A Matter of Timing: Contrasting Effects of Hydrogen Sulfide on Oxidative Stress Response in Shewanella oneidensis

Abstract

Hydrogen sulfide (H 2 S), well known for its toxic properties, has recently become a research focus in bacteria, in part because it has been found to prevent oxidative stress caused by treatment with some antibiotics. H 2 S has the ability to scavenge reactive oxygen species (ROS), thus preventing oxidative stress, but it is also toxic, leading to conflicting reports of its effects in different organisms. Here, with Shewanella oneidensis as a model, we report that the effects of H 2 S on the response to oxidative stress are time dependent. When added simultaneously with H 2 O 2 , H 2 S promoted H 2 O 2 toxicity by inactivating catalase, KatB, a hemecontaining enzyme involved in H 2 O 2 degradation. Such an inhibitory effect may apply to other heme-containing proteins, such as cytochrome cbb 3 oxidase. When H 2 O 2 was supplied 20 min or later after the addition of H 2 S, the oxidative-stress-responding regulator OxyR was activated, resulting in increased resistance to H 2 O 2 . The activation of OxyR was likely triggered by the influx of iron, a response to lowered intracellular iron due to the iron-sequestering property of H 2 S. Given that Shewanella bacteria thrive in redox-stratified environments that have abundant sulfur and iron species, our results imply that H 2 S is more important for bacterial survival in such environmental niches than previously believed. IMPORTANCE Previous studies have demonstrated that H 2 S is either detrimental or beneficial to bacterial cells. While it can act as a growth-inhibiting molecule by damaging DNA and denaturing proteins, it helps cells to combat oxidative stress. Here we report that H 2 S indeed has these contrasting biological functions and that its effects are time dependent. Immediately after H 2 S treatment, there is growth inhibition due to damage of heme-containing proteins, at least to catalase and cytochrome c oxidase. In contrast, when added a certain time later, H 2 S confers an enhanced ability to combat oxidative stress by activating the H 2 O 2 -responding regulator OxyR. Our data reconcile conflicting observations about the functions of H 2 S.

The cytochrome bd oxidase of Escherichia coli prevents respiratory inhibition by endogenous and exogenous hydrogen sulfide

“…Thiol compounds bind with substantial avidity to soft metals and hemes and therefore are potentially inhibitory to enzymes that use these cofactors (Nies, 2003, Wu et al, 2015, Vitvitsky et al, 2015, Bolic et al, 2015, Nagy, 2015). Zinc has a moderate affinity for thiols, and zinc enzymes can be inhibited when moderate concentrations of cysteine or sulfide coordinate and perhaps extract the metal (Martin & Maricle, 2015, Gu & Imlay, 2013).…”

“…Such changes were observed among fish that live in sulfidic waters and plants that must tolerate sulfide exudations from sediments during flooding. Intriguingly, a cytochrome c oxidase in a sulfate-reducing bacterium appeared to be tolerant of 0.25 mM sulfide, but the structural basis was not explored (Wu et al, 2015). …”

“…Like cysteine, sulfide is chemically reactive and potentially problematic. It exhibits a substantial affinity for heme and for soft metals, including those in proteins (Wu et al , 2015, Vitvitsky et al , 2015, Bolic et al , 2015, Nagy, 2015). Due to its tiny size, sulfide cannot easily be physically excluded from their active sites.…”

Reduced Glutathione Mediates Resistance to H 2 S Toxicity in Oral Streptococci

“…It has been reported that H 2 S elicited microbicidal effects by inhibiting the activities of superoxide dismutase and catalase (10,27). In addition, high levels of sulfide impose survival stress on Desulfovibrio vulgaris by sequestering essential trace metals (28).…”

Mechanism of H 2 S-mediated protection against oxidative stress in Escherichia coli

“…The latter function of H 2 S seems to be universal, because it has been implicated in bacterial defense against reactive oxygen species (ROS) and antibiotics-induced oxidative damage (2). H 2 S can also kill microorganisms by inhibiting antioxidant enzymes during induced oxidative stress (3,4). These seemingly contradictory attributes of H 2 S highlight its concentration-dependent dual nature: at high concentration, it is a toxic gas, and at lower physiological concentrations, it is a signaling and/or protective molecule.…”