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1.
Bioresour Technol ; 319: 124036, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33032187

RESUMO

Due to their broad-spectrum antibacterial activity and low cost, tetracyclines (TCs) are a class of antibiotics widely used for human and veterinary medical purposes and as a growth-promoting agent for aquaculture. Interrelationships between TCs and nitrogen cycling have attracted scientific attention due to the complicated processes mediated by microorganisms. TCs negatively impact the nitrogen cycling; however, simultaneous degradation of TCs during nitrogen cycling mediated by microorganisms can be achieved. This review encapsulates the background and distribution of TCs in the environment. Additionally, the main nitrogen cycling process mediated by microorganisms were retrospectively examined. Furthermore, effects of TCs on the nitrogen cycling processes, namely nitrification, denitrification, and anammox, have been summarized. Finally, the pathway and microbial mechanism of degradation of TCs accompanied by nitrogen cycling processes were reviewed, along with the scope for prospective studies.

2.
Clin Transl Sci ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33202102

RESUMO

Voriconazole is the mainstay for the treatment of invasive fungal infections in patients with kidney transplant. Variant CYP2C19 alleles, hepatic function, and concomitant medications are directly involved in the metabolism of voriconazole. However, the drug is also associated with numerous adverse events. The purpose of this study was to identify predictors of adverse events using binary logistic regression and to measure its trough concentration using multiple linear modeling. We conducted a prospective analysis of 93 kidney recipients co-treated with voriconazole and recorded 213 trough concentrations of it. Predictors of the adverse events were voriconazole trough concentration with the odds ratios (OR) of 2.614(P=0.016), cytochrome P450 2C19(CYP2C19), and hemoglobin (OR:0.181; P=0.005). The predictive power of these three factors was 91.30%. We also found that CYP2C19 phenotypes, hemoglobin, platelet count, and concomitant use of ilaprazole had quantitative relationships with voriconazole trough concentration. The fit coefficient of this regression equation was R2 =0.336, demonstrating that the model explained 33.60% of interindividual variability in the disposition of voriconazole. In conclusion, predictors of adverse events are CYP2C19 phenotypes, hemoglobin and voriconazole trough concentration. Determinants of the voriconazole trough concentration were CYP2C19 phenotypes, platelet count, hemoglobin, concomitant use of ilaprozole. If we consider these factors during voriconazole use, we are likely to maximize the treatment effect and minimize adverse events.

3.
Sheng Wu Gong Cheng Xue Bao ; 36(10): 1992-2000, 2020 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-33169565

RESUMO

Hepatocellular carcinoma (HCC) is one of the five most common malignant tumors. According to the latest statistics of the World Health Organization (WHO), the incident and mortality rates of HCC ranks the eighth and third in the world, respectively, which severely affect people's health. Exosomes are extracellular vesicles with a bilayer of phospholipids, which carry active substances such as proteins and nucleic acids derived from their mother cells. These exosomes greatly facilitate the exchange of substances and information between cells, and coordinate physiological and pathological processes in the body. In recent years, a large number of studies have shown that exosomal proteins play important roles in the tumorigenesis, development, diagnosis and treatment of HCC. Here we review the composition and functions of exosomes and the role of exosomal proteins in HCC.


Assuntos
Carcinoma Hepatocelular , Exossomos , Neoplasias Hepáticas , Proteômica , Carcinogênese/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/fisiopatologia , Carcinoma Hepatocelular/terapia , Exossomos/genética , Exossomos/metabolismo , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/fisiopatologia , Neoplasias Hepáticas/terapia , MicroRNAs/genética
4.
Artigo em Inglês | MEDLINE | ID: mdl-33226767

RESUMO

Plasmonics has emerged as a promising methodology to promote chemical reactions and has become a field of intense research effort. Ag nanoparticles (NPs) as plasmonic catalysts have been extensively studied because of their remarkable optical properties. This review analyzes the emergence and development of localized surface plasmon resonance (LSPR) in organic chemistry, mainly focusing on the discovery of novel reactions with new mechanisms on Ag NPs. Initially, the basics of LSPR and LSPR-promoted photocatalytic mechanisms are illustrated. Then, the recent advances in plasmonic nanosilver-mediated photocatalysis in organic transformations are highlighted with an emphasis on the related reaction mechanisms. Finally, a proper perspective on the remaining challenges and future directions in the field of LSPR-promoted organic transformations is proposed.

5.
J Healthc Eng ; 2020: 8840910, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33178407

RESUMO

With the increasing emphasis on remote electrocardiogram (ECG) monitoring, a variety of wearable remote ECG monitoring systems have been developed. However, most of these systems need improvement in terms of efficiency, stability, and accuracy. In this study, the performance of an ECG monitoring system is optimized by improving various aspects of the system. These aspects include the following: the judgment, marking, and annotation of ECG reports using artificial intelligence (AI) technology; the use of Internet of Things (IoT) to connect all the devices of the system and transmit data and information; and the use of a cloud platform for the uploading, storage, calculation, and analysis of patient data. The use of AI improves the accuracy and efficiency of ECG reports and solves the problem of the shortage and uneven distribution of high-quality medical resources. IoT technology ensures the good performance of remote ECG monitoring systems in terms of instantaneity and rapidity and, thus, guarantees the maximum utilization efficiency of high-quality medical resources. Through the optimization of remote ECG monitoring systems with AI and IoT technology, the operating efficiency, accuracy of signal detection, and system stability have been greatly improved, thereby establishing an excellent health monitoring and auxiliary diagnostic platform for medical workers and patients.

6.
Opt Lett ; 45(22): 6298-6301, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-33186974

RESUMO

Quantum entanglement enables measurement on one party to affect the other's state. Based on this peculiar feature, we propose a model of remote-controlled quantum computing and design an optical scheme to realize this model for a single qubit. As an experimental demonstration of this scheme, we further implement three Pauli operators, Hardmard gate, phase gate, and π/8 gate. The minimal fidelity obtained by quantum process tomography reaches 82%. Besides, as a potential application, our model contributes to secure remote quantum information processing.

7.
Nanotechnology ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176292

RESUMO

The mechanism of nanofiltration (NF) membrane separation of Mg2+ and Li+ needs to be further investigated, but some commonly used model theories are abstract, which makes them difficult to understand. More importantly, the relationship between membrane charge and separation performance of Mg2+ and Li+ cannot be quantitatively analyzed. It is worth to study those challenges and provide a performance boost for Mg2+/Li+ filtration applications of NF membranes. Here, various NF membranes with the membrane volumetric charge density increasing from -4.69 to 7.02 mol•m-3 were fabricated via interfacial polymerization. For these membranes, the separation factor SMg,Li were decreased from 0.41 to 0.20. Importantly, the visual simulation results were consistent with the experimental results as a whole. The separation factor SMg,Li decreased with the increase of volumetric charge density, and the minimum separation factor SMg,Li of NF membranes was 0.20 (experiment) and 0.17 (simulation), respectively. This manifested that the performance of positive charged NF membrane had not fully been developed. Furthermore, we analyzed further the relationship between membrane charge and separation performance, and visualized the simulation of NF membrane filtration and separation.

8.
J Proteome Res ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33172275

RESUMO

The Chromosome-Centric Human Proteome Project (C-HPP) was launched in 2012 to perfect the annotation of human protein existence by identifying stronger evidence of the expression of missing proteins (MPs) at the protein level. After an 8 year effort all over the world, the number of MPs in the neXtProt database significantly decreased from 5511 (2012-02-24) to 1899 (2020-01-17). It is now more difficult to provide confident evidence of the remaining MPs because of their specific characteristics, including low abundance, low molecular weight, unexpected modifications, transmembrane structure, tissue-expression specificity, and so on. A higher resolution mass spectrometry (MS) interpretation engine might provide an opportunity to identify these buried MPs in complex samples by the combination with multi-tissue large-scale proteomics. In this study, open-pFind was used to dig MPs from 20 pairs of healthy human tissues by Wang et al. ( Mol. Syst. Biol. 2019, 15 (2), e8503) combined with our large-scale testis data set digested by three enzymes (Glu-C, Lys-C, and trypsin) with specificity for different amino acid residues ( J. Proteme Res. 2019, 18 (12), 4189-4196). A total of 1 535 536 peptides with 17 283 477 peptide-spectrum matches (PSMs) were mapped to 14 279 protein entries at a false discovery rate of <1% at the PSM, peptide, and protein levels. A total of 103 MP candidates were identified, among which 86 candidates had more unique peptide numbers compared with our single testis tissue. After rigorous screening, manual checks, peptide synthesis, and matching with documented peptides from PeptideAtlas, we validated four MPs, P0C7T8 (duodenum and small intestine), Q8WWZ4 (stomach and rectum), Q8IV35 (fallopian tube), and O14921 (tonsil), at the protein level. All MS raw files have been deposited to the ProteomeXchange with identifier PXD021391.

9.
BMC Med Genet ; 21(1): 213, 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33129279

RESUMO

BACKGROUND: Stargardt disease (STGD1) is a common recessive hereditary macular dystrophy in early adulthood or childhood, with an estimated prevalence of 1:8000 to 1:10,000. ABCA4 is the causative gene for STGD1. The current study aims at identifying the novel disease-related ABCA4 variants in Han Chinese families with STGD1 using next-generation sequencing (NGS). METHODS: In the present study, 12 unrelated Han Chinese families (19 males and 17 females) with STGD1 were tested by panel-based NGS. In order to capture the coding exons and the untranslated regions (UTRs) plus 30 bp of intronic flanking sequences of 792 genes, which were closely associated with usual ophthalmic genetic disease, we designed a customized panel, namely, Target_Eye_792_V2 chip. STGD1 patients were clinically diagnosed by experienced ophthalmologists. All the detected variants were filtered and analyzed through the public databases and in silico programs to assess potential pathogenicity. RESULTS: Twenty-one ABCA4 mutant variants were detected in 12 unrelated Han Chinese families with STGD1, containing 14 missense, three splicing, two frameshift, one small deletion, and one nonsense variants. Base on the American College of Medical Genetics (ACMG) guidelines, 8 likely pathogenic and 13 pathogenic variants were determined. The functional consequences of these mutant variants were predicted through in silico programs. Of the 21 mutant variants in ABCA4, two novel coding variants c.3017G > A and c.5167 T > C and one novel null variant c.3051-1G > A were detected in three unrelated probands. CONCLUSIONS: By panel-based NGS, 21 ABCA4 variants were confirmed in 12 unrelated Han Chinese families. Among them, 3 novel mutant variants were found, which further expanded the ABCA4 mutation spectrum in STGD1 patients.

10.
Front Immunol ; 11: 562138, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33133072

RESUMO

Objective: Anti-DFS70 antibodies correlating with the nuclear dense fine speckled (DFS) pattern in the HEp-2 indirect immunofluorescence assay (IFA) are less common in patients with systemic autoimmune rheumatic disease (SARD) than in healthy subjects and their clinical associations remain elusive. We hosted a multi-center HEp-2 IFA training program to improve the ability of clinical laboratories to recognize the DFS pattern and to investigate the prevalence and relevance of anti-DFS70 antibodies. Methods: DFS pattern sera identified by HEp-2 IFA in 29 centers in China were redirected to a central laboratory for anti-DFS70 testing by line immunoblot assay (LIA), enzyme-linked immunosorbent assay (ELISA), and IFA with HEp-2 ELITE/DFS70-KO substrate. Anti-extractable nuclear antigen antibodies were measured by LIA and the clinical relevance was examined in adult and pediatric patients. Results: HEp-2 IFA positive rate and DFS pattern in positive sera were 36.2% (34,417/95,131) and 1.7% (582/34,417) in the patient cohort, and 10.0% (423/4,234) and 7.8% (33/423) in a healthy population, respectively. Anti-DFS70 prevalence among sera presenting the DFS pattern was 96.0, 93.7, and 49.6% by ELISA, LIA, and HEp-2 ELITE, respectively. 15.5% (52/336) of adult and 50.0% (20/40) of pediatric anti-DFS70 positive patients were diagnosed with SARD. Diseases most common in anti-DFS70 positive patients were spontaneous abortion (28.0%) in adults and juvenile idiopathic arthritis (22.5%) in pediatric patients. Conclusion: Accurate DFS pattern identification increased the detection rate of anti-DFS70 antibodies by ELISA and LIA. Anti-DFS70 antibodies are remarkably high in cases of spontaneous abortion and in pediatric SARD patients, but not prevalent in adult SARD patients.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33140637

RESUMO

The development of photovoltaic devices with a high output voltage offers great opportunities for emerging internet of things (IoT) sensors and low-power-consumption electronics. However, the photovoltage of solar cells is yet to satisfy the requirement of driving voltage for most applications. Here, we demonstrate a wide-band gap CsPbBr3-based solar cell with a heterostructured light absorber based on amino acid-modulated CsPbBr3 and CdSe quantum dots (QDs). Compared with the single absorbing layer device, the heterostructured device exhibits a low nonradiative recombination loss, which is strongly correlated to the high external electroluminescence of the device. In addition, in the heterostructured solar cells, carrier transfer from the perovskite to CdSe QDs induces the conduction band bending of CdSe QDs, leading to a large splitting of the quasi-Fermi levels. As a result, a remarkable photovoltage up to 1.75 V is achieved for the wide-band gap solar cells, representing an extremely low voltage deficit of 250 mV. Furthermore, the CsPbBr3-based solar cells exhibit a weak light intensity dependence, showing a photovoltage of 1.59 V under room light conditions. Our work not only provides an effective approach for the design of high-photovoltage solar cells but also paves the ways of using photovoltaic devices for various applications with low driving voltage schemes.

12.
J Transl Med ; 18(1): 381, 2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-33032623

RESUMO

BACKGROUND AND OBJECTIVES: Sepsis is a leading cause of mortality and morbidity in the intensive care unit. Regulatory mechanisms underlying the disease progression and prognosis are largely unknown. The study aimed to identify master regulators of mortality-related modules, providing potential therapeutic target for further translational experiments. METHODS: The dataset GSE65682 from the Gene Expression Omnibus (GEO) database was utilized for bioinformatic analysis. Consensus weighted gene co-expression netwoek analysis (WGCNA) was performed to identify modules of sepsis. The module most significantly associated with mortality were further analyzed for the identification of master regulators of transcription factors and miRNA. RESULTS: A total number of 682 subjects with various causes of sepsis were included for consensus WGCNA analysis, which identified 27 modules. The network was well preserved among different causes of sepsis. Two modules designated as black and light yellow module were found to be associated with mortality outcome. Key regulators of the black and light yellow modules were the transcription factor CEBPB (normalized enrichment score = 5.53) and ETV6 (NES = 6), respectively. The top 5 miRNA regulated the most number of genes were hsa-miR-335-5p (n = 59), hsa-miR-26b-5p (n = 57), hsa-miR-16-5p (n = 44), hsa-miR-17-5p (n = 42), and hsa-miR-124-3p (n = 38). Clustering analysis in 2-dimension space derived from manifold learning identified two subclasses of sepsis, which showed significant association with survival in Cox proportional hazard model (p = 0.018). CONCLUSIONS: The present study showed that the black and light-yellow modules were significantly associated with mortality outcome. Master regulators of the module included transcription factor CEBPB and ETV6. miRNA-target interactions identified significantly enriched miRNA.

13.
Phys Rev Lett ; 125(15): 150401, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33095624

RESUMO

In quantum mechanics, geometry has been demonstrated as a useful tool for inferring nonclassical behaviors and exotic properties of quantum systems. One standard approach to illustrate the geometry of quantum systems is to project the quantum state space onto the Euclidean space via measurements of observables on the system. Despite the great success of this method in studying two-level quantum systems (qubits) with the celebrated Bloch sphere representation, it is still difficult to reveal the geometry of multidimensional quantum systems. Here we report the first experiment measuring the geometry of such projections beyond the qubit. Specifically, we observe the joint numerical ranges of a triple of observables in a three-level photonic system, providing a complete classification of these ranges. We further show that the geometry of different classes reveals ground-state degeneracies of a Hamiltonian as a linear combination of the observables, which is related to quantum phases in the thermodynamic limit. Our results offer a versatile geometric approach for exploring the properties of higher-dimensional quantum systems.

14.
Acta Ophthalmol ; 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33124204

RESUMO

PURPOSE: To provides the clinical and genetic characteristics of a series of Chinese patients with X-linked juvenile retinoschisis (XLRS) through multimodal imaging and next-generation sequencing. METHODS: Thirty patients (60 eyes) from 29 unrelated families of Chinese origin with XLRS were screened using multigene panel testing, and underwent a complete clinical evaluation. All variants identified in this study and reported in the Human Gene Mutation Database were analysed. RESULTS: Twenty-five distinct variants in the retinoschisin gene were identified, of which eight were novel, and one was de novo. Missense mutations were the most prevalent type, and mutation hot spot was localized in the discoidin domain. The mean Snellen best-corrected visual acuity was 0.28 ± 0.17. Of all eyes presenting with schisis, 92.86% had lamellar schisis and 62.5% had peripheral schisis. Schisis changes mostly involved inner and outer nuclear layers. X-linked juvenile retinoschisis (XLRS) patients had a high incidence of complications, and peripheral schisis was a risk factor for it. No obvious genotype-phenotype association was observed. CONCLUSION: This study provides comprehensive analyses of the genetic and clinical characteristics of XLRS in a cohort of Chinese patients. The fourth de novo mutation in RS1 was identified. And we show that XLRS has a wide spectrum of clinical characteristics; hence, molecular diagnosis is crucial for its diagnosis, differential diagnosis and genetic counselling. Peripheral schisis is a risk factor for the high incidence of complications, and no clear genotype-phenotype correlations were found.

15.
Mol Plant Pathol ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33029873

RESUMO

Plant pathogens deliver virulence effectors into plant cells to modulate plant immunity and facilitate infection. Although species-specific virulence effector screening approaches have been developed for several pathogens, these assays do not apply to pathogens that cannot be cultured and/or transformed outside of their hosts. Here, we established a rapid and parallel screening assay, called the virus-induced virulence effector (VIVE) assay, to identify putative effectors in various plant pathogens, including unculturable pathogens, using a virus-based expression vector. The VIVE assay uses the potato virus X (PVX) vector to transiently express candidate effector genes of various bacterial and fungal pathogens into Nicotiana benthamiana leaves. Using the VIVE assay, we successfully identified Avh148 as a potential virulence effector of Phytophthora sojae. Plants infected with PVX carrying Avh148 showed strong viral symptoms and high-level Avh148 and viral RNA accumulation. Analysis of P. sojae Avh148 deletion mutants and soybean hairy roots overexpressing Avh148 revealed that Avh148 is required for full pathogen virulence. In addition, the VIVE assay was optimized in N. benthamiana plants at different developmental stages across a range of Agrobacterium cell densities. Overall, we identified six novel virulence effectors from seven pathogens, thus demonstrating the broad effectiveness of the VIVE assay in plant pathology research.

16.
Chem Commun (Camb) ; 56(78): 11669-11672, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33000808

RESUMO

We have developed a DPPE-catalyzed three molecular two component tandem reaction of γ-substituted allenoate and CS2 to construct 2-thineyl vinyl sulfide through phosphine catalyzed [3+2] cyclization followed by Michael addition. The synthetic value of the 2-thineyl vinyl sulfide was demonstrated by a concise synthesis of an anti-glaucoma agent.

17.
Small ; : e2003407, 2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33015974

RESUMO

Carbon materials with multilevel structural features are showing great potentials in electromagnetic (EM) pollution precaution. With ZIF-67 microcubes as a self-sacrificing precursor, hierarchical carbon microcubes with micro/mesoporous shells and hollow cavities have been successfully fabricated with the assistance of rigid SiO2 coating layers. It is found that the SiO2 layer can effectively counteract the inward shrinkage of organic frameworks during high-temperature pyrolysis due to intensive interfacial interaction. The obtained hollow porous carbon microcubes (HPCMCs) exhibit larger Brunauer-Emmett-Teller surface area and pore volume than porous carbon microcubes (PCMCs) directly derived from ZIF-67 microcubes. The unique microstructure is confirmed to be favorable for conductive loss and interfacial polarization, thus boosting the overall dielectric loss capability of carbon materials. Besides, hollow cavity will also promote multiple reflection of incident EM waves and intensify the dissipation of EM energy. As expected, HPCMCs harvest better microwave absorption performance, including strong reflection loss intensity and broad response bandwidth, than many traditional microporous/mesoporous carbon materials. This study provides a new strategy for the construction of hierarchical carbon materials and may inspire the design of carbon-based composites with excellent EM functions.

18.
Food Funct ; 11(10): 8987-8995, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33001081

RESUMO

Obesity is an increasingly severe global health problem, leading to chronic inflammation and metabolic disorders in both peripheral tissues and the central nervous system. Matcha is a powdered green tea, and it is very popular in recent years as a beverage and food additive. Matcha green tea has been reported to have outstanding potential in regulating obesity-related metabolic syndrome. However, there are few studies on the regulation mechanism of matcha green tea on the central nervous system. In this study, we established a high-fat diet-induced obese mouse model. The results showed that dietary supplementation with matcha could effectively inhibit the weight gain, fat accumulation, glycemia and lipidemia increase, and excessive activation of microglia in the arcuate nucleus of the hypothalamus. Furthermore, we used different concentrations (100%, 80%, 60%, 40%, and 20%, v/v) of ethanol solution to prepare matcha ethanol extracts, and investigated their effects on palmitic acid-induced inflammation of microglial BV-2 cells. The results showed that matcha ethanol extracts could significantly reduce the release of inflammatory cytokines and the expression and phosphorylation of JAK2 and STAT3.

19.
J Int Med Res ; 48(10): 300060520960317, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33044102

RESUMO

OBJECTIVE: To explore a method for evaluating the bioequivalence of acarbose based on pharmacodynamic parameters using a single-dose, randomized-sequence, three-way crossover study of acarbose test (T) and reference (R) formulations. METHODS: Baseline-adjusted, pre-dose value deduction, and direct comparison methods were used to evaluate the geometric T/R ratios and 90% confidence intervals (CIs) of the ln-transformed pharmacodynamic parameters to identify the most suitable evaluation system. Twelve participants were randomly divided into three groups to receive treatment in the following sequences: TRR, RTR, and RRT, each including a 7-day washout period between treatment periods. The serum glucose concentration (baseline) was determined. Pharmacodynamic parameters, including the maximum reduction in serum glucose concentrations (ΔCSG,max) and difference of the AUC of glucose between before and after acarbose exposure (ΔAUEC), were tested. RESULTS: Using the direct comparison method, the geometric mean ratios of CSG,max, AUEC(0-2h), and AUEC(0-4h) were 94.13%, 97.82% and 99.76%, respectively. The 90% CIs of the geometric T/R ratios for CSG,max, AUEC(0-2h), and AUEC(0-4h) all fell between 80% and 125%. Conversely, ΔCSG,max and ΔAUEC(0-4h) were less reliable measures of acarbose bioequivalence. CONCLUSIONS: Pre-dose value deduction and direct comparison methods can be initially considered suitable for assessing acarbose bioequivalence.

20.
Mol Microbiol ; 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33084151

RESUMO

Streptococcus sanguinis is a primary colonizer of teeth and is associated with oral health. When it enters the bloodstream, however, this bacterium may cause the serious illness infective endocarditis. The genes required for survival and proliferation in blood have not been identified. The products of these genes could provide a rich source of targets for endocarditis-specific antibiotics possessing greater efficacy for endocarditis, but also little or no activity against those bacteria that remain in the mouth. We previously created a comprehensive library of S. sanguinis mutants lacking every non-essential gene. We have now screened each member of this library for growth in human serum and discovered 178 mutants with significant abundance changes. The main biological functions disrupted in these mutants, including purine metabolism, were highlighted via network analysis. The components of an ECF-family transporter were required for growth in serum and were shown for the first time in any bacterium to be essential for endocarditis virulence. We also identified two mutants whose growth was reduced in serum but not in saliva. This strategy promises to enable selective targeting of bacteria based on their location in the body, in this instance, treating or preventing endocarditis while leaving the oral microbiome intact.

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