Survival of Anaerobic Fe²⁺ Stress Requires the ClpXP Protease.

Shewanella oneidensis strain MR-1 is a versatile bacterium capable of respiring extracellular, insoluble ferric oxide minerals under anaerobic conditions. The respiration of iron minerals results in the production of soluble ferrous ions, which at high concentrations are toxic to living organisms. It is not fully understood how Fe²⁺ is toxic to cells anaerobically, nor is it fully understood how S. oneidensis is able to resist high levels of Fe²⁺ Here we describe the results of a transposon mutant screen and subsequent deletion of the genes clpX and clpP in S. oneidensis, which demonstrate that the protease ClpXP is required for anaerobic Fe²⁺ resistance. Many cellular processes are known to be regulated by ClpXP, including entry into stationary phase, envelope stress response, and turnover of stalled ribosomes. However, none of these processes appears to be responsible for mediating anaerobic Fe²⁺ resistance in S. oneidensis Protein trapping studies were performed to identify ClpXP targets in S. oneidensis under Fe²⁺ stress, implicating a wide variety of protein targets. Escherichia coli strains lacking clpX or clpP also display increased sensitivity to Fe²⁺ anaerobically, indicating Fe²⁺ resistance may be a conserved role for the ClpXP protease system. Hypotheses regarding the potential role(s) of ClpXP during periods of high Fe²⁺ are discussed. We speculate that metal-containing proteins are misfolded under conditions of high Fe²⁺ and that the ClpXP protease system is necessary for their turnover.IMPORTANCE Prior to the evolution of cyanobacteria and oxygenic photosynthesis, life arose and flourished in iron-rich oceans. Today, aqueous iron-rich environments are less common, constrained to low-pH conditions and anaerobic systems such as stratified lakes and seas, digestive tracts, subsurface environments, and sediments. The latter two ecosystems often favor dissimilatory metal reduction, a process that produces soluble Fe²⁺ from iron oxide minerals. Dissimilatory metal-reducing bacteria must therefore have mechanisms to tolerate anaerobic Fe²⁺ stress, and studying resistance in these organisms may help elucidate the basis of toxicity. Shewanella oneidensis is a model dissimilatory metal-reducing bacterium isolated from metal-rich sediments. Here we demonstrate a role for ClpXP, a protease system widely conserved in bacteria, in anaerobic Fe²⁺ resistance in both S. oneidensis and Escherichia coli.

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