title: Metabolomic investigation of the bacterial response to a metal challenge.
abstract: Pseudomonas pseudoalcaligenes KF707 is naturally resistant to the toxic metalloid tellurite, but the mechanisms of resistance are not known. In this study we report the isolation of a KF707 mutant (T5) with hyperresistance to tellurite. In order to characterize the bacterial response and the pathways leading to tolerance, we utilized Phenotype MicroArray technology (Biolog) and a metabolomic technique based on nuclear magnetic resonance spectroscopy. The physiological states of KF707 wild-type and T5 cells exposed to tellurite were also compared in terms of viability and reduced thiol content. Our analyses showed an extensive change in metabolism upon the addition of tellurite to KF707 cultures as well as different responses when the wild-type and T5 strains were compared. Even in the absence of tellurite, T5 cells displayed a "poised" physiological status, primed for tellurite exposure and characterized by altered intracellular levels of glutathione, branched-chain amino acids, and betaine, along with increased resistance to other toxic metals and metabolic inhibitors. We conclude that hyperresistance to tellurite in P. pseudoalcaligenes KF707 is correlated with the induction of the oxidative stress response, resistance to membrane perturbation, and reconfiguration of cellular metabolism.
authors.affiliation: Department of Biological Sciences, University of Calgary, Alberta, Canada.
authors.forename: Valentina
authors.initials: V
authors.lastname: Tremaroli
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Workentine
authors.forename: Aalim M
authors.initials: AM
authors.lastname: Weljie
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Vogel
authors.forename: Howard
authors.initials: H
authors.lastname: Ceri
authors.forename: Carlo
authors.initials: C
authors.lastname: Viti
authors.forename: Enrico
authors.initials: E
authors.lastname: Tatti
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Hynes
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Turner
authors.forename: Davide
authors.initials: D
authors.lastname: Zannoni
mesh_terms: D003593:Cytoplasm / Q000737:chemistry; D024881:Drug Resistance, Bacterial; D009682:Magnetic Resonance Spectroscopy; D055432:Metabolomics; D050296:Microbial Viability; D044205:Pseudomonas pseudoalcaligenes / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000032:analysis; D013691:Tellurium / Q000633:toxicity*
chemical_list: D013438:Sulfhydryl Compounds; C026660:tellurous acid; D013691:Tellurium