Chromosomal antioxidant genes have metal ion-specific roles as determinants of bacterial metal tolerance

• Published in: Environmental microbiology 2009-10, Vol.11 (10), p.2491-2509
• Main Authors: Harrison, Joe J, Tremaroli, Valentina, Stan, Michelle A, Chan, Catherine S, Vacchi-Suzzi, Caterina, Heyne, Belinda J, Parsek, Matthew R, Ceri, Howard, Turner, Raymond J
• Format: Article
• Language: English
• Subjects: Adaptation, Physiological - genetics; Anions - chemistry; Antioxidants - metabolism; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Cations - chemistry; Chromosomes, Bacterial - genetics; Escherichia coli; Escherichia coli - chemistry; Escherichia coli - genetics; Escherichia coli - metabolism; Escherichia coli Proteins - genetics; Escherichia coli Proteins - metabolism; Gene Expression Regulation, Bacterial; Genes, Bacterial; Metals - chemistry; Metals - metabolism; Oxidation-Reduction; Repressor Proteins - genetics; Repressor Proteins - metabolism; Superoxide Dismutase - genetics; Superoxide Dismutase - metabolism; Thioredoxins - genetics; Thioredoxins - metabolism
• ISSN: 1462-2912; 1462-2920
• DOI: 10.1111/j.1462-2920.2009.01973.x

Microbiological metal toxicity involves redox reactions between metal species and cellular molecules, and therefore, we hypothesized that antioxidant systems might be chromosomal determinants affecting the susceptibility of bacteria to metal toxicity. Here, survival was quantified in metal ion-exposed planktonic cultures of several Escherichia coli strains, each bearing a mutation in a gene important for redox homeostasis. This characterized ~250 gene-metal combinations and identified that sodA, sodB, gor, trxA, gshA, grxA and marR have distinct roles in safeguarding or sensitizing cells to different toxic metal ions (Cr₂O₇²⁻, Co²⁺, Cu²⁺, Ag⁺, Zn²⁺, AsO₂⁻, SeO₃²⁻ or TeO₃²⁻). To shed light on these observations, fluorescent sensors for reactive oxygen species (ROS) and reduced thiol (RSH) quantification were used to ascertain that different metal ions exert oxidative toxicity through disparate modes-of-action. These oxidative mechanisms of metal toxicity were categorized as involving ROS and thiol-disulfide chemistry together (AsO₂⁻, SeO₃²⁻), ROS predominantly (Cu²⁺, Cr₂O₇²⁻) or thiol-disulfide chemistry predominantly (Ag⁺, Co²⁺, Zn²⁺, TeO₃²⁻). Corresponding to this, promoter-luxCDABE fusions showed that toxic doses of different metal ions up- or downregulate the transcription of gene sets marking distinct pathways of cellular oxidative stress. Altogether, our findings suggest that different metal ions are lethal to cells through discrete pathways of oxidative biochemistry, and moreover, indicate that chromosomally encoded antioxidant systems may have metal ion-specific physiological roles as determinants of bacterial metal tolerance.