Acinetobacter baumannii est un pathogène opportuniste qui prend une importance clinique croissante du fait de l’acquisition de multi-résistance. Nous avons étudié chez A. baumannii les caractéristiques et la régulation des intégrons de classe 1 (IM1) qui sont des systèmes génétiques favorisant l’acquisition, l’expression et la dissémination des gènes de résistance aux antibiotiques. Nous avons montré qu’il existe une prédominance des promoteurs des cassettes Pc fort in vivo dans une collection d’isolats cliniques et d’environnement hospitalier et in silico dans les IM1 chez A. baumannii. Nous avons aussi montré que l’expression des Pc chez A. baumannii est 4 fois plus faible que chez E. coli, quel que soit le variant de Pc. Deux explications sont possibles pour la sélection des Pc forts chez A. baumannii : (i) la nécessité d’avoir un niveau d’expression suffisant en clinique pour survivre à la pression de sélection antibiotique et (ii) la nécessité d’une régulation de l’expression de l’intégrase, représentant un coût biologique important. En effet, A. baumannii ne possède pas le système de répression par LexA existant chez E. coli. Nos résultats ouvrent le champ de l’étude de la régulation des IM1 chez A. baumannii et ainsi l’identification de nouvelles voies d’action pour lutter contre l’antibio-résistance / Acinetobacter baumannii is an opportunistic pathogen of increasing clinical importance due to the acquisition of multi-resistance. We studied in A. baumannii the characteristics and regulation of class 1 integrons (IM1), which are genetic systems that favor the acquisition, expression and dissemination of antibiotic resistance genes. We have shown that there is a predominance of strong Pc cassette promoters, in vivo, in a collection of clinical and hospital environment isolates, and in silico, from A. baumannii IM1 published in NCBI. We have also shown that the expression of Pc in A. baumannii is 4-fold lower than in E. coli, regardless of the Pc variant. Explanations that can be raised for the selection of strong Pc in A. baumannii are: (i) the need for a sufficient level of antibiotic resistance expression to survive the selection pressure in clinical environment; and (ii) the need for regulation of the integrase expression, which is of significant biological cost. Indeed A. baumannii does not have the LexA repression system existing in E. coli. Our results open the field of the study of IM1 regulation in A. baumannii and thus the identification of new pathways to fight antibiotic resistance.

Drosophila melanogaster has been integral to unravelling the mechanisms of animalian immunity. Diverse species of Drosophila with sequenced genomes have been used to characterize how immune systems respond to natural selection. However, Drosophila is an incredibly speciose lineage, especially so in the subgenus Drosophila. Of the 12 genomes sequenced in 2007, ushering in the era of Drosophila comparative genomics, only three were subgenus Drosophila flies, and none were from the lesser- characterized Immigrans-Tripunctata clade. Recently, multiple Immigrans-Tripunctata clade Drosophila have been sequenced, including the transcriptome of Drosophila neotestacea. I investigated the realized immune responses of D. neotestacea to characterize the immune repertoire of this divergent lineage. The signalling pathways of D. neotestacea were largely conserved, though there were interesting patterns of evolution in antimicrobial peptide genes (AMPs). One of these AMPs, a diptericin, was highly dissimilar to diptericins in D. melanogaster, and conserved in other subgenus Drosophila flies. This prompted me to characterize the evolution of the diptericin gene family in Drosophila. I found that Drosophila diptericins have evolved under positive selection, and display intriguing differences in net charge to well-conserved diptericin domains. I assessed the expression profile of this divergent D. neotestacea diptericin, and found that it did not respond to Serratia bacterial challenge, unlike diptericin in D. melanogaster. I also highlight a potential novel drosocin-like AMP conserved throughout the subgenus Drosophila. These results agree that signalling pathways are highly conserved in diverse insects, including Drosophila. However seemingly-conserved effectors of the Drosophila immune response (such as AMPs) may have previously unappreciated variation in expression and function. / Graduate / 0718 / 0353 / 0369 / markhans@uvic.ca