Search Results (10)

Neonatal Meningitis-causing Escherichia coli (NMEC) is the leading cause of neonatal meningitis and exhibits remarkable adaptability to diverse host environments. Understanding its transcriptional responses across different host niches is crucial for deciphering pathogenesis and identifying potential therapeutic targets. We performed a comparative transcriptomic analysis of NMEC RS218, the prototype strain of NMEC, under four distinct host-mimicking conditions: colonic fluid (CF), serum (S), human brain endothelial cells (HBECs), and cerebrospinal fluid (CSF). Differential gene expression analysis was conducted to assess metabolic shifts, virulence factor regulation, and niche-specific adaptation strategies, in which RS218 demonstrated niche-specific transcriptional reprogramming. In CF, genes associated with biofilm formation, motility, efflux pumps, and cell division regulation were upregulated, aiding gut colonization. The serum environment triggered the expression of siderophore-mediated iron acquisition, enterobactin biosynthesis, and heme utilization genes, facilitating immune evasion and bacterial persistence. In HBECs, NMEC upregulated genes linked to nucleoside metabolism, membrane remodeling, pilus organization, and blood–brain barrier (BBB) traversal. In CSF, genes related to oxidative stress resistance, chemotaxis, DNA repair, biofilm formation, and amino acid biosynthesis were enriched, reflecting NMEC’s adaptive mechanisms for survival under nutrient-depleted conditions. Energy-intensive pathways were consistently downregulated across all niches, highlighting the need for an energy conservation strategy. This study provides novel insights into NMEC’s adaptive strategies across different host environments, emphasizing its metabolic flexibility, virulence regulation, and immune evasion mechanisms, offering potential targets for therapeutic intervention. Full article

Bacterial meningitis is a devastating disease occurring worldwide, with up to half of survivors left with permanent neurological sequelae. Neonatal meningitis-causing Escherichia coli (NMEC) is the most common Gram-negative bacillary organism that causes meningitis, particularly during the neonatal period. Here, RNA-seq transcriptional profiles of microglia in response to NMEC infection show that microglia are activated to produce inflammatory factors. In addition, we found that the secretion of inflammatory factors is a double-edged sword that promotes polymorphonuclear neutrophil (PMN) recruitment to the brain to clear the pathogens but, at the same time, induces neuronal damage, which may be related to the neurological sequelae. New neuroprotective therapeutic strategies must be developed for the treatment of acute bacterial meningitis. We found that transforming growth factor-β (TGF-β) may be a strong candidate in the treatment of acute bacterial meningitis, as it shows a therapeutic effect on bacterial-meningitis-induced brain damage. Prevention of disease and early initiation of the appropriate treatment in patients with suspected or proven bacterial meningitis are the key factors in reducing morbidity and mortality. Novel antibiotic and adjuvant treatment strategies must be developed, and the main goal for new therapies will be dampening the inflammatory response. Based on this view, our findings may help develop novel strategies for bacterial meningitis treatment. Full article

Avian pathogenic Escherichia coli (APEC) is an important member of extraintestinal pathogenic Escherichia coli (ExPEC). It shares similar pathogenic strategies with neonatal meningitis E. coli (NMEC) and may threaten human health due to its potential zoonosis. RyhB is a small non-coding RNA that regulates iron homeostasis in E. coli. However, it is unclear whether RyhB regulates meningitis occurrence. To investigate the function of RyhB in the development of meningitis, we constructed the deletion mutant APEC XM∆ryhB and the complemented mutant APEC XM∆ryhB/pryhB, established a mouse meningitis model and evaluated the role of RyhB in virulence of APEC. The results showed that the deletion of ryhB decreased biofilm formation, adhesion to the brain microvascular endothelial cell line bEnd.3 and serum resistance. RNA-seq data showed that the expression of multiple virulence-related genes changed in the ryhB deletion mutant in the presence of duck serum. Deletion of ryhB reduced the clinical symptoms of mice, such as opisthotonus, diarrhea and neurological signs, when challenged with APEC. Compared with the mice infected with the wild-type APEC, fewer histopathological lesions were observed in the brain of mice infected with the ryhB deletion mutant APEC XM∆ryhB. The bacterial loads in the tissues and the relative expression of cytokines (IL-1β, IL-6, and TNF-α) in the brain significantly decreased when challenged with the APEC XM∆ryhB. The expressions of tight junction proteins (claudin-5, occludin and ZO-1) were not reduced in the brain of mice infected with APEC XM∆ryhB; that is, the blood-brain barrier permeability of mice was not significantly damaged. In conclusion, RyhB contributes to the pathogenicity of APEC XM in the meningitis-causing process by promoting biofilm formation, adhesion to endothelial cells, serum resistance and virulence-related genes expression. Full article

This article presents an assessment of sustainability conducted post the opening of the National Museum of Egyptian Civilization (NMEC), which underwent vast development that had significant impacts, not only on the global level but also on the international attention towards Egypt’s great civilization. The study investigates the impact of the NMEC’s environmental, social, and economic sustainability and cultural value. Both qualitative and quantitative approaches were adopted. The qualitative includes a preliminary study followed by site visits for collecting data and mapping the four sustainability pillars: environmental, social, economic, and cultural. The quantitative approach has been conducted by exploiting 33 indicators to measure five sustainability dimensions in addition to the UNESCO 15 Thematic Indicators for Culture in the 2030 Agenda; the impact of NMEC on social media using the data scraping technique exploiting GitHub. Energy audit results illustrate that the total annual energy consumption is 491,376.00 kWh (79% in the ground fl. & 21% in the Mummies fl.), as well as 19.98 kWh/m² (Gr. fl.) and 144 kWh/m² (Mummies fl.); the first matches RIBA’s benchmark for museums, well below the ranking ‘Good’ (50 kWh/m²). Social sustainability impacts indicate that the word count’s effect on social media is 27%, 31%, and 42% on Facebook, Instagram, and Twitter, respectively, while the number of followers is 92%, 7%, and 1%. On Google, it is 1275 and ranks 4.7, whereas the number of posts is 231, 350, and 258. Economic sustainability assessment has been addressed by calculating the revenues throughout one year since the grand opening, and the total revenues amount to USD 2,794,047. The cultural sustainability assessment showed a positive response to the evaluation recorded for 9 out of 15 indicators. The sustainability assessment of the NMEC plays a key role in assuring livable and regenerative cities. Full article

Avian pathogenic Escherichia coli (APEC) is an important extra-intestinal pathogenic E. coli (ExPEC), which often causes systemic infection in poultry and causes great economic loss to the breeding industry. In addition, as a major source of human ExPEC infection, the potential zoonotic risk of APEC has been an ongoing concern. Previous studies have pointed out that APEC is a potential zoonotic pathogen, which has high homology with human pathogenic E. coli such as uro-pathogenic E. coli (UPEC) and neonatal meningitis E. coli (NMEC), shares multiple virulence factors and can cause mammalian diseases. Previous studies have reported that O18 and O78 could cause different degrees of meningitis in neonatal rats, and different serotypes had different degrees of zoonotic risk. Here, we compared APEC DE205B (O2:K1) with NMEC RS218 (O18:K1:H7) by phylogenetic analysis and virulence gene identification to analyze the potential risk of DE205B in zoonotic diseases. We found that DE205B possessed a variety of virulence factors associated with meningitis and, through phylogenetic analysis, had high homology with RS218. DE205B could colonize the cerebrospinal fluid (CSF) of rats, and cause meningitis and nerve damage. Symptoms and pathological changes in the brain were similar to RS218. In addition, we found that DE205B had a complete T6SS, of which Hcp protein was its important structural protein. Hcp1 induced cytoskeleton rearrangement in human brain microvascular endothelial cells (HBMECs), and Hcp2 was mainly involved in the invasion of DE205B in vitro. In the meningitis model of rats, deletion of hcp2 gene reduced survival in the blood and the brain invasiveness of DE205B. Compared with WT group, Δhcp2 group induced lower inflammation and neutrophils infiltration in brain tissue, alleviating the process of meningitis. Together, these results suggested that APEC DE205B had close genetic similarities to NMEC RS218, and a similar mechanism in causing meningitis and being a risk for zoonosis. This APEC serotype provided a basis for zoonotic research. Full article

We examine the energy use impacts of energy efficiency and solar PV projects financed by residential property assessed clean energy (R-PACE) programs in California. We leverage household-level interval meter data to apply normalized metered energy consumption (NMEC) methods at significant scale—more than 25,000 electric meters and more than 15,000 gas meters. We develop a comparison group to account for non-project-related changes in usage. The projects include homes that replaced existing HVAC equipment with higher-efficiency units and homes that installed central heating or air conditioning equipment for the first time. We have limited information on pre-project household equipment stock so we develop a method to infer new installations. We find that projects that installed energy efficiency technologies reduce electricity consumption by approximately 3% and gas consumption by approximately 3.5% on average. When we remove homes that installed new cooling and heating equipment for the first time, savings rise to approximately 5% for electricity and approximately 6% for gas. Given the California climate and the results of an existing study of similar California projects, these results are in line with expectations. Solar PV projects produce electricity that offsets approximately 69% of household electricity consumption on average. We estimate that California R-PACE projects installed through the end of 2019 produce annual reductions in grid-tied electricity consumption of 506 GWh (equivalent to the electricity consumption of approximately 74,000 California households) and gas consumption reductions of 2 million therms (equivalent to the gas consumption of approximately 4700 California households) in a typical weather year. Full article

Avian pathogenic Escherichia coli (APEC) causes colibacillosis in avian species, and recent reports have suggested APEC as a potential foodborne zoonotic pathogen. Herein, we discuss the virulence and pathogenesis factors of APEC, review the zoonotic potential, provide the current status of antibiotic resistance and progress in vaccine development, and summarize the alternative control measures being investigated. In addition to the known virulence factors, several other factors including quorum sensing system, secretion systems, two-component systems, transcriptional regulators, and genes associated with metabolism also contribute to APEC pathogenesis. The clear understanding of these factors will help in developing new effective treatments. The APEC isolates (particularly belonging to ST95 and ST131 or O1, O2, and O18) have genetic similarities and commonalities in virulence genes with human uropathogenic E. coli (UPEC) and neonatal meningitis E. coli (NMEC) and abilities to cause urinary tract infections and meningitis in humans. Therefore, the zoonotic potential of APEC cannot be undervalued. APEC resistance to almost all classes of antibiotics, including carbapenems, has been already reported. There is a need for an effective APEC vaccine that can provide protection against diverse APEC serotypes. Alternative therapies, especially the virulence inhibitors, can provide a novel solution with less likelihood of developing resistance. Full article

Although many developing countries use harvested rainwater (HRW) for drinking and other household purposes, its quality is seldom monitored. Continuous assessment of the microbial quality of HRW would ensure the safety of users of such water. The current study investigated the prevalence of pathogenic Escherichia coli strains and their antimicrobial resistance patterns in HRW tanks in the Eastern Cape, South Africa. Rainwater samples were collected weekly between June and September 2016 from 11 tanks in various areas of the province. Enumeration of E. coli was performed using the Colilert^®18/Quanti-Tray^® 2000 method. E. coli isolates were obtained and screened for their virulence potentials using polymerase chain reaction (PCR), and subsequently tested for antibiotic resistance using the disc-diffusion method against 11 antibiotics. The pathotype most detected was the neonatal meningitis E. coli (NMEC) (ibeA 28%) while pathotype enteroaggregative E. coli (EAEC) was not detected. The highest resistance of the E. coli isolates was observed against Cephalothin (76%). All tested pathotypes were susceptible to Gentamicin, and 52% demonstrated multiple-antibiotic resistance (MAR). The results of the current study are of public health concern since the use of untreated harvested rainwater for potable purposes may pose a risk of transmission of pathogenic and antimicrobial-resistant E. coli. Full article

The simultaneous occurrence of various types of defects in bearings makes their diagnosis more challenging owing to the resultant complexity of the constituent parts of the acoustic emission (AE) signals. To address this issue, a new approach is proposed in this paper for the detection of multiple combined faults in bearings. The proposed methodology uses a deep neural network (DNN) architecture to effectively diagnose the combined defects. The DNN structure is based on the stacked denoising autoencoder non-mutually exclusive classifier (NMEC) method for combined modes. The NMEC-DNN is trained using data for a single fault and it classifies both single faults and multiple combined faults. The results of experiments conducted on AE data collected through an experimental test-bed demonstrate that the DNN achieves good classification performance with a maximum accuracy of 95%. The proposed method is compared with a multi-class classifier based on support vector machines (SVMs). The NMEC-DNN yields better diagnostic performance in comparison to the multi-class classifier based on SVM. The NMEC-DNN reduces the number of necessary data collections and improves the bearing fault diagnosis performance. Full article

Pertussis toxin (PTx), the major virulence factor of the whooping cough-causing bacterial pathogen Bordetella pertussis, permeabilizes the blood–brain barrier (BBB) in vitro and in vivo. Breaking barriers might promote translocation of meningitis-causing bacteria across the BBB, thereby facilitating infection. PTx activates several host cell signaling pathways exploited by the neonatal meningitis-causing Escherichia coli K1-RS218 for invasion and translocation across the BBB. Here, we investigated whether PTx and E. coli K1-RS218 exert similar effects on MAPK p38, NF-κB activation and transcription of downstream targets in human cerebral endothelial TY10 cells using qRT-PCR, Western blotting, and ELISA in combination with specific inhibitors. PTx and E. coli K1-RS218 activate MAPK p38, but only E. coli K1-RS218 activates the NF-κB pathway. mRNA and protein levels of p38 and NF-κB downstream targets including IL-6, IL-8, CxCL-1, CxCL-2 and ICAM-1 were increased. The p38 specific inhibitor SB203590 blocked PTx-enhanced activity, whereas E. coli K1-RS218’s effects were inhibited by the NF-κB inhibitor Bay 11-7082. Further, we found that PTx enhances the adherence of human monocytic THP-1 cells to human cerebral endothelial TY10 cells, thereby contributing to enhanced translocation. These modulations of host cell signaling pathways by PTx and meningitis-causing E. coli support their contributions to pathogen and monocytic THP-1 cells translocation across the BBB. Full article