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L -Ergothioneine (ET), the 2-thioimidazole derivative of trimethylhistidine, is biosynthesized by select fungi and bacteria, notably Mycobacterium tuberculosis , and functions as a scavenger of reactive oxygen species. The extent to which ET broadly functions in bacterial cells unable to synthesize it is unknown. Here we show that spd _1642-1643 in Streptococcus pneumoniae , a Gram-positive respiratory pathogen, encodes an ET uptake ATP-binding cassette (ABC) transporter, designated EgtU. The solute binding domain (SBD) of EgtU, EgtUC, binds ET with high affinity and exquisite specificity in a cleft between the two subdomains, with cation-π interactions engaging the betaine moiety and a network of water molecules that surround the thioimidazole ring. EgtU is highly conserved among known quaternary amine compound-specific transporters and widely distributed in Firmicutes, including the human pathogens Listeria monocytogenes , as BilEB, Enterococcus faecalis and Staphylococcus aureus . ET increases the chemical diversity of the low molecular weight thiol pool in Gram-positive human pathogens and may contribute to antioxidant defenses in the infected host. The extent to which human bacterial pathogens broadly utilize ergothioneine as an antioxidant is unknown. Here, authors describe the discovery of a specific transporter for ergothioneine in a respiratory pathogen that is highly conserved among Firmicutes.

Cysteine thiol-based transcriptional regulators orchestrate the coordinated regulation of redox homeostasis and other cellular processes by ‘sensing’ or detecting a specific redox-active molecule, which in turn activates the transcription of a specific detoxification pathway. The extent to which these sensors are truly specific in cells for a singular class of reactive small-molecule stressors, for example, reactive oxygen or sulfur species, is largely unknown. Here, we report structural and mechanistic insights into the thiol-based transcriptional repressor SqrR, which reacts exclusively with oxidized sulfur species such as persulfides, to yield a tetrasulfide bridge that inhibits DNA operator–promoter binding. Evaluation of crystallographic structures of SqrR in various derivatized states, coupled with the results of a mass spectrometry-based kinetic profiling strategy, suggest that persulfide selectivity is determined by structural frustration of the disulfide form. These findings led to the identification of an uncharacterized repressor from the bacterial pathogen Acinetobacter baumannii as a persulfide sensor. Structural and kinetic analyses of the transcriptional repressor SqrR in multiple states indicate that its persulfide selectivity is determined by structural frustration in the disulfide form, favoring formation of the tetrasulfide-bridged product.

Although hydrogen sulfide (H 2 S) has long been known as a respiratory poison, recent reports in numerous bacterial pathogens reveal that H 2 S and more downstream oxidized forms of sulfur collectedly termed reactive sulfur species (RSS) function as antioxidants to combat host efforts to clear the infection. Here, we present a comprehensive analysis of the transcriptional and proteomic response of A. baumannii to exogenous sulfide as a model for how this important human pathogen manages sulfide/RSS homeostasis. We show that A. baumannii is unique in that it encodes two independent persulfide sensing and detoxification pathways that govern the speciation of bioactive sulfur in cells. The secondary persulfide sensor, BigR, impacts the expression of biofilm-associated genes; in addition, we identify two other transcriptional regulators known or projected to regulate biofilm formation, BfmR and Crp, as highly persulfidated in sulfide-exposed cells. These findings significantly strengthen the connection between sulfide homeostasis and biofilm formation in an important human pathogen. Acinetobacter baumannii is an opportunistic nosocomial pathogen that is the causative agent of several serious infections in humans, including pneumonia, sepsis, and wound and burn infections. A. baumannii is also capable of forming proteinaceous biofilms on both abiotic and epithelial cell surfaces. Here, we investigate the response of A. baumannii toward sodium sulfide (Na 2 S), known to be associated with some biofilms at oxic/anoxic interfaces. The addition of exogenous inorganic sulfide reveals that A. baumannii encodes two persulfide-sensing transcriptional regulators, a primary σ 54 -dependent transcriptional activator (FisR), and a secondary system controlled by the persulfide-sensing biofilm growth-associated repressor (BigR), which is only induced by sulfide in a fisR deletion strain. FisR activates an operon encoding a sulfide oxidation/detoxification system similar to that characterized previously in Staphylococcus aureus , while BigR regulates a secondary persulfide dioxygenase (PDO2) as part of yeeE-yedE-pdo2 sulfur detoxification operon, found previously in Serratia spp. Global S- sulfuration (persulfidation) mapping of the soluble proteome reveals 513 persulfidation targets well beyond FisR-regulated genes and includes five transcriptional regulators, most notably the master biofilm regulator BfmR and a poorly characterized catabolite regulatory protein (Crp). Both BfmR and Crp are well known to impact biofilm formation in A. baumannii and other organisms, respectively, suggesting that persulfidation of these regulators may control their activities. The implications of these findings on bacterial sulfide homeostasis, persulfide signaling, and biofilm formation are discussed. IMPORTANCE Although hydrogen sulfide (H 2 S) has long been known as a respiratory poison, recent reports in numerous bacterial pathogens reveal that H 2 S and more downstream oxidized forms of sulfur collectedly termed reactive sulfur species (RSS) function as antioxidants to combat host efforts to clear the infection. Here, we present a comprehensive analysis of the transcriptional and proteomic response of A. baumannii to exogenous sulfide as a model for how this important human pathogen manages sulfide/RSS homeostasis. We show that A. baumannii is unique in that it encodes two independent persulfide sensing and detoxification pathways that govern the speciation of bioactive sulfur in cells. The secondary persulfide sensor, BigR, impacts the expression of biofilm-associated genes; in addition, we identify two other transcriptional regulators known or projected to regulate biofilm formation, BfmR and Crp, as highly persulfidated in sulfide-exposed cells. These findings significantly strengthen the connection between sulfide homeostasis and biofilm formation in an important human pathogen.

Manhattan, Berlin and New Delhi all need to take action to adapt to climate change and to reduce greenhouse gas emissions. While case studies on these cities provide valuable insights, comparability and scalability remain sidelined. It is therefore timely to review the state-of-the-art in data infrastructures, including earth observations, social media data, and how they could be better integrated to advance climate change science in cities and urban areas. We present three routes for expanding knowledge on global urban areas: mainstreaming data collections, amplifying the use of big data and taking further advantage of computational methods to analyse qualitative data to gain new insights. These data-based approaches have the potential to upscale urban climate solutions and effect change at the global scale. Cities have an increasingly integral role in addressing climate change. To gain a common understanding of solutions, we require adequate and representative data of urban areas, including data on related greenhouse gas emissions, climate threats and of socio-economic contexts. Here, we review the current state of urban data science in the context of climate change, investigating the contribution of urban metabolism studies, remote sensing, big data approaches, urban economics, urban climate and weather studies. We outline three routes for upscaling urban data science for global climate solutions: 1) Mainstreaming and harmonizing data collection in cities worldwide; 2) Exploiting big data and machine learning to scale solutions while maintaining privacy; 3) Applying computational techniques and data science methods to analyse published qualitative information for the systematization and understanding of first-order climate effects and solutions. Collaborative efforts towards a joint data platform and integrated urban services would provide the quantitative foundations of the emerging global urban sustainability science.

Hydrogen sulfide (H2S) is implicated as a cytoprotective agent that bacteria employ in response to host-induced stressors, such as oxidative stress and antibiotics. The physiological benefits often attributed to H2S, however, are likely a result of downstream, more oxidized forms of sulfur, collectively termed reactive sulfur species (RSS) and including the organic persulfide (RSSH). Here, we investigated the metabolic response of the commensal gut microorganism Enterococcus faecalis to exogenous Na2S as a proxy for H2S/RSS toxicity. We found that exogenous sulfide increases protein abundance for enzymes responsible for the biosynthesis of coenzyme A (CoA). Proteome S-sulfuration (persulfidation), a posttranslational modification implicated in H2S signal transduction, is also widespread in this organism and is significantly elevated by exogenous sulfide in CstR, the RSS sensor, coenzyme A persulfide (CoASSH) reductase (CoAPR) and enzymes associated with de novo fatty acid biosynthesis and acetyl-CoA synthesis. Exogenous sulfide significantly impacts the speciation of fatty acids as well as cellular concentrations of acetyl-CoA, suggesting that protein persulfidation may impact flux through these pathways. Indeed, CoASSH is an inhibitor of E. faecalis phosphotransacetylase (Pta), suggesting that an important metabolic consequence of increased levels of H2S/RSS may be over-persulfidation of this key metabolite, which, in turn, inhibits CoA and acyl-CoA-utilizing enzymes. Our 2.05 Å crystallographic structure of CoA-bound CoAPR provides new structural insights into CoASSH clearance in E. faecalis.

Globally consistent measurements of airborne metal concentrations in fine particulate matter (PM 2.5 ) are important for understanding potential health impacts, prioritizing air pollution mitigation strategies, and enabling global chemical transport model development. PM 2.5 filter samples (N ~ 800 from 19 locations) collected from a globally distributed surface particulate matter sampling network (SPARTAN) between January 2013 and April 2019 were analyzed for particulate mass and trace metals content. Metal concentrations exhibited pronounced spatial variation, primarily driven by anthropogenic activities. PM 2.5 levels of lead, arsenic, chromium, and zinc were significantly enriched at some locations by factors of 100–3000 compared to crustal concentrations. Levels of metals in PM 2.5 and PM 10 exceeded health guidelines at multiple sites. For example, Dhaka and Kanpur sites exceeded the US National Ambient Air 3-month Quality Standard for lead (150 ng m −3 ). Kanpur, Hanoi, Beijing and Dhaka sites had annual mean arsenic concentrations that approached or exceeded the World Health Organization’s risk level for arsenic (6.6 ng m −3 ). The high concentrations of several potentially harmful metals in densely populated cites worldwide motivates expanded measurements and analyses.

Cities have become increasingly recognized as key sites for climate research and action. Recently, these efforts have been significantly advanced through science-policy-practice partnerships. The objective of this paper is to assess how these partnerships are structured, the research and action agenda that underpins them, and how this agenda is being articulated and implemented. The assessment also helps to define some of the conceptual and operational gaps faced by the science-policy-practice community and how they can be addressed. The work evaluates the critical conditions for promoting these advances including the definition and fulfillment of knowledge needs, the integration of different perspectives and approaches, establishment of pathways to finance the urban climate research and action community, and creation and promotion of new partnerships. The paper concludes with a series of strategies and recommendations for how targeted policy adjustments can accelerate and support the production of actionable knowledge and this integrated researcher-policymaker-practitioner community.

Aerosol particles are an important part of the Earth climate system, and their concentrations are spatially and temporally heterogeneous, as well as being variable in size and composition. Particles can interact with incoming solar radiation and outgoing longwave radiation, change cloud properties, affect photochemistry, impact surface air quality, change the albedo of snow and ice, and modulate carbon dioxide uptake by the land and ocean. High particulate matter concentrations at the surface represent an important public health hazard. There are substantial data sets describing aerosol particles in the literature or in public health databases, but they have not been compiled for easy use by the climate and air quality modeling community. Here, we present a new compilation of PM2.5 and PM10 surface observations, including measurements of aerosol composition, focusing on the spatial variability across different observational stations. Climate modelers are constantly looking for multiple independent lines of evidence to verify their models, and in situ surface concentration measurements, taken at the level of human settlement, present a valuable source of information about aerosols and their human impacts complementarily to the column averages or integrals often retrieved from satellites. We demonstrate a method for comparing the data sets to outputs from global climate models that are the basis for projections of future climate and large-scale aerosol transport patterns that influence local air quality. Annual trends and seasonal cycles are discussed briefly and are included in the compilation. Overall, most of the planet or even the land fraction does not have sufficient observations of surface concentrations – and, especially, particle composition – to characterize and understand the current distribution of particles. Climate models without ammonium nitrate aerosols omit ∼ 10 % of the globally averaged surface concentration of aerosol particles in both PM2.5 and PM10 size fractions, with up to 50 % of the surface concentrations not being included in some regions. In these regions, climate model aerosol forcing projections are likely to be incorrect as they do not include important trends in short-lived climate forcers.

Hydrogen sulfide (H2S) is implicated as a cytoprotective agent that bacteria utilize in response to host-induced stressors such as oxidative stress and antibiotics. The physiological benefits often attributed to H2S however, are likely a result of downstream, more oxidized forms of sulfur collectively termed reactive sulfur species (RSS). RSS include the organic persulfide (RSSH), which is thought to react with reactive oxygen species at sites of infection while also inactivating -lactam antibiotics. While our understanding of H2S/RSS at the host-pathogen interface continues to improve, comparatively little is known about the mechanisms by which bacteria maintain sulfide/RSS homeostasis and what cellular processes are negatively impacted by H2S/RSS toxicity. Here, we investigate sulfide homeostasis in two major human pathogens associated with nosocomial infections, the commensal Enterococcus faecalis (E. faecalis) and Acinetobacter baumannii (A. baumannii), as well as their physiological response to exogenous sulfide. We find that E. faecalis and A. baumannii encode for remarkably distinct RSS-sensing transcriptional regulators that regulate genes that encode enzymes that are known or projected to be involved in the biogenesis of RSS from H2S and subsequent clearance of RSS from cells. These bacteria harbor significant levels of RSS as low molecular weight (LMW) persulfides, including coenzyme A persulfide (CoASSH), which are perturbed by exogenously added disodium sulfide. We find that proteome S-sulfuration (persulfidation), a posttranslational modification (PTM) implicated in H2S signaling, is widespread in these organisms. In E. faecalis, proteome persulfidation is significantly increased by exogenous sulfide in enzymes associated with fatty acid and acetyl-CoA biosynthesis. In addition, we find that exogenous sulfide significantly impacts the speciation of fatty acids as well as cellular concentrations of acetyl-CoA suggesting protein persulfidation may impact flux through these pathways. Lastly, we show that CoASSH is a potent inhibitor of E. faecalis phosphotransacetylase suggesting that a major metabolic consequence of increased levels of H2S/RSS is over-persulfidation of this key metabolite. In summary, this work expands our understanding of the molecular mechanisms that maintain H2S/RSS homeostasis and the physiological impact of exogenous sulfide in two major human pathogens, while highlighting the therapeutic potential of targeting sulfide homeostasis systems in bacterial infections.

Hydrogen sulfide (H[sub.2]S) is implicated as a cytoprotective agent that bacteria employ in response to host-induced stressors, such as oxidative stress and antibiotics. The physiological benefits often attributed to H[sub.2]S, however, are likely a result of downstream, more oxidized forms of sulfur, collectively termed reactive sulfur species (RSS) and including the organic persulfide (RSSH). Here, we investigated the metabolic response of the commensal gut microorganism Enterococcus faecalis to exogenous Na[sub.2]S as a proxy for H[sub.2]S/RSS toxicity. We found that exogenous sulfide increases protein abundance for enzymes responsible for the biosynthesis of coenzyme A (CoA). Proteome S-sulfuration (persulfidation), a posttranslational modification implicated in H[sub.2]S signal transduction, is also widespread in this organism and is significantly elevated by exogenous sulfide in CstR, the RSS sensor, coenzyme A persulfide (CoASSH) reductase (CoAPR) and enzymes associated with de novo fatty acid biosynthesis and acetyl-CoA synthesis. Exogenous sulfide significantly impacts the speciation of fatty acids as well as cellular concentrations of acetyl-CoA, suggesting that protein persulfidation may impact flux through these pathways. Indeed, CoASSH is an inhibitor of E. faecalis phosphotransacetylase (Pta), suggesting that an important metabolic consequence of increased levels of H[sub.2]S/RSS may be over-persulfidation of this key metabolite, which, in turn, inhibits CoA and acyl-CoA-utilizing enzymes. Our 2.05 Å crystallographic structure of CoA-bound CoAPR provides new structural insights into CoASSH clearance in E. faecalis.