were

Emerging Approaches to Profile Accessible Chromatin from Formalin-Fixed Paraffin-Embedded Sections

“…Tn5 transposase was first discovered in the 1970s based on the kanamycin resistance it conferred to host bacteria [ 63 , 64 ]. In addition to providing a mechanistic model for transposases, Tn5 (106 kDa active dimer) has become an invaluable molecular tool [ 65 ].…”

Emerging Approaches to Profile Accessible Chromatin from Ffpe Sections

“…Tn5 transposase was first discovered in the 1970s based on the kanamycin resistance it conferred to host bacteria 57,58 . In addition to providing a mechanistic model for transposases, Tn5 (106 kDa active dimer) has proven an invaluable molecular tool 59 .…”