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1.
Microbiol Spectr ; : e0037524, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39115309

RESUMEN

Klebsiella pneumoniae has emerged as a global health threat due to its role in the spread of antimicrobial resistance and because it is a frequent cause of hospital-acquired infections and neonatal sepsis. Capsular and lipopolysaccharide (LPS) O-antigen polysaccharide surface antigens are major immunogens that are useful for strain classification and are candidates for vaccine development. We have developed real-time PCR reagents for molecular serotyping, subtyping, and quantitation of the most prevalent LPS O-antigen types (i.e., O1, O2, O3, and O5) of Klebsiella pneumoniae. We describe two applications for this O-typing assay: for screening culture isolates and for direct typing of Klebsiella pneumoniae present in stool samples. We find 100% concordance between the results of the O-typing assay and whole-genome sequencing of 81 culture isolates, and >90% agreement in O-typing performed directly on specimens of human stool, with disagreement arising primarily from a lack of sensitivity of the culture-based comparator method. Additionally, we find evidence for mixed O-type populations at varying levels of abundance in direct tests of stool from a hospitalized patient population. Taken together, these results demonstrate that this novel O-typing assay can be a useful tool for K. pneumoniae epidemiologic and vaccine studies.IMPORTANCEKlebsiella pneumoniae is an important opportunistic pathogen. The gastrointestinal (GI) tract is the primary reservoir of K. pneumoniae in humans, and GI carriage is believed to be a prerequisite for invasive infection. Knowledge about the dynamics and duration of GI carriage has been hampered by the lack of tools suitable for detection and strain discrimination. Real-time PCR is particularly suited to the higher-throughput workflows used in population-based studies, which are needed to improve our understanding of carriage dynamics and the factors influencing K. pneumoniae colonization.

2.
bioRxiv ; 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38746292

RESUMEN

Background: Klebsiella pneumonia (Kpn) is the fourth leading cause of infection-related deaths globally, yet little is known about human antibody responses to invasive Kpn. In this study, we sought to determine whether the O-specific polysaccharide (OPS) antigen, a vaccine candidate, is immunogenic in humans with Kpn bloodstream infection (BSI). We also sought to define the cross-reactivity of human antibody responses among structurally related Kpn OPS subtypes and to assess the impact of capsule production on OPS-targeted antibody binding and function. Methods: We measured plasma antibody responses to OPS (and MrkA, a fimbrial protein) in a cohort of patients with Kpn BSI and compared these with controls, including a cohort of healthy individuals and a cohort of individuals with Enterococcus BSI. We performed flow cytometry to measure the impact of Kpn capsule production on whole cell antibody binding and complement deposition, utilizing patient isolates with variable levels of capsule production and isogenic capsule-deficient strains derived from these isolates. Findings: We enrolled 69 patients with Kpn BSI. Common OPS serotypes accounted for 57/69 (83%) of infections. OPS was highly immunogenic in patients with Kpn BSI, and peak OPS-IgG antibody responses in patients were 10 to 30-fold higher than antibody levels detected in healthy controls, depending on the serotype. There was significant cross-reactivity among structurally similar OPS subtypes, including the O1v1/O1v2, O2v1/O2v2 and O3/O3b subtypes. Physiological amounts of capsule produced by both hyperencapsulated and non-hyperencapsulated Kpn significantly inhibited OPS-targeted antibody binding and function. Interpretation: OPS was highly immunogenic in patients with Kpn BSI, supporting its potential as a candidate vaccine antigen. The strong cross-reactivity observed between similar OPS subtypes in humans with Kpn BSI suggests that it may not be necessary to include all subtypes in an OPS-based vaccine. However, these observations are tempered by the fact that capsule production, even in non-highly encapsulated strains, has the potential to interfere with OPS antibody binding. This may limit the effectiveness of vaccines that exclusively target OPS. Funding: National Institute of Allergy and Infectious Diseases at the National Institutes of Health. Research in Context: Evidence before this study: Despite the potential of O-specific polysaccharide (OPS) as a vaccine antigen against Klebsiella pneumoniae (Kpn), the immunogenicity of OPS in humans remains largely unstudied, creating a significant knowledge gap with regard to vaccine development. A search of PubMed for publications up to March 18, 2024, using the terms " Klebsiella pneumoniae " and "O-specific polysaccharide" or "O-antigen" or "lipopolysaccharide" revealed no prior studies addressing OPS antibody responses in humans with Kpn bloodstream infections (BSI). One prior study 1 evaluated antibody response to a single lipopolysaccharide (which contains one subtype of OPS) in humans with invasive Kpn infection; however, in this study OPS typing of the infecting strains and target antigen were not described. Added value of this study: Our investigation into OPS immunogenicity in a human cohort marks a significant advance. Analyzing plasma antibody responses in 69 patients with Kpn BSI, we found OPS to be broadly immunogenic across all the types and subtypes examined, and there was significant cross-reactivity among structurally related OPS antigens. We also demonstrated that Kpn capsule production inhibit OPS antibody binding and the activation of complement on the bacterial surface, even in classical Kpn strains expressing lower levels of capsule.Implications of all the available evidence: While the immunogenicity and broad cross-reactivity of OPS in humans with Kpn BSI suggests it is a promising vaccine candidate, the obstruction of OPS antibody binding and engagement by physiologic levels of Kpn capsule underscores the potential limitations of an exclusively OPS-antigen based vaccine for Kpn. Our study provides insights for the strategic development of vaccines aimed at combating Kpn infections, an important antimicrobial resistant pathogen.

3.
ACS Nano ; 18(2): 1371-1380, 2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38060408

RESUMEN

Respiratory masks are the primary and most effective means of protecting individuals from airborne hazards such as droplets and particulate matter during public engagements. However, conventional electrostatically charged melt-blown microfiber masks typically require thick and dense membranes to achieve high filtration efficiency, which in turn cause a significant pressure drop and reduce breathability. In this study, we have developed a multielectrospinning system to address this issue by manipulating the pore structure of nanofiber networks, including the use of uniaxially aligned nanofibers created via an electric-field-guided electrospinning apparatus. In contrast to the common randomly collected microfiber membranes, partially aligned dual-nanofiber membranes, which are fabricated via electrospinning of a random 150 nm nanofiber base layer and a uniaxially aligned 450 nm nanofiber spacer layer on a roll-to-roll collector, offer an efficient way to modulate nanofiber membrane pore structures. Notably, the dual-nanofiber configuration with submicron pore structure exhibits increased fiber density and decreased volume density, resulting in an enhanced filtration efficiency of over 97% and a 50% reduction in pressure drop. This leads to the highest quality factor of 0.0781. Moreover, the submicron pore structure within the nanofiber networks introduces an additional sieving filtration mechanism, ensuring superior filtration efficiency under highly humid conditions and even after washing with a 70% ethanol solution. The nanofiber mask provides a sustainable solution for safeguarding the human respiratory system, as it effectively filters and inactivates human coronaviruses while utilizing 130 times fewer polymeric materials than melt-blown filters. This reusability of our filters and their minimum usage of polymeric materials would significantly reduce plastic waste for a sustainable global society.


Asunto(s)
Filtros de Aire , Nanofibras , Humanos , Nanofibras/química , Filtración , Polímeros
4.
Clin Infect Dis ; 78(1): 31-39, 2024 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-37633257

RESUMEN

BACKGROUND: The clinical and microbial factors associated with Klebsiella pneumoniae bloodstream infections (BSIs) are not well characterized. Prior studies have focused on highly resistant or hypervirulent isolates, limiting our understanding of K. pneumoniae strains that commonly cause BSI. We performed a record review and whole-genome sequencing to investigate the clinical characteristics, bacterial diversity, determinants of antimicrobial resistance, and risk factors for in-hospital death in a cohort of patients with K. pneumoniae BSI. METHODS: We identified 562 patients at Massachusetts General Hospital with K. pneumoniae BSIs between 2016 and 2022. We collected data on comorbid conditions, infection source, clinical outcomes, and antibiotic resistance and performed whole-genome sequencing on 108 sequential BSI isolates from 2021 to 2022. RESULTS: Intra-abdominal infection was the most common source of infection accounting for 34% of all BSIs. A respiratory tract source accounted for 6% of BSIs but was associated with a higher in-hospital mortality rate (adjusted odds ratio, 5.4 [95% confidence interval, 2.2-12.8]; P < .001 for comparison with other sources). Resistance to the first antibiotic prescribed was also associated with a higher risk of death (adjusted odds ratio, 5.2 [95% confidence interval, 2.2-12.4]; P < .001). BSI isolates were genetically diverse, and no clusters of epidemiologically and genetically linked cases were observed. Virulence factors associated with invasiveness were observed at a low prevalence, although an unexpected association between O-antigen type and the source of infection was found. CONCLUSIONS: These observations demonstrate the versatility of K. pneumoniae as an opportunistic pathogen and highlight the need for new approaches for surveillance and the rapid identification of patients with invasive antimicrobial-resistant K. pneumoniae infection.


Asunto(s)
Bacteriemia , Infección Hospitalaria , Infecciones por Klebsiella , Sepsis , Humanos , Klebsiella pneumoniae , Infección Hospitalaria/epidemiología , Mortalidad Hospitalaria , Bacteriemia/microbiología , Infecciones por Klebsiella/microbiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Sepsis/tratamiento farmacológico , Genómica
5.
Immune Netw ; 23(4): e31, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37670809

RESUMEN

Evidence suggests that the human respiratory tract, as with the gastrointestinal tract, has evolved to its current state in association with commensal microbes. However, little is known about how the airway microbiome affects the development of airway immune system. Here, we uncover a previously unidentified mode of interaction between host airway immunity and a unique strain (AIT01) of Staphylococcus epidermidis, a predominant species of the nasal microbiome. Intranasal administration of AIT01 increased the population of neutrophils and monocytes in mouse lungs. The recruitment of these immune cells resulted in the protection of the murine host against infection by Pseudomonas aeruginosa, a pathogenic bacterium. Interestingly, an AIT01-secreted protein identified as GAPDH, a well-known bacterial moonlighting protein, mediated this protective effect. Intranasal delivery of the purified GAPDH conferred significant resistance against other Gram-negative pathogens (Klebsiella pneumoniae and Acinetobacter baumannii) and influenza A virus. Our findings demonstrate the potential of a native nasal microbe and its secretory protein to enhance innate immune defense against airway infections. These results offer a promising preventive measure, particularly relevant in the context of global pandemics.

6.
PLoS One ; 17(8): e0271760, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35947557

RESUMEN

During the COVID-19 pandemic, analyses on global data have not reached unanimous consensus on whether warmer and humid weather curbs the spread of the SARS-CoV-2 virus. We conjectured that this lack of consensus is due to the discrepancy between global environmental data such as temperature and humidity being collected outdoors, while most infections have been reported to occur indoors, where conditions can be different. Thus, we have methodologically investigated the effect of temperature and relative humidity on the spread of expired respiratory droplets from the mouth, which are assumed to be the main cause of most short-range infections. Calculating the trajectory of individual droplets using an experimentally validated evaporation model, the final height and distance of the evaporated droplets is obtained, and then correlated with global COVID-19 spread. Increase in indoor humidity is associated with reduction in COVID-19 spread, while temperature has no statistically significant effect.


Asunto(s)
COVID-19 , COVID-19/epidemiología , Humanos , Humedad , Pandemias , SARS-CoV-2 , Temperatura
7.
Chem Eng J ; 444: 136460, 2022 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-35463870

RESUMEN

Most respiratory masks are made of fabrics, which only capture the infectious virus carriers into the matrix. However, these contagious viruses stay active for a long duration (∼7 days) within the fabric matrix possibly inducing post-contact transmissions. Moreover, conventional masks are vulnerable to bacterial growth with prolonged exposure to exhaled breaths. Herein, we combined violacein, a naturally-occurring antimicrobial agent, with porous nanofiber membranes to develop a series of functional filters that autonomously sterilizes viruses and bacteria. The violacein-embedded membrane inactivates viruses within 4 h (99.532 % reduction for influenza and 99.999 % for human coronavirus) and bacteria within 2 h (75.5 % reduction). Besides, its nanofiber structure physically filters out the nanoscale (<0.8 µm) and micron-scale (0.8 µm - 3 µm) particulates, providing high filtration efficiencies (99.7 % and 100 % for PM 1.0 and PM 10, respectively) with long-term stability (for 25 days). In addition, violacein provides additional UV-resistant property, which protects the skin from sunlight. The violacein-embedded membrane not only proved the sterile efficacy of microbe extracted pigments for biomedical products but also provided insights to advance the personal protective equipment (PPE) to fight against contagious pathogens.

8.
PLoS Pathog ; 17(6): e1009681, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-34161396

RESUMEN

Pseudomonas aeruginosa (PA) is an opportunistic pathogen that causes diverse human infections including chronic airway infection in patients with cystic fibrosis (CF). Comparing the genomes of CF and non-CF PA isolates has great potential to identify the genetic basis of pathogenicity. To gain a deeper understanding of PA adaptation in CF airways, we performed a genome-wide association study (GWAS) on 1,001 PA genomes. Genetic variations identified among CF isolates were categorized into (i) alterations in protein-coding regions, either large- or small-scale, and (ii) polymorphic variation in intergenic regions. We introduced each CF-associated genetic alteration into the genome of PAO1, a prototype PA strain, and validated the outcomes experimentally. Loci readily mutated among CF isolates included genes encoding a probable sulfatase, a probable TonB-dependent receptor (PA2332~PA2336), L-cystine transporter (YecS, PA0313), and a probable transcriptional regulator (PA5438). A promoter region of a heme/hemoglobin uptake outer membrane receptor (PhuR, PA4710) was also different between the CF and non-CF isolate groups. Our analysis highlights ways in which the PA genome evolves to survive and persist within the context of chronic CF infection.


Asunto(s)
Fibrosis Quística/microbiología , Infecciones por Pseudomonas/genética , Pseudomonas aeruginosa/genética , Variación Genética , Estudio de Asociación del Genoma Completo , Humanos
9.
J Biol Chem ; 296: 100576, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33757766

RESUMEN

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen whose virulence is dependent on quorum sensing (QS). DksA1, an RNA polymerase-binding transcriptional regulator, plays a role in determining a number of phenotypes, including QS-mediated virulence. We therefore envisioned that DksA1 inhibitors may help to control P. aeruginosa infection. Here, we screened a library of 6970 chemical compounds and identified two compounds (henceforth termed Dkstatins) that specifically suppressed DksA1 activity. Treatment with these two compounds also substantially decreased the production of elastase and pyocyanin, dominant virulence determinants of P. aeruginosa, and protected murine hosts from lethal infection from a prototype strain of P. aeruginosa, PAO1. The Dkstatins also suppressed production of homoserine lactone (HSL)-based autoinducers that activate P. aeruginosa QS. The level of 3-oxo-C12-HSL produced by Dkstatin-treated wildtype PAO1 closely resembled that of the ΔdksA1 mutant. RNA-Seq analysis showed that transcription levels of QS- and virulence-associated genes were markedly reduced in Dkstatin-treated PAO1 cells, indicating that Dkstatin-mediated suppression occurs at the transcriptional level. Importantly, Dkstatins increased the antibiotic susceptibilities of PAO1, particularly to protein synthesis inhibitors, such as tobramycin and tetracycline. Co-immunoprecipitation assays demonstrated that these Dkstatins interfered with DksA1 binding to the ß subunit of RNA polymerase, pointing to a potential mechanism of action. Collectively, our results illustrate that inhibition of P. aeruginosa QS may be achieved via DksA1 inhibitors and that Dkstatins may serve as potential lead compounds to control infection.


Asunto(s)
Antibacterianos/farmacología , Proteínas Bacterianas/antagonistas & inhibidores , Secuencia Conservada , Pseudomonas aeruginosa/citología , Pseudomonas aeruginosa/efectos de los fármacos , Percepción de Quorum/efectos de los fármacos , Animales , Proteínas Bacterianas/química , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Línea Celular , Ratones , Mutación , Pseudomonas aeruginosa/metabolismo , Pseudomonas aeruginosa/patogenicidad , Virulencia/efectos de los fármacos
10.
J Biol Eng ; 15(1): 9, 2021 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-33676548

RESUMEN

Short-chain fatty acids, especially butyrate, play beneficial roles in sustaining gastrointestinal health. However, due to limitations associated with direct consumption of butyrate, there has been interest in using prodrugs of butyrate. Tributyrin (TB), a triglyceride composed of three butyrate molecules and a glycerol, is a well-studied precursor of butyrate. We screened a metagenome library consisting of 5760 bacterial artificial chromosome clones, with DNA inserts originating from mouse microbiomes, and identified two clones that efficiently hydrolyse TB into butyrate. Nucleotide sequence analysis indicated that inserts in these two clones are derived from unknown microbes. BLASTp analysis, however, revealed that each insert contains a gene homologous to acetylesterase or esterase genes, from Clostridium spp. and Bacteroides spp., respectively. Predicted structures of these two proteins both contain serine-histidine-aspartate catalytic triad, highly conserved in the family of esterases. Escherichia coli host expressing each of the two candidate genes invariably produced greater amounts of butyrate in the presence of TB. Importantly, administration of TB together with cloned E. coli cells alleviated inflammatory symptoms in a mouse model of acute colitis. Based on these results, we established an efficient on-site and real-time butyrate production system that releases butyrate in a controlled manner inside the intestine.

11.
ACS Nano ; 14(12): 16907-16918, 2020 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-33275412

RESUMEN

The colorimetric gas sensor offers an opportunity for the simple and rapid detection of toxic gaseous substances based on visually discernible changes in the color of the sensing material. In particular, the accurate detection of trace amounts of certain biomarkers in a patient's breath provides substantial clues regarding specific diseases, for example, hydrogen sulfide (H2S) for halitosis and ammonia (NH3) for kidney disorder. However, conventional colorimetric sensors often lack the sensitivity, selectivity, detection limit, and mass-productivity, impeding their commercialization. Herein, we report an inexpensive route for the meter-scale synthesis of a colorimetric sensor based on a composite nanofiber yarn that is chemically functionalized with an ionic liquid as an effective H2S adsorbent and lead acetate as a colorimetric dye. As an eye-readable and weavable sensing platform, the single-strand yarn exhibits enhanced sensitivity supported by its high surface area and well-developed porosity to detect the breath biomarker (1 ppm of H2S). Alternatively, the yarn loaded with lead iodide dyes could reversibly detect NH3 gas molecules in the ppm-level, demonstrating the facile extensibility. Finally, we demonstrated that the freestanding yarns could be sewn into patterned textiles for the fabrication of a wearable toxic gas alarm system with a visual output.

12.
ACS Nano ; 14(9): 12173-12183, 2020 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-32880440

RESUMEN

The cost-effective direct writing of polymer nanofibers (NFs) has garnered considerable research attention as a compelling one-pot strategy for obtaining key building blocks of electrochemical and optical devices. Among the promising applications, the changes in optical response from external stimuli such as mechanical deformation and changes in the thermal environment are of great significance for emerging applications in smart windows, privacy protection, aesthetics, artificial skin, and camouflage. Herein, we propose a rational design for the mass production of customized NFs through the development of focused electric-field polymer writing (FEPW) coupled with the roll-to-roll technique. As a proof of key applications, we demonstrate multistimuli-responsive (mechano- and thermochromism) membranes with an exceptional production scale (over 300 cm2). Specifically, the membranes consist of periodically aligned ultrathin (∼60 nm) alumina nanotubes inserted in the elastomers. We performed a two-phase finite element analysis of the unit cells to verify the underlying physics of light scattering at heterogeneous interfaces of the strain-induced air gaps. By adding thermochromic dye during the FEPW, the optical modulation of transmittance change (∼83% to 37% at visible wavelength) was successfully extended to high-contrast thermal-dependent coloration.

13.
Sci Rep ; 9(1): 487, 2019 01 24.
Artículo en Inglés | MEDLINE | ID: mdl-30679735

RESUMEN

Pseudomonas aeruginosa displays intrinsic resistance to many antibiotics and known to acquire actively genetic mutations for further resistance. In this study, we attempted to understand genomic and transcriptomic landscapes of P. aeruginosa clinical isolates that are highly resistant to multiple antibiotics. We also aimed to reveal a mode of antibiotic resistance by elucidating transcriptional response of genes conferring antibiotic resistance. To this end, we sequenced the whole genomes and profiled genome-wide RNA transcripts of three different multi-drug resistant (MDR) clinical isolates that are phylogenetically distant from one another. Multi-layered genome comparisons with genomes of antibiotic-susceptible P. aeruginosa strains and 70 other antibiotic-resistance strains revealed both well-characterized conserved gene mutations and distinct distribution of antibiotic-resistant genes (ARGs) among strains. Transcriptions of genes involved in quorum sensing and type VI secretion systems were invariably downregulated in the MDR strains. Virulence-associated phenotypes were further examined and results indicate that our MDR strains are clearly avirulent. Transcriptions of 64 genes, logically selected to be related with antibiotic resistance in MDR strains, were active under normal growth conditions and remained unchanged during antibiotic treatment. These results propose that antibiotic resistance is achieved by a "constitutive" response scheme, where ARGs are actively expressed even in the absence of antibiotic stress, rather than a "reactive" response. Bacterial responses explored at the transcriptomic level in conjunction with their genome repertoires provided novel insights into (i) the virulence-associated phenotypes and (ii) a mode of antibiotic resistance in MDR P. aeruginosa strains.


Asunto(s)
Farmacorresistencia Bacteriana Múltiple , Regulación Bacteriana de la Expresión Génica , Infecciones por Pseudomonas , Pseudomonas aeruginosa , Transcripción Genética , Factores de Virulencia , Animales , Humanos , Ratones , Ratones Endogámicos BALB C , Infecciones por Pseudomonas/genética , Infecciones por Pseudomonas/metabolismo , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo , Pseudomonas aeruginosa/patogenicidad , Factores de Virulencia/biosíntesis , Factores de Virulencia/genética
14.
ACS Appl Mater Interfaces ; 10(23): 19957-19963, 2018 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-29779365

RESUMEN

Here, we propose heterogeneous nucleation-assisted hierarchical growth of metal-organic frameworks (MOFs) for efficient particulate matter (PM) removal. The assembly of two-dimensional (2D) Zn-based zeolite imidazole frameworks (2D-ZIF-L) in deionized water over a period of time produced hierarchical ZIF-L (H-ZIF-L) on hydrophilic substrates. During the assembly, the second nucleation and growth of ZIF-L occurred on the surface of the first ZIF-L, leading to the formation of flowerlike H-ZIF-L on the substrate. The flowerlike H-ZIF-L was easily synthesized on various substrates, namely, glass, polyurethane three-dimensional foam, nylon microfibers, and nonwoven fabrics. We demonstrated H-ZIF-L-assembled polypropylene microfibers as a washable membrane filter with highly efficient PM removal property (92.5 ± 0.8% for PM2.5 and 99.5 ± 0.2% for PM10), low pressure drop (10.5 Pa at 25 L min-1), long-term stability, and superior recyclability. These outstanding particle filtering properties are mainly attributed to the unique structure of the 2D-shaped H-ZIF-L, which is tightly anchored on individual fibers comprising the membrane.

15.
Artículo en Inglés | MEDLINE | ID: mdl-27900286

RESUMEN

Vibrio cholerae, a Gram-negative bacterium, is the causative agent of pandemic cholera. Previous studies have shown that the survival of the seventh pandemic El Tor biotype V. cholerae strain N16961 requires production of acetoin in a glucose-rich environment. The production of acetoin, a neutral fermentation end-product, allows V. cholerae to metabolize glucose without a pH drop, which is mediated by the production of organic acid. This finding suggests that inhibition of acetoin fermentation can result in V. cholerae elimination by causing a pH imbalance under glucose-rich conditions. Here, we developed a simple high-throughput screening method and identified an inducer of medium acidification (iMAC). Of 8364 compounds screened, we identified one chemical, 5-(4-chloro-2-nitrobenzoyl)-6-hydroxy-1,3-dimethylpyrimidine-2,4(1H,3H)-dione, that successfully killed glucose-metabolizing N16961 by inducing acidic stress. When N16961 was grown with abundant glucose in the presence of iMAC, acetoin production was completely suppressed and concomitant accumulation of lactate and acetate was observed. Using a beta-galactosidase activity assay with a single-copy palsD::lacZ reporter fusion, we show that that iMAC likely inhibits acetoin production at the transcriptional level. Thin-layer chromatography revealed that iMAC causes a significantly reduced accumulation of intracellular (p)ppGpp, a bacterial stringent response alarmone known to positively regulate acetoin production. In vivo bacterial colonization and fluid accumulation were also markedly decreased after iMAC treatment. Finally, we demonstrate iMAC-induced bacterial killing for 22 different V. cholerae strains belonging to diverse serotypes. Together, our results suggest that iMAC, acting as a metabolic modulator, has strong potential as a novel antibacterial agent for treatment against cholera.


Asunto(s)
Antibacterianos/farmacología , Metabolismo de los Hidratos de Carbono/efectos de los fármacos , Glucosa/metabolismo , Vibrio cholerae/efectos de los fármacos , Vibrio cholerae/crecimiento & desarrollo , Vibrio cholerae/metabolismo , Acetoína/metabolismo , Ácidos/metabolismo , Animales , Antibacterianos/química , Metabolismo de los Hidratos de Carbono/genética , Cólera/tratamiento farmacológico , Cólera/microbiología , Cromatografía en Capa Delgada , Pruebas Inmunológicas de Citotoxicidad , Modelos Animales de Enfermedad , Escherichia coli/genética , Fermentación , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Ensayos Analíticos de Alto Rendimiento/métodos , Concentración de Iones de Hidrógeno , Ratones , Viabilidad Microbiana , Microscopía Electrónica de Rastreo , Vibrio/clasificación , Vibrio cholerae/genética , beta-Galactosidasa/análisis
16.
Nanotechnology ; 27(43): 435301, 2016 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-27651316

RESUMEN

Aligned nanofiber arrays and mats were fabricated with an electrospinning process by manipulating the electric field. The electric field was modified by insulating blocks (IBs) that were installed between the nozzle and the substrate as guiding elements to control the trajectory of the electrospinning jet flow. Simulation results showed that the electric field was deformed near the IBs, resulting in confinement of the electrospinning jet between the blocks. The balance of the electric field in the vertical direction and the repulsive force by space charges in the confined electrified jet stream was attributed to the aligned motion of the jet. Aligned arrays of 200 nm thick polyethylene oxide nanofibers were obtained, exhibiting wave-shaped and cross patterns as well as rectilinear patterns. In addition, 40 µm thick quasi-aligned carbon-nanofiber mats with anisotropic electrical property were also attained by this method.

17.
Int J Environ Res Public Health ; 11(3): 2865-75, 2014 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-24619120

RESUMEN

This study aimed to quantify the effect of duration time of a nuclear accident on the radiation dose of a densely populated area and the resulting acute health effects. In the case of nuclear accidents, the total emissions of radioactive materials can be classified into several categories. Therefore, the release information is very important for the assessment of risk to the public. We confirmed that when the duration time of the emissions are prolonged to 7 hours, the concentrations of radioactive substances in the ambient air are reduced by 50% compared to that when the duration time of emission is one hour. This means that the risk evaluation using only the first wind direction of an accident is very conservative, so it has to be used as a screening level for the risk assessment. Furthermore, it is judged that the proper control of the emission time of a nuclear accident can minimize the health effects on residents.


Asunto(s)
Contaminantes Radiactivos del Aire/efectos adversos , Contaminación Radiactiva del Aire/efectos adversos , Traumatismos por Radiación/etiología , Liberación de Radiactividad Peligrosa , Humanos , Modelos Estadísticos , Dosis de Radiación , Medición de Riesgo , Factores de Tiempo
18.
Appl Radiat Isot ; 79: 1-4, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23711992

RESUMEN

This paper specifically discusses a radiological risk assessment due to RDDs (Radiological Dispersion Devices) containing Cs-137 in the metropolitan area of Seoul, South Korea. The comparison of an effective dose caused by airborne plume and deposited Cs-137 is performed with and without consideration of the wind direction. When the dose is computed conservatively, an effective dose is around twice that of a dose computed realistically. Monte Carlo simulations showed that the 95% confidence interval for morbidity was 2.40×10(-5) to 8.55×10(-5), and mortality was 3.53×10(-5) to 1.25×10(-4).


Asunto(s)
Guerra Nuclear , Terrorismo , Población Urbana , Humanos , Método de Montecarlo , República de Corea , Medición de Riesgo
19.
Radiat Prot Dosimetry ; 154(4): 430-8, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23108599

RESUMEN

The characteristics of atmospheric dispersion considering the building effects in the Wolsung nuclear site in Korea were studied using ISC-PRIME and ARCON96 models. The maximum 2-h average atmospheric dispersion factor (ADF) was six times larger when the building geometry was considered in ISC-PRIME and two times larger in the exclusion area boundary. Owing to different adjustments for wind speed by the stability class, the ADFs calculated using ARCON96 were smaller than those calculated using ISC-PRIME. Strategies for locating buildings need to be considered to maximise dispersion when planning for constructing several reactors and accessory buildings at the Wolsung nuclear site.


Asunto(s)
Contaminantes Atmosféricos/química , Contaminación Radiactiva del Aire , Monitoreo del Ambiente , Plantas de Energía Nuclear , Características de la Residencia , Humanos , Modelos Teóricos , Viento
20.
Nanoscale Res Lett ; 7: 52, 2012 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-22221446

RESUMEN

Electrospray process was developed for organic layer deposition onto polymer organic light-emitting diode [PLED] devices in this work. An electrospray can be used to produce nanometer-scale thin films by electric repulsion of microscale fine droplets. PLED devices made by an electrospray process were compared with spin-coated ones. The PLED device fabricated by the electrospray process showed maximum current efficiency of 24 cd/A, which was comparable with that of the spin-coating process. The electrospray process required a higher concentration of hole and electron transport materials in the inks than spin-coating processes to achieve PLED maximum performance. Photoluminescence [PL] at 407 nm was observed using electrosprayed poly(N-vinyl carbazole) films, whereas a peak at 410 nm was observed with the spin-coated ones. Similar difference in peak position was observed between aromatic and nonaromatic solvents in the spin-coating process. PLED devices made by the electrospray process showed lower current density than that of spin-coated ones. The PL peak shift and reduced current of electrosprayed films can therefore be attributed to the conformation of the polymer.

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