https://orcid.org/0000-0002-4120-0530
On Tuesday, 2 August 2022, Josep (Pepe) Casadesús unexpectedly passed away while on vacation in his native Catalonia. Pepe was born on 11 September 1951, in his grandparents’ house, a small ‘masía’, in the municipality of Casserres, region of Catalonia, Spain. Pepe was trained as microbiologist at the ‘Estación Experimental del Zaidín-CSIC’ in Granada, Spain, working in the laboratory of José Olivares. He obtained his PhD degree in 1980 with a thesis on ‘Genetic studies in Rhizobium meliloti’. In 1983, after a 2-year stay at the ‘Nitrogen Fixation Laboratory’ of Ray Dixon at the University of Sussex (to learn molecular biology), he moved to the laboratory of John Roth at the University of Utah, in Salt Lake City, for a second postdoctoral period. John Roth’s lab had pioneered the use of Salmonella enterica (serovar Typhimurium) as a model organism for bacterial genetic studies. The charm and power of Salmonella genetics combined with the intellectual liveness of the lab would have an ever-lasting impact on Pepe’s scientific life. Not only did he adopt Salmonella as a model system for his subsequent studies, but he was also strongly inspired by the spirit and practices of Roth’s lab when he started his own group at the University of Seville in 1985. He never imposed experiments on his students, but preferred experimental strategies to take shape during open and friendly discussions, only occasionally animated by his persuasive skills. He returned to Utah as a visiting professor for two extended periods of time, in 1988 and in 2000. Besides enjoying the company of some faculty at the Biology Department, he loved the magnificent decor of Salt Lake City mountains. He especially liked taking walks in Red Butte Canyon, at the eastern edge of the University campus, where colour changes in the fall can overwhelm your senses (Fig. 1). After two other stays as visiting professor at the Biozentrum, Universität Basel (Switzerland) and at the Università degli Studi di Sassari (Sardinia, Italy), in 1999, Pepe became full Professor of Genetics at the University of Seville, where he stayed for the rest of his career. He received many distinctions related to his academic activity, but undoubtedly what was most rewarding for him was the appreciation and respect he received from his former students and alumni. He trained many researchers in his lab and his lectures inspired many students to undertake a career in science. Pepe was the editor of several journals like PLoS Genetics (from 2011) and was the ambassador of the American Society for Microbiology in Europe. In 2018, he was elected fellow of the American Academy of Microbiology and in 2019 of the European Academy for Microbiology. He did extensive work as reviewer of papers and grant proposals for institutions in the USA, Ibero-America, and the European Commission.
Pepe in Red Butte Canyon, UT, October 2014.
In his nearly 40 years of activity, Pepe’s research covered various aspects of Salmonella biology. Early on, he became fascinated by the mechanisms that produce phenotypic heterogeneity in populations of genetically identical bacteria, a topic that constituted a leitmotif in his scientific career. This interest, which he developed long before the subject became trendy, led him to focus on epigenetic regulation, particularly the role of DNA methylation in the inheritance of cell-to-cell differences. He described the involvement of DNA-methyl transferases in some key processes underlying Salmonella lifestyle inside and outside the animal host. These include phase-variation mechanisms that control fimbrial and LPS expression and their effects on bacterial invasiveness, intracellular growth, and resistance to bile salts. Some of these topics were the basis of a long and fruitful collaboration with one of us (FGdP), leading to the discovery of pathogen functions that attenuate the growth inside the host cell and facilitate persistence. One of these functions, which we first identified in S. Typhimurium and named ‘Intracellular growth attenuator-A’ (IgaA), turned out to be a master regulator (repressor) of the Rcs phosphorelay, which responds to insults affecting envelope homeostasis. IgaA proved to be essential to allow Rcs activity only under stress conditions and this negative regulation was shown to be central for pathogenicity. Among other qualities, Pepe was particularly generous in sharing materials generated in his lab and his enthusiasm for the success of others. FGdP and his coworkers will always be grateful to him for providing a merodiploid S. Typhimurium strain, which by using an ‘unconventional’ genetic trick, allowed the discovery of a hitherto unknown pathogen-specific penicillin-binding protein (PBP) involved in cell division. This strain, initially constructed in Pepe’s lab to facilitate mutation mapping in Salmonella by analysis of segregants, helped to reveal the existence of alternative morphogenetic proteins in the same bacterium.
Pepe described several examples of bimodal expression patterns of Salmonella virulence functions, including those related to outer membrane and LPS biogenesis. Of particular note is the demonstration that bimodal expression of the opvAB locus, which controls LPS O-antigen side-chain length, generates lineages that are resistant to bacteriophage infection but concomitantly lose virulence potential. Further studies carried out with his collaborator Maria Antonia Sanchez-Romero, corroborated the notion that phenotypic bistability can facilitate bacterial adaptation to hostile environments (like those encountered by Salmonella during host infection) through either a division of labour or a bet hedging strategy. Last but not least, in all his research endeavours, Pepe had the ability to see the big picture, make a synthesis and write about it in a clear and precise way. Testimony of his talent as a writer is the fact that 8 out of 10 of his most cited articles are review articles or commentaries.
Aside from his scientific achievements, and his legacy as a teacher, Pepe will be remembered and missed for his extraordinarily rich personality and humanity. He had a special talent for perceiving the subtleties that characterize different cultures (even within a given country). He enjoyed blending into these cultures by speaking their languages—besides Catalan, Castellan Spanish, and English, he was fluent in Italian and French (he read books and gave seminars in all these languages)—or indulging in more epicurean activities like eating a local specialty at a restaurant, accompanied by a glass (or more) of carefully selected local wine. He had a legendary penchant for fine food and drinks. In his sporadic visits to some of us in France, he became friend with two separate wine sellers in our town and would spend an incredible amount of time discussing wine making and tasting them. He proudly used to tell the story of how he had won a privately organized wine tasting contest by identifying the ‘Vermentino di Gallura’, a little-known delicious Sardinian white wine. But Pepe’s passion for life went far beyond the earthy pleasures; he was a voracious reader of all sorts of literature and a scholar in epistemology, particularly proud to have been the Spanish translator of ‘Mind from Matter?’, Max Delbrück’s philosophical testament. He loved listening to and sharing music. Some of us still have several cassette tapes with his handwriting on the label, that he had recorded for us from vinyl records during his postdoc days in Utah. His love for sharing included Gary Larson’s cartoons, that he would include in his e-mails regularly (as a constant reminder of the irony in life) and the photographs that he would take during his trips. Besides nature and landscapes, he had an unusual interest in taking pictures of commercial airplanes on runways, possibly as symbols of his passion for traveling. This photo-taking activity would reach its climax during his occasional road trips to Gibraltar with his wife, Laura. As it turns out, Gibraltar airport main runway intersects Winston Churchill Avenue, a regular road, and the traffic of planes and cars alternates at the rhythm of a traffic light…
We cannot end this tribute to Pepe, without expressing our empathy to his wife Laura and daughter Sara in this difficult time. Pepe has left and immense and rich legacy to all of us and we should be thankful for those enjoyable occasions that we shared with him.
