Clinical Decision Support System for Guidelines-Based Treatment of Gonococcal Infections, Screening for HIV, and Prescription of Pre-Exposure Prophylaxis: Design and Implementation Study.

BACKGROUND: The syndemic nature of gonococcal infections and HIV provides an opportunity to develop a synergistic intervention tool that could address the need for adequate treatment for gonorrhea, screen for HIV infections, and offer pre-exposure prophylaxis (PrEP) for persons who meet the criteria. By leveraging information available on electronic health records, a clinical decision support (CDS) system tool could fulfill this need and improve adherence to Centers for Disease Control and Prevention (CDC) treatment and screening guidelines for gonorrhea, HIV, and PrEP. OBJECTIVE: The goal of this study was to translate portions of CDC treatment guidelines for gonorrhea and relevant portions of HIV screening and prescribing PrEP that stem from a diagnosis of gonorrhea as an electronic health record-based CDS intervention. We also assessed whether this CDS solution worked in real-world clinic. METHODS: We developed 4 tools for this CDS intervention: a form for capturing sexual history information (SmartForm), rule-based alerts (best practice advisory), an enhanced sexually transmitted infection (STI) order set (SmartSet), and a documentation template (SmartText). A mixed methods pre-post design was used to measure the feasibility, use, and usability of the CDS solution. The study period was 12 weeks with a baseline patient sample of 12 weeks immediately prior to the intervention period for comparison. While the entire clinic had access to the CDS solution, we focused on a subset of clinicians who frequently engage in the screening and treatment of STIs within the clinical site under the name "X-Clinic." We measured the use of the CDS solution within the population of patients who had either a confirmed gonococcal infection or an STI-related chief complaint. We conducted 4 midpoint surveys and 3 key informant interviews to quantify perception and impact of the CDS solution and solicit suggestions for potential future enhancements. The findings from qualitative data were determined using a combination of explorative and comparative analysis. Statistical analysis was conducted to compare the differences between patient populations in the baseline and intervention periods. RESULTS: Within the X-Clinic, the CDS alerted clinicians (as a best practice advisory) in one-tenth (348/3451, 10.08%) of clinical encounters. These 348 encounters represented 300 patients; SmartForms were opened for half of these patients (157/300, 52.33%) and was completed for most for them (147/300, 89.81%). STI test orders (SmartSet) were initiated by clinical providers in half of those patients (162/300, 54%). HIV screening was performed during about half of those patient encounters (191/348, 54.89%). CONCLUSIONS: We successfully built and implemented multiple CDC treatment and screening guidelines into a single cohesive CDS solution. The CDS solution was integrated into the clinical workflow and had a high rate of use.

A unique subseafloor microbiosphere in the Mariana Trench driven by episodic sedimentation.

Hadal trenches are characterized by enhanced and infrequent high-rate episodic sedimentation events that likely introduce not only labile organic carbon and key nutrients but also new microbes that significantly alter the subseafloor microbiosphere. Currently, the role of high-rate episodic sedimentation in controlling the composition of the hadal subseafloor microbiosphere is unknown. Here, analyses of carbon isotope composition in a ~ 750 cm long sediment core from the Challenger Deep revealed noncontinuous deposition, with anomalous 14C ages likely caused by seismically driven mass transport and the funneling effect of trench geomorphology. Microbial community composition and diverse enzyme activities in the upper ~ 27 cm differed from those at lower depths, probably due to sudden sediment deposition and differences in redox condition and organic matter availability. At lower depths, microbial population numbers, and composition remained relatively constant, except at some discrete depths with altered enzyme activity and microbial phyla abundance, possibly due to additional sudden sedimentation events of different magnitude. Evidence is provided of a unique role for high-rate episodic sedimentation events in controlling the subsurface microbiosphere in Earth's deepest ocean floor and highlight the need to perform thorough analysis over a large depth range to characterize hadal benthic populations. Such depositional processes are likely crucial in shaping deep-water geochemical environments and thereby the deep subseafloor biosphere. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00212-y.

The production of dimethylsulfoniopropionate by bacteria with mmtN linked to non-ribosomal peptide synthase gene.

Dimethylsulfoniopropionate (DMSP) is a vital sulfur-containing compound with worldwide significance, serving as the primary precursor for dimethyl sulfide (DMS), a volatile sulfur compound that plays a role in atmospheric chemistry and influences the Earth's climate on a global scale. The study investigated the ability of four bacterial strains, namely Acidimangrovimonas sediminis MS2-2 (MS2-2), Hartmannibacter diazotrophicus E18T (E18T), Rhizobium lusitanum 22705 (22705), and Nitrospirillum iridis DSM22198 (DSM22198), to produce and degrade DMSP. These strains were assessed for their DMSP synthesis ability with the mmtN linked to non-ribosomal peptide synthase (NRPS) gene. The results showed that MS2-2, and E18T bacteria, which contained the mmtN but not linked to an NRPS gene, increased DMSP production with increasing salinity. The highest production of DMSP was achieved at 25 PSU when either methionine was added or low nitrogen conditions were present, yielding 1656.03 ± 41.04 and 265.59 ± 9.17 nmol/mg protein, respectively, and subsequently under the conditions of methionine addition or low nitrogen, both strains reached their maximum DMSP production at 25 PSU. Furthermore, the strains MS2-2, E18T, and 22705 with the mmtN gene but not linked to an NRPS gene were found to be involved in DMS production. This research contributes to the understanding of the genes involved in DMSP biosynthesis in bacteria that produce DMSP.

Using Electronic Health Record Data to Measure the Latent Tuberculosis Infection Care Cascade in Safety-Net Primary Care Clinics.

Introduction: Prevention of tuberculosis disease through diagnosis and treatment of latent tuberculosis infection is critical for achieving tuberculosis elimination in the U.S. Diagnosis and treatment of latent tuberculosis infection in safety-net primary care settings that serve patients at risk for tuberculosis may increase uptake of this prevention effort and accelerate progress toward elimination. Optimizing tuberculosis prevention in these settings requires measuring the latent tuberculosis infection care cascade (testing, diagnosis, and treatment) and identifying gaps to develop solutions to overcome barriers. We used electronic health record data to describe the latent tuberculosis infection care cascade and identify gaps among a network of safety-net primary care clinics. Methods: Electronic health record data for patients seen in the OCHIN Clinical Network, the largest network of safety-net clinics in the U.S., between 2012 and 2019 were extracted. electronic health record data were used to measure the latent tuberculosis infection care cascade: patients who met tuberculosis screening criteria on the basis of current recommendations were tested for tuberculosis infection, diagnosed with latent tuberculosis infection, and prescribed treatment for latent tuberculosis infection. Outcomes were stratified by diagnostic test and treatment regimen. Results: Among 1.9 million patients in the analytic cohort, 43.5% met tuberculosis screening criteria, but only 21.4% were tested for latent tuberculosis infection; less than half (40.4%) were tested using an interferon-gamma release assay. Among those with a valid result, 10.5% were diagnosed with latent tuberculosis infection, 29.1% of those were prescribed latent tuberculosis infection treatment, and only 33.6% were prescribed a recommended rifamycin-based regimen. Conclusions: Electronic health record data can be used to measure the latent tuberculosis infection care cascade. A large proportion of patients in this safety-net clinical network are at high risk for tuberculosis infection. Addressing identified gaps in latent tuberculosis infection testing and treatment may have a direct impact on improving tuberculosis prevention in primary care clinics and accelerate progress toward elimination.

SAR92 clade bacteria are potentially important DMSP degraders and sources of climate-active gases in marine environments.

Dimethylsulfoniopropionate (DMSP) is one of Earth's most abundant organosulfur molecules, which can be catabolized by marine bacteria to release climate-active gases through the cleavage and/or demethylation pathways. The marine SAR92 clade is an abundant oligotrophic group of Gammaproteobacteria in coastal seawater, but their ability to catabolize DMSP is untested. Three SAR92 clade strains isolated from coastal seawater in this study and the SAR92 representative strain HTCC2207 were all shown to catabolize DMSP as a carbon source. All the SAR92 clade strains exhibited DMSP lyase activity producing dimethylsulfide (DMS) and their genomes encoded a ratified DddD DMSP lyase. In contrast, only HTCC2207 and two isolated strains contained the DMSP demethylase dmdA gene and potentially simultaneously demethylated and cleaved DMSP to produce methanethiol (MeSH) and DMS. In SAR92 clade strains with dddD and dmdA, transcription of these genes was inducible by DMSP substrate. Bioinformatic analysis indicated that SAR92 clade bacteria containing and transcribing DddD and DmdA were widely distributed in global oceans, especially in polar regions. This study highlights the SAR92 clade of oligotrophic bacteria as potentially important catabolizers of DMSP and sources of the climate-active gases MeSH and DMS in marine environments, particularly in polar regions.IMPORTANCECatabolism of dimethylsulfoniopropionate (DMSP) by marine bacteria has important impacts on the global sulfur cycle and climate. However, whether and how members of most oligotrophic bacterial groups participate in DMSP metabolism in marine environments remains largely unknown. In this study, by characterizing culturable strains, we have revealed that bacteria of the SAR92 clade, an abundant oligotrophic group of Gammaproteobacteria in coastal seawater, can catabolize DMSP through the DMSP lyase DddD-mediated cleavage pathway and/or the DMSP demethylase DmdA-mediated demethylation pathway to produce climate-active gases dimethylsulfide and methanethiol. Additionally, we found that SAR92 clade bacteria capable of catabolizing DMSP are widely distributed in global oceans. These results indicate that SAR92 clade bacteria are potentially important DMSP degraders and sources of climate-active gases in marine environments that have been overlooked, contributing to a better understanding of the roles and mechanisms of the oligotrophic bacteria in oceanic DMSP degradation.

DMSOP-cleaving enzymes are diverse and widely distributed in marine microorganisms.

Dimethylsulfoxonium propionate (DMSOP) is a recently identified and abundant marine organosulfur compound with roles in oxidative stress protection, global carbon and sulfur cycling and, as shown here, potentially in osmotolerance. Microbial DMSOP cleavage yields dimethyl sulfoxide, a ubiquitous marine metabolite, and acrylate, but the enzymes responsible, and their environmental importance, were unknown. Here we report DMSOP cleavage mechanisms in diverse heterotrophic bacteria, fungi and phototrophic algae not previously known to have this activity, and highlight the unappreciated importance of this process in marine sediment environments. These diverse organisms, including Roseobacter, SAR11 bacteria and Emiliania huxleyi, utilized their dimethylsulfoniopropionate lyase 'Ddd' or 'Alma' enzymes to cleave DMSOP via similar catalytic mechanisms to those for dimethylsulfoniopropionate. Given the annual teragram predictions for DMSOP production and its prevalence in marine sediments, our results highlight that DMSOP cleavage is likely a globally significant process influencing carbon and sulfur fluxes and ecological interactions.

Stabilisation of the RirA [4Fe-4S] cluster results in loss of iron-sensing function.

RirA is a global iron regulator in diverse Alphaproteobacteria that belongs to the Rrf2 superfamily of transcriptional regulators, which can contain an iron-sulfur (Fe-S) cluster. Under iron-replete conditions, RirA contains a [4Fe-4S] cluster, enabling high-affinity binding to RirA-regulated operator sequences, thereby causing the repression of cellular iron uptake. Under iron deficiency, one of the cluster irons dissociates, generating an unstable [3Fe-4S] form that subsequently degrades to a [2Fe-2S] form and then to apo RirA, resulting in loss of high-affinity DNA-binding. The cluster is coordinated by three conserved cysteine residues and an unknown fourth ligand. Considering the lability of one of the irons and the resulting cluster fragility, we hypothesized that the fourth ligand may not be an amino acid residue. To investigate this, we considered that the introduction of an amino acid residue that could coordinate the cluster might stabilize it. A structural model of RirA, based on the Rrf2 family nitrosative stress response regulator NsrR, highlighted residue 8, an Asn in the RirA sequence, as being appropriately positioned to coordinate the cluster. Substitution of Asn8 with Asp, the equivalent, cluster-coordinating residue of NsrR, or with Cys, resulted in proteins that contained a [4Fe-4S] cluster, with N8D RirA exhibiting spectroscopic properties very similar to NsrR. The variant proteins retained the ability to bind RirA-regulated DNA, and could still act as repressors of RirA-regulated genes in vivo. However, they were significantly more stable than wild-type RirA when exposed to O2 and/or low iron. Importantly, they exhibited reduced capacity to respond to cellular iron levels, even abolished in the case of the N8D version, and thus were no longer iron sensing. This work demonstrates the importance of cluster fragility for the iron-sensing function of RirA, and more broadly, how a single residue substitution can alter cluster coordination and functional properties in the Rrf2 superfamily of regulators.

Deep-sea Bacteroidetes from the Mariana Trench specialize in hemicellulose and pectin degradation typically associated with terrestrial systems.

BACKGROUND: Hadal trenches (>6000 m) are the deepest oceanic regions on Earth and depocenters for organic materials. However, how these enigmatic microbial ecosystems are fueled is largely unknown, particularly the proportional importance of complex polysaccharides introduced through deposition from the photic surface waters above. In surface waters, Bacteroidetes are keystone taxa for the cycling of various algal-derived polysaccharides and the flux of carbon through the photic zone. However, their role in the hadal microbial loop is almost unknown. RESULTS: Here, culture-dependent and culture-independent methods were used to study the potential of Bacteroidetes to catabolize diverse polysaccharides in Mariana Trench waters. Compared to surface waters, the bathypelagic (1000-4000 m) and hadal (6000-10,500 m) waters harbored distinct Bacteroidetes communities, with Mesoflavibacter being enriched at ≥ 4000 m and Bacteroides and Provotella being enriched at 10,400-10,500 m. Moreover, these deep-sea communities possessed distinct gene pools encoding for carbohydrate active enzymes (CAZymes), suggesting different polysaccharide sources are utilised in these two zones. Compared to surface counterparts, deep-sea Bacteroidetes showed significant enrichment of CAZyme genes frequently organized into polysaccharide utilization loci (PULs) targeting algal/plant cell wall polysaccharides (i.e., hemicellulose and pectin), that were previously considered an ecological trait associated with terrestrial Bacteroidetes only. Using a hadal Mesoflavibacter isolate (MTRN7), functional validation of this unique genetic potential was demonstrated. MTRN7 could utilize pectic arabinans, typically associated with land plants and phototrophic algae, as the carbon source under simulated deep-sea conditions. Interestingly, a PUL we demonstrate is likely horizontally acquired from coastal/land Bacteroidetes was activated during growth on arabinan and experimentally shown to encode enzymes that hydrolyze arabinan at depth. CONCLUSIONS: Our study implies that hadal Bacteroidetes exploit polysaccharides poorly utilized by surface populations via an expanded CAZyme gene pool. We propose that sinking cell wall debris produced in the photic zone can serve as an important carbon source for hadal heterotrophs and play a role in shaping their communities and metabolism. Video Abstract.

Cystic fibrosis survival outcomes following second lung transplant: The north American experience.

INTRODUCTION: Re-transplant is an option for those who develop end-stage lung disease due to rejection; however, little data exist following re-transplantation in cystic fibrosis (CF). METHODS: Data from the Canadian CF Registry and US CF Foundation Patient Registry supplemented with data from United Network for Organ Sharing were used. Individuals who underwent a 2nd lung transplant between 2005 and 2019 were included. The Kaplan-Meier method was used to estimate the probability of survival post-second transplant at 1, 3, and 5-years. RESULTS: Of those people who were waitlisted for a second transplant (N = 818), a total of 254 (31%) died waiting, 395 (48%) were transplanted and 169 (21%) people were alive on the waitlist. Median survival time after 2nd lung transplant was 3.3 years (95% CI: 2.8-4.1). The 1-, 3- and 5-year survival rates were 77.4% (95% CI: 73.1-82%), 52% (95% CI: 46.7-58%) and 39.4% (95% CI: 34.1-45.6%). CONCLUSIONS: Survival following second lung transplant in CF patients is lower than estimates following the first transplant. Over half of subjects who are potentially eligible for a second transplant die without receiving a second organ. This warrants further investigation.

Impact of loss to follow-up on survival estimation for cystic fibrosis.

PURPOSE: Deaths among those lost to follow-up (LTFU) in the Cystic Fibrosis Foundation Patient Registry (CFFPR) are critically important to the epidemiology of cystic fibrosis (CF). Unreported deaths could impact estimates of survival if LTFU is associated with disease trajectory. METHODS: We characterized the LTFU population (1986-2017) from the CFFPR and identified deaths via linkage with the National Death Index (NDI). Median predicted survival age and conditional survival were estimated with and without additional deaths and person-time from the NDI. RESULTS: Of the 10,582 individuals LTFU in the CFFPR, 2,460 (23.2%) matched to an NDI death record. Individuals who died after LTFU with a CF diagnosis were 43% female, 91% White/non-Hispanic, 59% had advanced CF lung disease based on last CFFPR recorded forced expiratory volume in one second (FEV1) %predicted <40 and 18% were post-lung transplant. Median predicted survival age during the most recent period available, 2013-2017, increased from 44.3 years (95% CI: 43.2, 45.7) to 45.8 years (95% CI 44.5, 47.1) with the inclusion of NDI data. CONCLUSIONS: Inclusion of deaths and additional person-time among those LTFU changed the point estimate of median predicted survival for most time periods and increased the point estimate from 2009 onwards.

Dimethylsulfoniopropionate and its catabolites are important chemical signals mediating marine microbial interactions.

Dimethylsulfoniopropionate (DMSP) is a ubiquitous organosulfur compound with key ecological roles in marine environments. This paper offers a brief insight into the mechanisms, environmental diversity, and importance of DMSP-mediated marine microbial interactions, including algae-microzooplankton interactions, bacteria-microzooplankton interactions, and algae-bacteria interactions. We also highlight current challenges that warrant further investigation.

Molecular discoveries in microbial DMSP synthesis.

Dimethylsulfoniopropionate (DMSP) is one of the Earth's most abundant organosulfur compounds because many marine algae, bacteria, corals and some plants produce it to high mM intracellular concentrations. In these organisms, DMSP acts an anti-stress molecule with purported roles to protect against salinity, temperature, oxidative stress and hydrostatic pressure, amongst many other reported functions. However, DMSP is best known for being a major precursor of the climate-active gases and signalling molecules dimethylsulfide (DMS), methanethiol (MeSH) and, potentially, methane, through microbial DMSP catabolism. DMSP catabolism has been extensively studied and the microbes, pathways and enzymes involved have largely been elucidated through the application of molecular research over the last 17 years. In contrast, the molecular biology of DMSP synthesis is a much newer field, with the first DMSP synthesis enzymes only being identified in the last 5 years. In this review, we discuss how the elucidation of key DMSP synthesis enzymes has greatly expanded our knowledge of the diversity of DMSP-producing organisms, the pathways used, and what environmental factors regulate production, as well as to inform on the physiological roles of DMSP. Importantly, the identification of key DMSP synthesis enzymes in the major groups of DMSP producers has allowed scientists to study the distribution and predict the importance of different DMSP-producing organisms to global DMSP production in diverse marine and sediment environments. Finally, we highlight key challenges for future molecular research into DMSP synthesis that need addressing to better understand the cycling of this important marine organosulfur compound, and its magnitude in the environment.

Aerobic methylation of hydrogen sulfide to dimethylsulfide in diverse microorganisms and environments.

Dimethylsulfide (DMS) is the major biosulfur source emitted to the atmosphere with key roles in global sulfur cycling and potentially climate regulation. The main precursor of DMS is thought to be dimethylsulfoniopropionate. However, hydrogen sulfide (H2S), a widely distributed and abundant volatile in natural environments, can be methylated to DMS. The microorganisms and the enzymes that convert H2S to DMS, and their importance in global sulfur cycling were unknown. Here we demonstrate that the bacterial MddA enzyme, previously known as a methanethiol S-methyltransferase, could methylate inorganic H2S to DMS. We determine key residues involved in MddA catalysis and propose the mechanism for H2S S-methylation. These results enabled subsequent identification of functional MddA enzymes in abundant haloarchaea and a diverse range of algae, thus expanding the significance of MddA mediated H2S methylation to other domains of life. Furthermore, we provide evidence for H2S S-methylation being a detoxification strategy in microorganisms. The mddA gene was abundant in diverse environments including marine sediments, lake sediments, hydrothermal vents and soils. Thus, the significance of MddA-driven methylation of inorganic H2S to global DMS production and sulfur cycling has likely been considerably underestimated.

Disruption in Blood Pressure Control With the COVID-19 Pandemic: The PCORnet Blood Pressure Control Laboratory.

OBJECTIVE: To explore trends in blood pressure (BP) control before and during the COVID-19 pandemic. PATIENTS AND METHODS: Health systems participating in the National Patient-Centered Clinical Research Network (PCORnet) Blood Pressure Control Laboratory Surveillance System responded to data queries, producing 9 BP control metrics. Averages of the BP control metrics (weighted by numbers of observations in each health system) were calculated and compared between two 1-year measurement periods (January 1, 2019, through December 31, 2019, and January 1, 2020, through December 31, 2020). RESULTS: Among 1,770,547 hypertensive persons in 2019, BP control to <140/<90 mm Hg varied across 24 health systems (range, 46%-74%). Reduced BP control occurred in most health systems with onset of the COVID-19 pandemic; the weighted average BP control was 60.5% in 2019 and 53.3% in 2020. Reductions were also evident for BP control to <130/<80 mm Hg (29.9% in 2019 and 25.4% in 2020) and improvement in BP (reduction of 10 mm Hg in systolic BP or achievement of systolic BP <140 mm Hg; 29.7% in 2019 and 23.8% in 2020). Two BP control process metrics exhibited pandemic-associated disruption: repeat visit in 4 weeks after a visit with uncontrolled hypertension (36.7% in 2019 and 31.7% in 2020) and prescription of fixed-dose combination medications among those with 2 or more drug classes (24.6% in 2019 and 21.5% in 2020). CONCLUSION: BP control decreased substantially during the COVID-19 pandemic, with a corresponding reduction in follow-up health care visits among persons with uncontrolled hypertension. It is unclear whether the observed decline in BP control during the pandemic will contribute to future cardiovascular events.

Cystic fibrosis prevalence in the United States and participation in the Cystic Fibrosis Foundation Patient Registry in 2020.

BACKGROUND: The Cystic Fibrosis Foundation Patient Registry (CFFPR) collects data on individuals with cystic fibrosis (CF) in the United States (US). In 2012, the US CF population was estimated at 33,292 to 34,327 individuals, with 81-84% CFFPR participation. METHODS: In this study, we update these estimates via simulation to account for uncertainty in CF incidence by race or Hispanic ethnicity, initiation of CF newborn screening (NBS) programs by state, and updated cumulative survival for CF births 1968-2020. We defined registry participation as the proportion of individuals alive as of 2020 with any prior CFFPR participation as well as the proportion with contributing data in 2019 or 2020; we summarize CFFPR participation for those born prior to 1968. RESULTS: We estimated the 2020 prevalent CF population between 1968-2020 to be 38,804 (95% Uncertainty Interval (UI): 38,532 to 39,065) individuals, with 77% of the prevalent CF population contributing recent data. CFFPR participation differs by age (54% of those born in 1968) and exceeds >90% of the population born in 2009 or later. CONCLUSIONS: We demonstrate that the CFFPR remains a valid data source generalizable to the CF population. High participation among younger individuals may reflect the success of newborn screening programs and early referral to CF care. If engagement can be sustained, the percentage of individuals participating in the CFFPR will grow over time and there is an opportunity to identify factors associated with loss to follow up among older individuals to optimize the quality of the CFFPR data.

A new dimethylsulfoniopropionate lyase of the cupin superfamily in marine bacteria.

Dimethylsulfoniopropionate (DMSP) is a marine organosulfur compound with important roles in stress protection, marine biogeochemical cycling, chemical signalling and atmospheric chemistry. Diverse marine microorganisms catabolize DMSP via DMSP lyases to generate the climate-cooling gas and info-chemical dimethyl sulphide. Abundant marine heterotrophs of the Roseobacter group (MRG) are well known for their ability to catabolize DMSP via diverse DMSP lyases. Here, a new DMSP lyase DddU within the MRG strain Amylibacter cionae H-12 and other related bacteria was identified. DddU is a cupin superfamily DMSP lyase like DddL, DddQ, DddW, DddK and DddY, but shares <15% amino acid sequence identity with these enzymes. Moreover, DddU proteins forms a distinct clade from these other cupin-containing DMSP lyases. Structural prediction and mutational analyses suggested that a conserved tyrosine residue is the key catalytic amino acid residue in DddU. Bioinformatic analysis indicated that the dddU gene, mainly from Alphaproteobacteria, is widely distributed in the Atlantic, Pacific, Indian and polar oceans. For reference, dddU is less abundant than dddP, dddQ and dddK, but much more frequent than dddW, dddY and dddL in marine environments. This study broadens our knowledge on the diversity of DMSP lyases, and enhances our understanding of marine DMSP biotransformation.

Ubiquitous occurrence of a dimethylsulfoniopropionate ABC transporter in abundant marine bacteria.

Dimethylsulfoniopropionate (DMSP) is a ubiquitous organosulfur compound in marine environments with important functions in both microorganisms and global biogeochemical carbon and sulfur cycling. The SAR11 clade and marine Roseobacter group (MRG) represent two major groups of heterotrophic bacteria in Earth's surface oceans, which can accumulate DMSP to high millimolar intracellular concentrations. However, few studies have investigated how SAR11 and MRG bacteria import DMSP. Here, through comparative genomics analyses, genetic manipulations, and biochemical analyses, we identified an ABC (ATP-binding cassette)-type DMSP-specific transporter, DmpXWV, in Ruegeria pomeroyi DSS-3, a model strain of the MRG. Mutagenesis suggested that DmpXWV is a key transporter responsible for DMSP uptake in strain DSS-3. DmpX, the substrate binding protein of DmpXWV, had high specificity and binding affinity towards DMSP. Furthermore, the DmpX DMSP-binding mechanism was elucidated from structural analysis. DmpX proteins are prevalent in the numerous cosmopolitan marine bacteria outside the SAR11 clade and the MRG, and dmpX transcription was consistently high across Earth's entire global ocean. Therefore, DmpXWV likely enables pelagic marine bacteria to efficiently import DMSP from seawater. This study offers a new understanding of DMSP transport into marine bacteria and provides novel insights into the environmental adaption of marine bacteria.

Improvement in Blood Pressure Control in Safety Net Clinics Receiving 2 Versions of a Scalable Quality Improvement Intervention: BP MAP A Pragmatic Cluster Randomized Trial.

Background Uncontrolled blood pressure (BP) remains a leading cause of death in the United States. The American Medical Association developed a quality improvement program to improve BP control, but it is unclear how to efficiently implement this program at scale across multiple health systems. Methods and Results We conducted BP MAP (Blood Pressure Measure Accurately, Act Rapidly, and Partner With Patients), a comparative effectiveness trial with clinic-level randomization to compare 2 scalable versions of the quality improvement program: Full Support (with support from quality improvement expert) and Self-Guided (using only online materials). Outcomes were clinic-level BP control (<140/90 mm Hg) and other BP-related process metrics calculated using electronic health record data. Difference-in-differences were used to compare changes in outcomes from baseline to 6 months, between intervention arms, and to a nonrandomized Usual Care arm composed of 18 health systems. A total of 24 safety-net clinics in 9 different health systems underwent randomization and then simultaneous implementation. BP control increased from 56.7% to 59.1% in the Full Support arm, and 62.0% to 63.1% in the Self-Guided arm, whereas BP control dropped slightly from 61.3% to 60.9% in the Usual Care arm. The between-group differences-in-differences were not statistically significant (Full Support versus Self-Guided=+1.2% [95% CI, -3.2% to 5.6%], P=0.59; Full Support versus Usual Care=+3.2% [-0.5% to 6.9%], P=0.09; Self-Guided versus Usual Care=+2.0% [-0.4% to 4.5%], P=0.10). Conclusions In this randomized trial, 2 methods of implementing a quality improvement intervention in 24 safety net clinics led to modest improvements in BP control that were not statistically significant. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03818659.

Aminolipids elicit functional trade-offs between competitiveness and bacteriophage attachment in Ruegeria pomeroyi.

Lipids play a crucial role in maintaining cell integrity and homeostasis with the surrounding environment. Cosmopolitan marine roseobacter clade (MRC) and SAR11 clade bacteria are unique in that, in addition to glycerophospholipids, they also produce an array of amino acid-containing lipids that are conjugated with beta-hydroxy fatty acids through an amide bond. Two of these aminolipids, the ornithine aminolipid (OL) and the glutamine aminolipid (QL), are synthesized using the O-acetyltransferase OlsA. Here, we demonstrate that OL and QL are present in both the inner and outer membranes of the Gram-negative MRC bacterium Ruegeria pomeroyi DSS-3. In an olsA mutant, loss of these aminolipids is compensated by a concurrent increase in glycerophospholipids. The inability to produce aminolipids caused significant changes in the membrane proteome, with the membrane being less permeable and key nutrient transporters being downregulated while proteins involved in the membrane stress response were upregulated. Indeed, the import of 14C-labelled choline and dimethylsulfoniopropionate, as a proxy for the transport of key marine nutrients across membranes, was significantly impaired in the olsA mutant. Moreover, the olsA mutant was significantly less competitive than the wild type (WT) being unable to compete with the WT strain in co-culture. However, the olsA mutant unable to synthesize these aminolipids is less susceptible to phage attachment. Together, these data reveal a critical role for aminolipids in the ecophysiology of this important clade of marine bacteria and a trade-off between growth and avoidance of bacteriophage attachment.

Quorum Sensing Regulates the Production of Methanethiol in Vibrio harveyi.

Methanethiol (MeSH) and dimethyl sulfide (DMS) are important volatile organic sulfur compounds involved in atmospheric chemistry and climate regulation. However, little is known about the metabolism of these compounds in the ubiquitous marine vibrios. Here, we investigated MeSH/DMS production and whether these processes were regulated by quorum-sensing (QS) systems in Vibrio harveyi BB120. V. harveyi BB120 exhibited strong MeSH production from methionine (Met) (465 nmol mg total protein-1) and weak DMS production from dimethylsulfoniopropionate (DMSP) cleavage. The homologs of MegL responsible for MeSH production from L-Met widely existed in vibrio genomes. Using BB120 and its nine QS mutants, we found that the MeSH production was regulated by HAI-1, AI-2 and CAI-1 QS pathways, as well as the luxO gene located in the center of this QS cascade. The regulation role of HAI-1 and AI-2 QS systems in MeSH production was further confirmed by applying quorum-quenching enzyme MomL and exogenous autoinducer AI-2. By contrast, the DMS production from DMSP cleavage showed no significant difference between BB120 and its QS mutants. Such QS-regulated MeSH production may help to remove excess Met that can be harmful for vibrio growth. These results emphasize the importance of QS systems and the MeSH production process in vibrios.