Bacterial Hydrogen Sulfide Research Articles

Multimodal nanoimmunotherapy engages neutrophils to eliminate Staphylococcus aureus infections.

The increasing prevalence of antimicrobial resistance in Staphylococcus aureus necessitates alternative therapeutic approaches. Neutrophils play a crucial role in the fight against S. aureus but suffer from deficiencies in function leading to increased infection. Here we report a nanoparticle-mediated immunotherapy aimed at potentiating neutrophils to eliminate S. aureus. The nanoparticles consist of naftifine, haemoglobin (Hb) and a red blood cell membrane coating. Naftifine disrupts staphyloxanthin biosynthesis, Hb reduces bacterial hydrogen sulfide levels and the red blood cell membrane modifies bacterial lipid composition. Collectively, the nanoparticles can sensitize S. aureus to host oxidant killing. Furthermore, in the infectious microenvironment, Hb triggers lipid peroxidation in S. aureus, promoting neutrophil chemotaxis. Oxygen supplied by Hb can also significantly enhance the bactericidal capability of the recruited neutrophils by restoring neutrophil respiratory burst via hypoxia relief. This multimodal nanoimmunotherapy demonstrates excellent therapeutic efficacy in treating antimicrobial-resistant S. aureus persisters, biofilms and S. aureus-induced infection in mice.

Geochemical transformations of sulfur and their role in the formation of different types and subtypes of saline lakes in Southeastern Transbaikalia

This study focused on the chemistry and isotopes of sulfur in lakes. The bottom sediments and water columns of lakes were found to contain reduced forms of sulfur, including hydrogen sulfide ions, elemental sulfur, and thiosulfate ions, along with sulfate ions. It was determined that elemental sulfur in lakes is present mainly in the form of suspensions and colloids, and the proportion of elemental sulfur in polysulfides increases with increasing water pH. It was shown that sulfate reduction results in the greatest isotope fractionation, with a light sulfur isotope accumulating in hydrogen sulfide ions and a heavy sulfur isotope accumulating in sulfate ions. It was confirmed that the abiotic reaction of hydrogen sulfide with oxygen yields a mixture of products that are depleted in 34S and enriched in 34S in hydrogen sulfide. In contrast, the microbial oxidation of HS− → S0 yields zerovalent sulfur, which is 2–4‰ heavier than the initial product. It was shown that the loss of sulfate ions due to bacterial reduction is most significant in subtype-I and subtype-III chloride and soda lakes. In contrast, in subtype-II sulfate and soda lakes, an increase in sulfate ions was noted due to the oxidation of hydrogen sulfides in water-bearing rocks and bacterial hydrogen sulfide. This finding indicated that in addition to evaporation, the formation of a particular type and subtype of saline lake involves the processes of aluminosilicate hydrolysis, sulfate reduction and hydrogen sulfide oxidation.

First clinical evidence that trimethylsulfonium can serve as a biomarker for the production of the signaling molecule hydrogen sulfide

BackgroundHydrogen sulfide (H2S) is established as the third gaseous signaling molecule and is known to be overproduced in down syndrome (DS) due to the extra copy of the CBS gene on chromosome 21, which has been suggested to contribute to the clinical manifestation of this condition. We recently discovered trimethylsulfonium (TMS) in human urine and highlighted its potential as a selective methylation metabolite of endogenously produced H2S, but the clinical utility of this novel metabolite has not been previously investigated. We hypothesize that the elevation of H2S production in DS would be reflected by an elevation in the methylation product TMS. MethodsTo test this hypothesis, a case-control study was performed and the urinary levels of TMS were found to be higher in the DS group (geo. mean 4.5 nM, 95 % CI 2.4–3.9) than in the control (N) group (3.1 nM, 3.5–6.0), p-value 0.01, whereas the commonly used biomarker of hydrogen sulfide, thiosulfate, failed to reflect this alteration in H2S production (15 µM (N) vs. 13 µM (DS), p-value 0.24. ResultsThe observed association is in line with the proposed hypothesis and provides first clinical evidence of the utility of TMS as a novel and more sensitive biomarker for the endogenous production of the third gaseous signaling molecule than the conventionally used biomarker thiosulfate, which is heavily dependent on bacterial hydrogen sulfide production. ConclusionThis work shows that TMS must be explored in clinical conditions where altered metabolism of hydrogen sulfide is implicated.

Microbial metabolites are involved in tumorigenesis and development by regulating immune responses.

The human microbiota is symbiotic with the host and can create a variety of metabolites. Under normal conditions, microbial metabolites can regulate host immune function and eliminate abnormal cells in a timely manner. However, when metabolite production is abnormal, the host immune system might be unable to identify and get rid of tumor cells at the early stage of carcinogenesis, which results in tumor development. The mechanisms by which intestinal microbial metabolites, including short-chain fatty acids (SCFAs), microbial tryptophan catabolites (MTCs), polyamines (PAs), hydrogen sulfide, and secondary bile acids, are involved in tumorigenesis and development by regulating immune responses are summarized in this review. SCFAs and MTCs can prevent cancer by altering the expression of enzymes and epigenetic modifications in both immune cells and intestinal epithelial cells. MTCs can also stimulate immune cell receptors to inhibit the growth and metastasis of the host cancer. SCFAs, MTCs, bacterial hydrogen sulfide and secondary bile acids can control mucosal immunity to influence the occurrence and growth of tumors. Additionally, SCFAs, MTCs, PAs and bacterial hydrogen sulfide can also affect the anti-tumor immune response in tumor therapy by regulating the function of immune cells. Microbial metabolites have a good application prospect in the clinical diagnosis and treatment of tumors, and our review provides a good basis for related research.

Bacterial hydrogen sulfide drives cryptic redox chemistry in gut microbial communities.

Microbial biochemistry contributes to a dynamic environment in the gut. Yet, how bacterial metabolites such as hydrogen sulfide (H2S) mechanistically alter the gut chemical landscape is poorly understood. Here we show that microbially generated H2S drives the abiotic reduction of azo (R-N = N-R') xenobiotics, which are commonly found in Western food dyes and drugs. This nonenzymatic reduction of azo compounds is demonstrated in Escherichia coli cultures, in human faecal microbial communities and in vivo in male mice. Changing dietary levels of the H2S xenobiotic redox partner Red 40 transiently decreases mouse faecal sulfide levels, demonstrating that a xenobiotic can attenuate sulfide concentration and alleviate H2S accumulation in vivo. Cryptic H2S redox chemistry thus can modulate sulfur homeostasis, alter the chemical landscape in the gut and contribute to azo food dye and drug metabolism. Interactions between chemicals derived from microbial communities may be a key feature shaping metabolism in the gut.

Obesity induced gut dysbiosis contributes to disease severity in an animal model of multiple sclerosis.

BackgroundMultiple sclerosis (MS) is an inflammatory and demyelinating disease of the CNS. The etiology of MS is complex, and results from the interaction of multiple environmental and genetic factors. Although human leukocyte antigen-HLA alleles such as HLA-DR2 and –DR3 are considered the strongest genetic factors, the environmental factors responsible for disease predisposition are not well understood. Recently, diet and gut microbiota have emerged as an important environmental factors linked to the increased incidence of MS. Especially, western diets rich in protein and fat have been linked to the increased incidence of obesity. Numerous clinical data indicate a role of obesity and gut microbiota in MS; however, the mechanistic link between gut microbiota and obesity in the pathobiology of MS remains unclear. The present study determines the mechanisms driving MS severity in the context of obesity utilizing a high-fat diet (HFD) induced obese HLA-DR3 class-II transgenic mouse model of MS.MethodsHLA-DR3 transgenic mice were kept on a standard HFD diet or Normal Chow (NC) for eight weeks. Gut microbiota composition and functional analysis were performed from the fecal DNA of mice. Experimental autoimmune encephalomyelitis-EAE (an animal model of MS) was induced by immunization with the proteolipid protein-PLP91-110 peptide in complete Freud’s Adjuvant (CFA) and pertussis toxin.ResultsWe observed that HFD-induced obesity caused gut dysbiosis and severe disease compared to mice on NC. Amelioration of disease severity in mice depleted of gut microbiota suggested an important role of gut bacteria in severe EAE in obese mice. Fecal microbiota analysis in HFD mice shows gut microbiota alterations with an increase in the abundance of Proteobacteria and Desulfovibrionaceae bacteria and modulation of various bacterial metabolic pathways including bacterial hydrogen sulfide biosynthetic pathways. Finally, mice on HFD showed increased gut permeability and systemic inflammation suggesting a role gut barrier modulation in obesity induced disease severity.ConclusionsThis study provides evidence for the involvement of the gut microbiome and associated metabolic pathways plus gut permeability in obesity-induced modulation of EAE disease severity. A better understanding of the same will be helpful to identify novel therapeutic targets to reduce disease severity in obese MS patients.

Turning down tolerance

Antimicrobial Drugs Persister cells, which are found in abundance in biofilms, adopt a quiescent state and survive antimicrobial treatments, seeding disease recurrence and incubating new resistance mutations. Building on work implicating the reactive small-molecule hydrogen sulfide in bacterial defense against antibiotics, Shatalin et al. conducted a structure-based screen for inhibitors of a bacterial hydrogen sulfide–producing enzyme and found a group of inhibitors that act through an allosteric mechanism (see the Perspective by Mah). These inhibitors potentiated bactericidal antibiotics in vitro and in mouse infection models. They also suppressed persister bacteria and disrupted biofilm formation. This strategy of taking out persister cells may be promising for treating recalcitrant infections and holding the line against drug-resistant bacteria. Science , abd8377, this issue p. [1169][1]; see also abj3062, p. [1153][2] [1]: /lookup/doi/10.1126/science.abd8377 [2]: /lookup/doi/10.1126/science.abj3062

Inhibitors of bacterial H2S biogenesis targeting antibiotic resistance and tolerance.

Emergent resistance to all clinical antibiotics calls for the next generation of therapeutics. Here we report an effective antimicrobial strategy targeting the bacterial hydrogen sulfide (H2S)-mediated defense system. We identified cystathionine γ-lyase (CSE) as the primary generator of H2S in two major human pathogens, Staphylococcus aureus and Pseudomonas aeruginosa, and discovered small molecules that inhibit bacterial CSE. These inhibitors potentiate bactericidal antibiotics against both pathogens in vitro and in mouse models of infection. CSE inhibitors also suppress bacterial tolerance, disrupting biofilm formation and substantially reducing the number of persister bacteria that survive antibiotic treatment. Our results establish bacterial H2S as a multifunctional defense factor and CSE as a drug target for versatile antibiotic enhancers.

Estimation of bacterial hydrogen sulfide production in vitro

Oral bacterial hydrogen sulfide (H2S) production was estimated comparing two different colorimetric methods in microtiter plate format. High H2S production was seen for Fusobacterium spp., Treponema denticola, and Prevotella tannerae, associated with periodontal disease. The production differed between the methods indicating that H2S production may follow different pathways.

Contemporaneous early diagenetic formation of organic and inorganic sulfur in estuarine sediments from St. Andrew Bay, Florida, USA

Estuarine sediment samples were collected from nine stations in St. Andrew Bay near Panama City, Florida, USA. Contrasting grain size and varying concentration of organic carbon allowed a comparative study of the relationships among organic degradation processes, sulfur cycling, and diagenetic removal of dissolved sulfide produced by bacterial sulfate reduction. Abundance and sulfur isotopic composition were determined for dissolved sulfide, dissolved sulfate, pyrite, humic-acid sulfur, fulvic-acid sulfur, and elemental sulfur. Presence of free dissolved sulfide and enrichment in 34S of porewater sulfate in samples from organic-rich, muddy sediments of St. Andrew Bay indicate high rates of sulfate reduction and anoxic conditions below 5 mm depth. Such conditions are not reflected in samples from organic-poor, sandy, near-shore sediments collected from highly productive areas occupied by seagrass beds. In this estuarine system, pyrite and fulvic-acid sulfur are the largest sinks for sulfide produced by bacterial sulfate reduction. Strong correlation between abundances of pyrite and fulvic-acid sulfur suggests coincident formation in the uppermost 10 cm of sediment. Large differences in isotopic composition between these two species and consistent enrichment in 34S of the fulvic-acid fraction, however, indicate two different reaction pathways. Abundance and sulfur isotopic composition of humic-acid and fulvic-acid sulfur suggest that organic sulfur is derived from mixing between (1) 34S-depleted sulfur with an unknown oxidation state that was recycled from bacterial hydrogen sulfide and (2) 34S-enriched sulfur interpreted as primary biosynthetic sulfur originally assimilated from dissolved sulfate. Samples taken from sandy sediment localities where aquatic vascular plants are rooted in the anoxic zone show a strong depletion in 34S in the fulvic-acid sulfur fraction suggesting recycled hydrogen sulfide as the dominant source of organic sulfur.

歯槽膿漏症と口腔内硫化水素産生菌の関係

A medium which detects H2S produced by bacteria was newly designed by Onisi and Tachibana, being consisted of agar 2%, peptone 2%, meat extract 1%, NaCl 0.2%, sodium thiosulf ate 0.008%, sodium sulfite 0.04%, lead acetate 0.3%, glucose 0.1%, adjusted at pH 6.8. Dental scrapping from 195 apparently healthy tooth surfaces, and from 112 cavities, and pathological exudates from 150 pyorrhea pockets were inoculated in the media in order to find incidence of H2S activity of these three different categories of specimens.The positive reaction was found at 86.7% of pyorrhea specimens, at 66, 9% of cavity deposits and at 60% of healthy scrappings. The differences between pyorrhea and the rest were estimated to be significant.The positive cultures were been plated on the same medium to identify the organisms corresponding to the H2S production there in, i.e., 29 Veillonella, 7 Escherichia, 4 Bacteria, 5 Neisseria, 6 aerobic Micrococci, 2 anaerobic Micrococci, 2 Kurthia, one Corynebacteria and one Diplococcus were resulted, but neither Fusobacteria nor Treponema which may possibly major H2S producers in the pyorrhea pocket. Veillonella, the majority of the genera showing positive reaction, Gram negative rods, the most intensive producers of H2S, Fusobacteria and Treponema would be summarized to be dominant genera of H2S production in the case of pyorrhea alveolaris. As the relation between pyorrhea and bacterial hydrogen sulfide, it is considered that the reducing action of the latter may affect the keratin layer of the gingival epithelium to create the S-S linkage in it.