Divergent transcriptional responses to physiological and xenobiotic stress in Giardia duodenalis

Ansell, BR; McConville, MJ; Baker, L; Korhonen, PK; Emery, SJ; Svard, SG; Gasser, RB; Jex, AR

Author(s): Ansell, BR; McConville, MJ; Baker, L; Korhonen, PK; Emery, SJ; Svard, SG; Gasser, RB; Jex, AR;
Details: Publication Year 2016-07-25,Volume 60,Issue #10,Page 6034-6045
Journal Title: Antimicrobial Agents and Chemotherapy
Publication Type: Journal Article
Abstract: Understanding how parasites respond to stress can help to identify essential biological processes. Giardia duodenalis is a parasitic protist that infects the human gastrointestinal tract and causes 200-300 million cases of diarrhoea annually. Metronidazole, a major antigiardial drug, is though to cause oxidative damage within the infective trophozoite form. However, treatment efficacy is sub-optimal, due partly to metronidazole-resistant infections. To elucidate conserved and stress-specific responses, we calibrated sub-lethal metronidazole, hydrogen peroxide and thermal stresses to exert approximately equal pressure on trophozoite growth, and compared transcriptional responses after 24 hours of exposure. We identified 252 genes that were differentially transcribed in response to all three stressors, including glycolytic and DNA repair enzymes, a MAP kinase, high-cysteine membrane proteins, FAD synthetase, and histone modification enzymes. Transcriptional responses appeared to diverge according to physiological or xenobiotic stress. Down-regulation of the antioxidant system and alpha-giardins was observed only under metronidazole-induced stress, whereas up-regulation of GARP-like transcription factors and their subordinate genes was observed in response to hydrogen peroxide and thermal stressors. Limited evidence was found in support of stress-specific response elements upstream of differentially transcribed genes; however, antisense de-repression and differential regulation of RNA interference machinery suggest multiple epigenetic mechanisms of transcriptional control.
Publisher: Am Soc Microbiology
Research Division(s): Population Health And Immunity
PubMed ID: 27458219
Link To PubMed Central Version: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5038253/
Publisher's Version: https://doi.org/10.1128/AAC.00977-16
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2016-08-10 04:12:49

Last Modified: 2018-07-04 03:28:35