Caenorhabditis elegans as a Convenient Animal Model for Microbiome Studies.

Microbes constitute the most prevalent life form on Earth, yet their remarkable diversity remains mostly unrecognized. Microbial diversity in vertebrate models presents a significant challenge for investigating host-microbiome interactions. The model organism Caenorhabditis elegans has many advantages for delineating the effects of host genetics on microbial composition. In the wild, the C. elegans gut contains various microbial species, while in the laboratory it is usually a host for a single bacterial species. There is a potential host-microbe interaction between microbial metabolites, drugs, and C. elegans phenotypes. This mini-review aims to summarize the current understanding regarding the microbiome in C. elegans. Examples using C. elegans to study host-microbe-metabolite interactions are discussed.

Hepatocellular carcinoma after treatment cessation in non-cirrhotic HBeAg-negative chronic hepatitis B: A multicentre cohort study.

BACKGROUND AND AIMS: Scarce data exist on the effect of nucleos(t)ide analogue (NA) discontinuation on hepatocellular carcinoma (HCC) risk in HBeAg-negative chronic hepatitis B (CHBe-). Therefore, we assessed whether HCC risk is increased in non-cirrhotic CHBe- patients who discontinue compared to those remaining on NAs. METHODS: This cohort study included 650 consecutive non-cirrhotic Caucasian or Asian patients with CHBe- without a history of HCC who discontinued NAs after a median of 5 or 3 years (cases, n = 325; Caucasians: 143, Asians: 182) or remained on NA therapy beyond 5 or 3 years respectively (controls, n = 325; Caucasians: 223, Asians: 102). Propensity score (PS) 1:1 matching was applied to adjust for patients' origin, age and sex. RESULTS: During a median follow-up of 44 months, HCC developed in 7/325 cases and 9/325 controls or 7/245 PS-matched cases and 7/245 PS-matched controls with 5-year cumulative HCC incidence of 5.1% and 4.9% respectively (log-rank, P = .836). No difference in 5-year HCC risk was observed between cases and controls of Caucasian (3.0% vs 4.8%; log-rank, P = .510) or Asian origin (1.3% vs 2.2%; log-rank, P = .873). In both cases and controls, HCC incidence was independently associated with age and PAGE-B score. In cases alone, HCC development after NA discontinuation was associated only with pretreatment platelet counts and PAGE-B score, but not with any type of relapse or HBsAg loss. CONCLUSIONS: Our findings suggest that discontinuation of effective long-term NA therapy in non-cirrhotic CHBe- patients are not associated with increased HCC risk, which is not affected by post-NA relapses and/or HBsAg loss.

Redox and Metabolic Regulation of Intestinal Barrier Function and Associated Disorders.

The intestinal epithelium forms a physical barrier assembled by intercellular junctions, preventing luminal pathogens and toxins from crossing it. The integrity of tight junctions is critical for maintaining intestinal health as the breakdown of tight junction proteins leads to various disorders. Redox reactions are closely associated with energy metabolism. Understanding the regulation of tight junctions by cellular metabolism and redox status in cells may lead to the identification of potential targets for therapeutic interventions. In vitro and in vivo models have been utilized in investigating intestinal barrier dysfunction and in particular the free-living soil nematode, Caenorhabditis elegans, may be an important alternative to mammalian models because of its convenience of culture, transparent body for microscopy, short generation time, invariant cell lineage and tractable genetics.

Glucose-6-Phosphate Dehydrogenase, Redox Homeostasis and Embryogenesis.

Normal embryogenesis requires complex regulation and precision, which depends on multiple mechanistic details. Defective embryogenesis can occur by various mechanisms. Maintaining redox homeostasis is of importance during embryogenesis. NADPH, as produced from the action of glucose-6-phosphate dehydrogenase (G6PD), has an important role in redox homeostasis, serving as a cofactor for glutathione reductase in the recycling of glutathione from oxidized glutathione and for NADPH oxidases and nitric oxide synthases in the generation of reactive oxygen (ROS) and nitrogen species (RNS). Oxidative stress differentially influences cell fate and embryogenesis. While low levels of stress (eustress) by ROS and RNS promote cell growth and differentiation, supra-physiological concentrations of ROS and RNS can lead to cell demise and embryonic lethality. G6PD-deficient cells and organisms have been used as models in embryogenesis for determining the role of redox signaling in regulating cell proliferation, differentiation and migration. Embryogenesis is also modulated by anti-oxidant enzymes, transcription factors, microRNAs, growth factors and signaling pathways, which are dependent on redox regulation. Crosstalk among transcription factors, microRNAs and redox signaling is essential for embryogenesis.

PhoPQ two-component regulatory system plays a global regulatory role in antibiotic susceptibility, physiology, stress adaptation, and virulence in Stenotrophomonas maltophilia.

BACKGROUND: Stenotrophomonas maltophilia, an opportunistic pathogen, is ubiquitously present in various environments, signifying its high capability of environmental adaptation. Two-component regulatory system (TCS) is a powerful implement to help organisms to survive in different environments. In clinic, treatment of S. maltophilia infection is difficult because it is naturally resistant to many antibiotics, highlighting the necessity to develop novel drugs or adjuvants. Given their critical and extensively regulatory role, TCS system has been proposed as a convincing target for novel drugs or adjuvants. PhoPQ TCS, a highly conserved TCS in several pathogens, plays crucial roles in low-magnesium adaption, polymyxin resistance, and virulence. In this study, we aimed to characterize the role of PhoPQ TCS of S. maltophilia in antibiotic susceptibility, physiology, stress adaptation, and virulence. RESULTS: To characterize PhoPQ system, phoP single mutant as well as phoP and phoQ double mutant were constructed. Distinct from most phoPQ systems of other microorganisms, two features were observed during the construction of phoP and phoQ single deletion mutant. Firstly, the phoQ mutant was not successfully obtained. Secondly, the compromised phenotypes of phoP mutant were not reverted by complementing an intact phoP gene, but were partially restored by complementing a phoPQ operon. Thus, wild-type KJ, phoP mutant (KJΔPhoP), phoPQ mutant (KJΔPhoPQ), and complemented strain (KJΔPhoPQ (pPhoPQ)) were used for functional assays, including antibiotic susceptibility, physiology (swimming motility and secreted protease activity), stress adaptation (oxidative, envelope, and iron-depletion stresses), and virulence to Caenorhabditis elegans. KJΔPhoPQ totally lost swimming motility, had enhanced secreted protease activity, increased susceptibility to antibiotics (ß-lactam, quinolone, aminoglycoside, macrolide, chloramphenicol, and sulfamethoxazole/ trimethoprim), menadione, H2O2, SDS, and 2,2'-dipyridyl, as well as attenuated virulence to C. elegans. Trans-complementation of KJΔPhoPQ with phoPQ reverted these altered phenotypes to the wild-type levels. CONCLUSIONS: Given the critical and global roles of PhoPQ TCS in antibiotic susceptibility, physiology, stress adaptation, and virulence, PhoPQ is a potential target for the design of drugs or adjuvants.

tert-Butyl Hydroperoxide (tBHP)-Induced Lipid Peroxidation and Embryonic Defects Resemble Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency in C. elegans.

G6PD is required for embryonic development in animals, as severe G6PD deficiency is lethal to mice, zebrafish and nematode. Lipid peroxidation is linked to membrane-associated embryonic defects in Caenorhabditis elegans (C. elegans). However, the direct link between lipid peroxidation and embryonic lethality has not been established. The aim of this study was to delineate the role of lipid peroxidation in gspd-1-knockdown (ortholog of g6pd) C. elegans during reproduction. tert-butyl hydroperoxide (tBHP) was used as an exogenous inducer. Short-term tBHP administration reduced brood size and enhanced germ cell death in C. elegans. The altered phenotypes caused by tBHP resembled GSPD-1 deficiency in C. elegans. Mechanistically, tBHP-induced malondialdehyde (MDA) production and stimulated calcium-independent phospholipase A2 (iPLA) activity, leading to disturbed oogenesis and embryogenesis. The current study provides strong evidence to support the notion that enhanced lipid peroxidation in G6PD deficiency promotes death of germ cells and impairs embryogenesis in C. elegans.

Epidemiological profiles and pathogenicity of Vancomycin-resistant Enterococcus faecium clinical isolates in Taiwan.

The emerging Vancomycin-resistant Enterococcus faecium (VRE-fm) is an opportunistic pathogen causing nosocomial infections. The identification of VRE-fm is important for successful prevention and control in healthcare settings. VRE-fm clinical isolates obtained from regional hospitals in northern Taiwan were characterized for antimicrobial susceptibility, virulence genes and biofilm production. Most isolates exhibited multi-drug resistance and carried the virulence genes, esp and hyl. While all isolates produce biofilms, those isolates that carried esp exhibited greater biofilm production. Isolates with different virulence gene carriages were examined for pathogenicity by using a nematode model, Caenorhabditis elegans, for determining microbial-host interactions. The survival assay showed that C. elegans was susceptible to Linezolid-resistant VRE-fm isolates with hyl. Combining the molecular epidemiological profiles regarding pathogenesis in C. elegans can serve as a guide for physicians in limiting opportunistic infections caused by VRE-fm.

Impaired immune response and barrier function in GSPD-1-deficient C. elegans infected with Klebsiella pneumoniae.

gspd-1-RNAi knockdown Caenorhabditis elegans was used as an immune-compromised model to investigate the role of G6PD in host-pathogen interactions. A shorted lifespan, increased bacterial burden and bacterial translocation were observed in gspd-1-knockdown C. elegans infected with Klebsiella pneumoniae (KP). RNAseq revealed that the innate immune pathway, including clc-1 and tsp-1, was affected by gspd-1 knockdown. qPCR confirmed that tight junction (zoo-1, clc-1) and immune-associated genes (tsp-1) were down-regulated in gspd-1-knockdown C. elegans and following infection with KP. The down-regulation of antimicrobial effector lysozymes, including lys-1, lys-2, lys-7, lys-8, ilys-2 and ilys-3, was found in gspd-1-knockdown C. elegans infected with KP. Deletion of clc-1, tsp-1, lys-7, and daf-2 in gspd-1-knockdown C. elegans infected with KP abolished the shorten lifespan seen in the Mock control. GSPD-1 deficiency in C. elegans resulted in bacterial accumulation and lethality, possibly due to a defective immune response. These findings indicate that GSPD-1 has a protective role in microbial defense in C. elegans by preventing bacterial colonization through bacterial clearance.

The role of EII complex in the bacterial responses to the glucose-survey in clinical Klebsiella pneumoniae isolates.

Type 3 fimbriae in Klebsiella pneumoniae are important for bacterial colonization on abiotic and biotic surfaces. The major subunit of type 3 fimbriae (MrkA) is increased by overexpression of EtcABC, an EII complex of phosphoenolpyruvate:carbohydrate phosphotransferase systems (PTSs), through cAMP-cAMP receptor protein (cAMP-CRP) in K. pneumoniae STU1. Here, we further characterized the relations between the amount of etcABC mRNA and MrkA in 78 clinical K. pneumoniae isolates incubated in high levels of glucose. By Western blotting, we observed that MrkA of 29 isolates were not decreased much by high levels of glucose (Group A) but MrkA of other 49 isolates were significantly reduced (Group B) in the same condition. The bacterial biofilms on abiotic surfaces and colonization in the Caenorhabditis elegans of representative isolates in the Group A were not affected by high levels of glucose. However, the biofilm and colonization in the worm of clinical isolates in the Group B were much reduced by high levels of glucose. After quantification by real time RT-PCR, 76% of Group A but just 10% of Group B showed high amount of etcA mRNA. In summary, our results suggested that for most of K. pneumoniae clinical isolates, the amount of etcABC mRNA was positively related to their type 3 fimbriae production in a high level of glucose, thereby to their biofilm formation and colonization in the worm.

Identification of an S-adenosylmethionine (SAM) dependent arsenic methyltransferase in Danio rerio.

Arsenic methylation is an important cellular metabolic process that modulates arsenic toxicity and carcinogenicity. Biomethylation of arsenic produces a series of mono-, di- and tri-methylated arsenic metabolites that can be detected in tissues and excretions. Here we report that zebrafish exposed to arsenite (As(III)) produces organic arsenicals, including MMA(III), MMA(V) and DMA(V) with characteristic tissue ratios, demonstrating that an arsenic methylation pathway exists in zebrafish. In mammals, cellular inorganic arsenic is methylated by a SAM-dependent arsenic methyltransferase, AS3MT. A zebrafish arsenic methyltransferase homolog, As3mt, was identified by sequence alignment. Western blotting analysis showed that As3mt was universally expressed in zebrafish tissues. Prominent expression in liver and intestine correlated with methylated arsenic metabolites detected in those tissues. As3mt was expressed in and purified from Escherichia coli for in vitro functional studies. Our results demonstrated that As3mt methylated As(III) to DMA(V) as an end product and produced MMA(III) and MMA(V) as intermediates. The activity of As3mt was inhibited by elevated concentrations of the substrate As(III) as well as the metalloid selenite, which is a well-known antagonistic micronutrient of arsenic toxicity. The activity As3mt was abolished by substitution of either Cys160 or Cys210, which corresponds to conserved cysteine residues in AS3MT homologs, suggesting that they are involved in catalysis. Expression in zebrafish of an enzyme that has a similar function to human and rodent orthologs in catalyzing intracellular arsenic biomethylation validates the applicability of zebrafish as a valuable vertebrate model for understanding arsenic-associated diseases in humans.

Pathways of arsenic uptake and efflux.

Arsenic is the most prevalent environmental toxic substance and ranks first on the U.S. Environmental Protection Agency's Superfund List. Arsenic is a carcinogen and a causative agent of numerous human diseases. Paradoxically arsenic is used as a chemotherapeutic agent for treatment of acute promyelocytic leukemia. Inorganic arsenic has two biological important oxidation states: As(V) (arsenate) and As(III) (arsenite). Arsenic uptake is adventitious because the arsenate and arsenite are chemically similar to required nutrients. Arsenate resembles phosphate and is a competitive inhibitor of many phosphate-utilizing enzymes. Arsenate is taken up by phosphate transport systems. In contrast, at physiological pH, the form of arsenite is As(OH)(3), which resembles organic molecules such as glycerol. Consequently, arsenite is taken into cells by aquaglyceroporin channels. Arsenic efflux systems are found in nearly every organism and evolved to rid cells of this toxic metalloid. These efflux systems include members of the multidrug resistance protein family and the bacterial exchangers Acr3 and ArsB. ArsB can also be a subunit of the ArsAB As(III)-translocating ATPase, an ATP-driven efflux pump. The ArsD metallochaperone binds cytosolic As(III) and transfers it to the ArsA subunit of the efflux pump. Knowledge of the pathways and transporters for arsenic uptake and efflux is essential for understanding its toxicity and carcinogenicity and for rational design of cancer chemotherapeutic drugs.

A protein containing the DUF1471 domain regulates biofilm formation and capsule production in Klebsiella pneumoniae.

BACKGROUND/PURPOSE: Biofilms formed by Klebsiella pneumoniae on medical devices increase infection risk. Fimbriae and capsule polysaccharides (CPSs) are important factors involved in biofilm formation. KP1_4563 in K. pneumoniae NTUH-K2044, a small protein containing the DUF1471 domain, was reported to inhibit type 3 fimbriae function. In this study, we aimed to determine whether the KP1_4563 homolog is conserved in each K. pneumoniae isolate and what role it has in Klebsiella biofilms. METHODS: The genomes of K. pneumoniae NTUH-K2044, CG43, MGH78578, KPPR1 and STU1 were compared. The KP1_4563 homolog in K. pneumoniae STU1 was named orfX. Biofilms of wild-type and orfX mutant strains from K. pneumoniae STU1 and one clinical isolate, 83535, were quantified. Transcription levels of the type 3 fimbrial genes, mrkA and mrkH, were investigated by RT-qPCR. MrkA of the wild-type and orfX mutant were observed by Western blotting. The morphology of bacterial cells was observed by transmission electron microscopy (TEM). Bacterial CPSs were quantified. RESULTS: The gene and upstream region of orfX were conserved among the five K. pneumoniae isolates. Deletion of orfX enhanced Klebsiella biofilm formation. However, the amount of mRNA from mrkA and mrkH and the level of MrkA protein were not different between the wild type and orfX mutant. In contrast, the amount of CPS in orfX mutants was increased, compared to their parental strains, STU1 and 83535. CONCLUSION: The role of orfX is speculated to be conserved in most K. pneumoniae isolates. OrfX negatively controlled biofilm formation by reducing CPS, not type 3 fimbriae, production.

G6PD: A hub for metabolic reprogramming and redox signaling in cancer.

Metabolic hubs play a major role in the initiation and development of cancer. Oncogenic signaling pathways drive metabolic reprogramming and alter redox homeostasis. G6PD has potential oncogenic activity and it plays a pivotal role in cell proliferation, survival and stress responses. Aberrant activation of G6PD via metabolic reprogramming alters NADPH levels, leading to an antioxidant or a pro-oxidant environment which can either enhance DNA oxidative damage and genomic instability or initiate oncogenic signaling. Nutrient deprivation can rewire metabolism, which leads to mutations that determine a cancer cell's fate. Deregulated G6PD status and oxidative stress form a vicious cycle, which paves the way for cancer progression. This review aims to update and focus the potential role of G6PD in metabolic reprogramming and redox signaling in cancer.

G6PD deficiency, redox homeostasis, and viral infections: implications for SARS-CoV-2 (COVID-19).

The COVID-19 pandemic has so far affected more than 45 million people and has caused over 1 million deaths worldwide. Infection with SARS-CoV-2, the pathogenic agent, which is associated with an imbalanced redox status, causes hyperinflammation and a cytokine storm, leading to cell death. Glucose-6-phosphate dehydrogenase (G6PD) deficient individuals may experience a hemolytic crisis after being exposed to oxidants or infection. Individuals with G6PD deficiency are more susceptible to coronavirus infection than individuals with normally functioning G6PD. An altered immune response to viral infections is found in individuals with G6PD deficiency. Evidence indicates that G6PD deficiency is a predisposing factor of COVID-19.

The PTS Components in Klebsiella pneumoniae Affect Bacterial Capsular Polysaccharide Production and Macrophage Phagocytosis Resistance.

Capsular polysaccharide (CPS) is a crucial virulence factor for Klebsiella pneumoniae infection. We demonstrated an association of CPS production with two phosphoenolpyruvate:carbohydrate phosphotransferase systems (PTSs). Deficiency of crr, encoding enzyme IIA of PTS, in K. pneumoniae enhanced the transcriptional activities of galF, wzi and gnd, which are in the cps gene cluster, leading to high CPS production. A crr mutant exhibited a higher survival rate in 1% hydrogen peroxide than the wild-type. The crr mutant showed less sensitivity to engulfment by macrophage (RAW 264.7) than the wild-type by observing the intracellular bacteria using confocal laser scanning microscopy (CLSM) and by calculating the colony-forming units (CFU) of intracellular bacteria. After long-term incubation, the survival rate of the intracellular crr mutant was higher than that of the wild-type. Deficiency of crr enhanced the transcriptional activities of etcABC which encodes another putative enzyme II complex of a PTS. Deletion of etcABC in the crr mutant reduced CPS production and the transcriptional activities of galF compared to those of the crr mutant. These results indicated that one PTS component, Crr, represses CPS production by repressing another PTS component, EtcABC, in K. pneumoniae. In addition, PTS plays a role in bacterial resistance to macrophage phagocytosis.

Plant and fungal products that extend lifespan in Caenorhabditis elegans.

The nematode Caenorhabditis elegans is a useful model to study aging due to its short lifespan, ease of manipulation, and available genetic tools. Several molecules and extracts derived from plants and fungi extend the lifespan of C. elegans by modulating aging-related pathways that are conserved in more complex organisms. Modulation of aging pathways leads to activation of autophagy, mitochondrial biogenesis and expression of antioxidant and detoxifying enzymes in a manner similar to caloric restriction. Low and moderate concentrations of plant and fungal molecules usually extend lifespan, while high concentrations are detrimental, consistent with a lifespan-modulating mechanism involving hormesis. We review here molecules and extracts derived from plants and fungi that extend the lifespan of C. elegans, and explore the possibility that these natural substances may produce health benefits in humans.

Reflex and habituation behavior of Caenorhabditis elegans assessed by a mechanical vibration system and image analysis.

BACKGROUND: The nematode Caenorhabditis elegans is an emerging invertebrate animal model for investigating neuronal functions in behavioral assays. C. elegans mechanosensation was characterized by the use of a constant mechanical stimulation transmitter followed by quantitative imaging. NEW METHOD: C. elegans reflex and habituation behaviors were characterized by mechanical vibration followed by image analysis. A custom-designed system consists of an aluminum alloy Petri dish holder frame coupled with a mechanical vibration buzzer delivering adjustable pulsed vibration to an agar plate. The basal and evoked movements of C. elegans were recorded by a microscopic digital camera followed by quantitative analysis using microscopic imaging software. RESULTS: Application of the platform in C. elegans was demonstrated with three proof-of-concept experiments: (1) Evaluation of the reflex response stimulated by tapping and mechanical vibration with a mechano-sensation defective mutant. (2) Comparison of the reflex response stimulated by mechanical vibration between wild type and aging mutants. (3) Assessment of the efficacy of the mechanical vibration system on long-term memory for habituation. COMPARISON WITH EXISTING METHODS: Conventional C. elegans mechanosensation techniques depend on stimulation either by manually touching a single animal or tapping the Petri dish followed by scoring via visual observation from the examiner. The mechanical vibration method has greater capacity compared to conventional methods which are labor-intensive, have low throughput and lack quantifiable parameters. CONCLUSIONS: The mechanical vibration system followed by image analysis is a convenient and integrated platform for investigatingC. elegans reflex and habituation in aging and neural behavioral assays.

IDH-1 deficiency induces growth defects and metabolic alterations in GSPD-1-deficient Caenorhabditis elegans.

NADPH is a reducing equivalent that maintains redox homeostasis and supports reductive biosynthesis. Lack of major NADPH-producing enzymes predisposes cells to growth retardation and demise. It was hypothesized that double deficiency of the NADPH-generating enzymes, GSPD-1 (Glucose-6-phosphate 1-dehydrogenase), a functional homolog of human glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway, and IDH-1 (isocitrate dehydrogenase-1) affect growth and development in the nematode, Caenorhabditis elegans (C. elegans). The idh-1;gspd-1(RNAi) double-deficient C. elegans model displayed shrinkage of body size, growth retardation, slowed locomotion, and impaired molting. Global metabolomic analysis was employed to address whether or not metabolic pathways were altered by severe NADPH insufficiency by the idh-1;gspd-1(RNAi) double-deficiency. The principal component analysis (PCA) points to a distinct metabolomic profile of idh-1;gspd-1(RNAi) double-deficiency. Further metabolomic analysis revealed that NADPH-dependent and glutamate-dependent amino acid biosynthesis were significantly affected. The reduced pool of amino acids may affect protein synthesis, as indicated by the absence of NAS-37 expression during the molting process. In short, double deficiency of GSPD-1 and IDH-1 causes growth retardation and molting defects, which are, in part, attributed to defective protein synthesis, possibly mediated by altered amino acid biosynthesis and metabolism in C. elegans.

The Redox Role of G6PD in Cell Growth, Cell Death, and Cancer.

The generation of reducing equivalent NADPH via glucose-6-phosphate dehydrogenase (G6PD) is critical for the maintenance of redox homeostasis and reductive biosynthesis in cells. NADPH also plays key roles in cellular processes mediated by redox signaling. Insufficient G6PD activity predisposes cells to growth retardation and demise. Severely lacking G6PD impairs embryonic development and delays organismal growth. Altered G6PD activity is associated with pathophysiology, such as autophagy, insulin resistance, infection, inflammation, as well as diabetes and hypertension. Aberrant activation of G6PD leads to enhanced cell proliferation and adaptation in many types of cancers. The present review aims to update the existing knowledge concerning G6PD and emphasizes how G6PD modulates redox signaling and affects cell survival and demise, particularly in diseases such as cancer. Exploiting G6PD as a potential drug target against cancer is also discussed.

Crystal structure of the flavoprotein ArsH from Sinorhizobium meliloti.

Purified ArsH from Sinorhizobium meliloti exhibits NADPH:FMN-dependent reduction of molecular O2 to hydrogen peroxide and catalyzes reduction of azo dyes. The structure of ArsH was determined at 1.8A resolution. ArsH crystallizes with eight molecules in the asymmetric unit forming two tetramers. Each monomer has a core domain with a central five-stranded parallel beta-sheet and two monomers interact to form a classical flavodoxin-like dimer. The N- and C-terminal extensions of ArsH are involved in interactions between subunits and tetramer formation. The structure may provide insight in how ArsH participates in arsenic detoxification.