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Active surveillance and studying the virological features of avian-origin influenza viruses are essential for early warning and preparedness for the next potential pandemic. During our active surveillance of avian influenza viruses in wild birds in Egypt in the period 2014-2017, multiple reassortant low-pathogenic avian influenza H7N3 viruses were isolated. In this study, we investigated and compared the infectivity, pathogenicity, and transmission of four different constellation forms of Egyptian H7N3 viruses in chickens and mice and assessed the sensitivity of these viruses to different commercial antiviral drugs in vitro. Considerable variation in virus pathogenicity was observed in mice infected with different H7N3 viruses. The mortality rate ranged from 20 to 100% in infected mice. Infected chickens showed only ocular clinical signs at three days postinfection as well as systemic viral infection in different organs. Efficient virus replication and transmission in chickens was observed within each group, indicating that these subtypes can spread easily from wild birds to poultry without prior adaptation. Mutations in the viral proteins associated with antiviral drug resistance were not detected, and all strains were sensitive to the antiviral drugs tested. In conclusion, all of the viruses studied had the ability to infect mice and chickens. H7N3 viruses circulating among wild birds in Egypt could threaten poultry production and public health.
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Subtipo H7N3 del Virus de la Influenza A , Gripe Aviar , Animales , Ratones , Subtipo H7N3 del Virus de la Influenza A/genética , Pollos , Egipto/epidemiología , Antivirales/farmacología , Animales Salvajes , Aves de Corral , Virus Reordenados/genética , FilogeniaRESUMEN
BACKGROUND: Streptococcus agalactiae or group B Streptococcus (GBS) asymptomatically colonizes the genitourinary tracts of up to 30% of pregnant women. Globally, GBS is an important cause of neonatal morbidity and mortality. GBS has recently been linked to adverse pregnancy outcomes. The potential interactions between GBS and the vaginal microbiome composition remain poorly understood. In addition, little is known about the vaginal microbiota of pregnant Egyptian women. RESULTS: Using V3-V4 16S rRNA next-generation sequencing, we examined the vaginal microbiome in GBS culture-positive pregnant women (22) and GBS culture-negative pregnant women (22) during the third trimester in Ismailia, Egypt. According to the alpha-diversity indices, the vaginal microbiome of pregnant GBS culture-positive women was significantly more diverse and less homogenous. The composition of the vaginal microbiome differed significantly based on beta-diversity between GBS culture-positive and culture-negative women. The phylum Firmicutes and the family Lactobacillaceae were significantly more abundant in GBS-negative colonizers. In contrast, the phyla Actinobacteria, Tenericutes, and Proteobacteria and the families Bifidobacteriaceae, Mycoplasmataceae, Streptococcaceae, Corynebacteriaceae, Staphylococcaceae, and Peptostreptococcaceae were significantly more abundant in GBS culture-positive colonizers. On the genus and species levels, Lactobacillus was the only genus detected with significantly higher relative abundance in GBS culture-negative status (88%), and L. iners was the significantly most abundant species. Conversely, GBS-positive carriers exhibited a significant decrease in Lactobacillus abundance (56%). In GBS-positive colonizers, the relative abundance of the genera Ureaplasma, Gardnerella, Streptococcus, Corynebacterium, Staphylococcus, and Peptostreptococcus and the species Peptostreptococcus anaerobius was significantly higher. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to the metabolism of cofactors and vitamins, phosphatidylinositol signaling system, peroxisome, host immune system pathways, and host endocrine system were exclusively enriched among GBS culture-positive microbial communities. However, lipid metabolism KEGG pathways, nucleotide metabolism, xenobiotics biodegradation and metabolism, genetic information processing pathways associated with translation, replication, and repair, and human diseases (Staphylococcus aureus infection) were exclusively enriched in GBS culture-negative communities. CONCLUSIONS: Understanding how perturbations of the vaginal microbiome contribute to pregnancy complications may result in the development of alternative, targeted prevention strategies to prevent maternal GBS colonization. We hypothesized associations between inferred microbial function and GBS status that would need to be confirmed in larger cohorts.
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Microbiota , Complicaciones Infecciosas del Embarazo , Infecciones Estreptocócicas , Recién Nacido , Femenino , Embarazo , Humanos , Mujeres Embarazadas , Tercer Trimestre del Embarazo , Streptococcus agalactiae/genética , ARN Ribosómico 16S/genética , Infecciones Estreptocócicas/microbiología , Vagina/microbiología , Streptococcus/genética , Complicaciones Infecciosas del Embarazo/microbiología , Lactobacillus/genética , Microbiota/genéticaRESUMEN
Surface protein display C (SpdC) protein was described as a novel virulence factor of Staphylococcus aureus that affects biofilm formation and pathogenesis and favors resistance to antimicrobials targeting cell wall. We evaluated the possible correlation between spdC gene expression level and virulence as well as antibiotic resistance phenotypes in S. aureus clinical isolates. The antimicrobial susceptibility of S. aureus clinical isolates (n = 100) was determined by the disk diffusion method. Vancomycin susceptibility was determined by the broth microdilution method. The level of the extracellular proteases and delta-hemolysin was evaluated by measuring the proteolysis and hemolysis zone diameters in skim milk and blood agar plates, respectively. Biofilm formation was assayed using the 96-well microtiter plate method. Most of the isolates (81%) were multidrug-resistant and about half of the isolates (49%) were methicillin-resistant S. aureus. Hemolysin, protease, and biofilm production were detectable in 79%, 71%, and 96% of the isolates. No significant correlation was detectable between the level of spdC gene expression and the activity of tested virulence factors or the antimicrobial resistance phenotype. Therefore, the role of SpdC protein as a virulence regulator in S. aureus needs further evaluation together with the determination of the predominant regulators for each virulence factor.
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Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Antibacterianos/farmacología , Proteínas Bacterianas/metabolismo , Biopelículas , Farmacorresistencia Bacteriana/genética , Expresión Génica , Humanos , Pruebas de Sensibilidad Microbiana , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/genética , Virulencia/genética , Factores de Virulencia/genética , Factores de Virulencia/metabolismoRESUMEN
Helicobacter pylori (H. pylori) has been identified as a group-1 definite carcinogen. As of yet, there is no available vaccine for this microorganism. Our study aimed to identify antigenic peptides in H. pylori using an in silico proteomic approach, and to evaluate their effectiveness as potential vaccine candidates. Four different peptide sequences were prioritized using the reverse vaccinology, namely, CagA1, CagA2, VacA, and SabA. Peptides emulsified with Freunde's adjuvant were used to immunize BALB/C mice. Subcutaneously immunized mice were challenged by oral administration of H. pylori. IgG, IgA, IL4, and IL17 were detected in mice sera. Histopathology of the dissected stomach of vaccinated and control mice were assessed using H&E stain. IgG was significantly higher in mice vaccinated with SabA. IL-4 was significantly increased in CagA1, CagA2, VacA, and SabA vaccinated mice compared to the adjuvant group. Additionally, histopathological examination of gastric tissue showed a protective effect in the vaccinated groups compared to adjuvant and PBS groups. Our findings indicate a promising effect of the tested epitopes, particularly the SabA antigen, to induce an immune response against H. pylori.
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Infecciones por Helicobacter , Helicobacter pylori , Animales , Ratones , Adyuvantes Inmunológicos , Anticuerpos Antibacterianos , Antígenos Bacterianos , Vacunas Bacterianas , Infecciones por Helicobacter/prevención & control , Inmunización , Inmunoglobulina G , Ratones Endogámicos BALB C , Proteómica , Vacunas de SubunidadRESUMEN
Antibiotics are often prescribed in acne treatment; however, Propionibacterium acnes and Staphylococcus epidermidis, the two of the major acne-associated bacteria, developed antibiotic resistance. Essential oils (EOs) present a natural, safe, efficacious and multifunctional alternative treatment. This study aimed to assess the potential anti-acne activity of selected seven EOs commonly used in Mediterranean folk medicine. Antimicrobial activity screening of these oils showed oregano to exhibit the strongest antimicrobial activity with minimum inhibitory concentration (MIC) of 0.34 mg/mL and minimum bactericidal concentration (MBC) of 0.67 mg/mL against P. acnes; and MIC of 0.67 mg/mL and MBC of 1.34 mg/mL against S. epidermidis. The composition of the most effective EOs (oregano and thyme) was determined using gas chromatography-mass spectrometry (GC-MS). Monoterpenoid phenols predominated oregano and thyme EO with thymol percentile 99 and 72, respectively. Thymol showed MIC 0.70 mg/mL against both P. acnes and S. epidermidis whereas MBC was 1.40 and 2.80 mg/mL against P. acnes and S. epidermidis, respectively. Moreover, oregano exhibited the strongest anti-biofilm effect against S. epidermidis with MBIC 1.34 mg/mL and killing dynamic time of 12 and 8 h against P. acnes and S. epidermidis, respectively. Oregano, the most effective EO, was formulated and tested as a nanoemulsion in an acne animal mouse model. The formulation showed superior healing and antimicrobial effects compared to the reference antibiotic. Collectively, our data suggested that oregano oil nanoemulsion is a potential natural and effective alternative for treating acne and overcoming the emerging antibiotic resistance.
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Antibacterianos/química , Antibacterianos/farmacología , Aceites Volátiles/química , Aceites Volátiles/farmacología , Origanum/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Acné Vulgar/tratamiento farmacológico , Acné Vulgar/microbiología , Animales , Biopelículas/efectos de los fármacos , Modelos Animales de Enfermedad , Pruebas Antimicrobianas de Difusión por Disco , Emulsiones/química , Cromatografía de Gases y Espectrometría de Masas , Ratones , Nanopartículas/química , Propionibacterium acnes/efectos de los fármacos , Staphylococcus epidermidis/efectos de los fármacosRESUMEN
A clean way to overcome environmental pollution is biodegradation. In this perspective, at the intersection of biodegradation and metagenomics, the degradome is defined as the totality of genes related to the biodegradation of a certain compound. It includes the genetic elements from both culturable and uncultured microorganisms. The possibility of assessing the biodegradation potential of an environmental samples, using a degradome-based polymerase chain reaction, was explored. 2,4-Dichlorophenol (2,4-DCP) was chosen as a model and the use of tfdB gene as a biodegradation marker was confirmed by bioinformatics study of TfdB protein. Five primer pairs were designed for the detection of different tfdB gene families. A total of 16 environmental samples were collected from Egyptian agricultural soils and wastewaters and tested for the presence of 2,4-DCP. The biodegradation capacity of 2,4-DCP was determined, for all isolated consortia, to reach up to 350 mg/l. Metagenomic DNA was extracted directly from the soil samples while successive 2,4-DCP-degrading microbial communities were enriched, with increasing concentrations of 2,4-DCP, then their DNA was extracted. The extracted DNA was tested for the distribution of the tfdB gene using a degradome-based polymerase chain reaction. tfdB-1 and tfdB-2 were detected in 5 and 9 samples, respectively. However, the co-existence of both genes was detected only in five samples. All tfdB positive samples were capable of 2,4-DCP degradation. The developed approach of assessing the potential of different environments for degrading 2,4-DCP was successfully measured in terms of accuracy (81.25%) and specificity (100%).
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Clorofenoles/metabolismo , Contaminantes Ambientales/metabolismo , Redes y Vías Metabólicas , Oxigenasas de Función Mixta/análisis , Reacción en Cadena de la Polimerasa/métodos , Microbiología del Suelo , Biotransformación , Egipto , Metagenómica/métodos , Oxigenasas de Función Mixta/genéticaRESUMEN
BACKGROUND: The maternal near-miss approach has been increasingly used as a tool to evaluate and improve the quality of care in maternal health. We report findings from the formative stage of a World Health Organization (WHO) funded implementation research study that was undertaken to collect primary data at the facility level on the prevalence, characteristics, and management of maternal near-miss cases in four major public referral hospitals - one each in Egypt, Lebanon, Palestine and Syria. METHODS: We conducted a cross sectional study of maternal near-miss cases in the four contexts beginning in 2011, where we collected data on severe maternal morbidity in the four study hospitals, using the WHO form (Individual Form HRP A65661). In each hospital, a research team including trained hospital healthcare providers carried out the data collection. RESULTS: A total of 9,063 live birth deliveries were reported during the data collection period across the four settings, with a total of 77 cases of severe maternal outcomes (71 maternal near-miss cases and 6 maternal deaths). Higher indices for the maternal mortality index were found in both Al Galaa hospital, in Egypt (8.6%) and Dar Al Tawleed hospital in Syria (14.3%), being large referral hospitals, compared to Ramallah hospital in Palestine and Rafik Hariri University hospital in Lebanon. Compared to the WHO's Multicountry Survey using the same data collection tool, our study's mortality indices are higher than the index of 5.6% among countries with a moderate maternal mortality ratio in the WHO Survey. Overall, haemorrhage-related complications were the most frequent conditions among maternal near-miss cases across the four study hospitals. In all hospitals, coagulation dysfunctions (76.1%) were the most prevalent dysfunction among maternal near-miss cases, followed by cardiovascular dysfunctions. The coverage of key evidence-based interventions among women experiencing a near-miss was either universal or very high in the study hospitals. CONCLUSIONS: Findings from this formative stage confirmed the need for quality improvement interventions. The high reported coverage of the main clinical interventions in the study hospitals would appear to be in contradiction with the above findings as the level of coverage of key evidence-based interventions was high.
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Nacimiento Vivo , Servicios de Salud Materna/estadística & datos numéricos , Mortalidad Materna , Complicaciones del Trabajo de Parto/epidemiología , Adulto , Estudios Transversales , Egipto/epidemiología , Femenino , Hospitales Públicos , Humanos , Líbano/epidemiología , Medio Oriente/epidemiología , Embarazo , Siria/epidemiología , Organización Mundial de la Salud , Adulto JovenRESUMEN
Purpose: The purpose of this study is to investigate how smartphone addiction and self-regulation failure influence students' academic life satisfaction considering the impacts of students' mind wandering and cognitive failures. It also sought to look at how students' minds wander, and cognitive failures are affected by smartphone addiction and self-regulation failure among university students. Methods: The WarpPLS-SEM software was used to analyze the research data retrieved from a sample of 950 undergraduate students from universities in Egypt and the Kingdom of Saudi Arabia (KSA). Results: In both countries, the findings revealed that students' smartphone addiction and self-regulation failures negatively affect students' academic life satisfaction and positively affect students' mind wandering and cognitive failures. Additionally, smartphone addiction is positively related to failures of students' self-regulation. Besides the negative influences of students' cognitive failures on their academic life satisfaction, cognitive failures mediated negatively the relationship between mind wandering and students' academic life satisfaction. Finally, students' mind wandering mediated the relationship between smartphone addiction, self-regulation failure, and academic life satisfaction. Discussion: The study introduces fresh insights into the study variables that can be used to expand the literature on academic life satisfaction. The study provides theoretical and practical contributions to students, educators, and policymakers of education.
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The world has witnessed tremendous advancements in nano-base applications. Zinc oxide nanoparticles (ZON) are widely used in food industry and medicine. Although their application is of important value, they may cause toxicity to body tissues. Peripheral blood mononuclear cells (PBMCs) proved its efficacy in tissue regeneration especially when it is preconditioned by activated platelet supernatant (APS). The aim of this study is to evaluate the effect of ZON on the gastric mucosa and the therapeutic role of the PBMCs preconditioned by APS in rats. Ten rats were donors and fifty rats were recipients. The recipients were divided into; control group, ZON group (10 mg/kg/day orally for five days) and preconditioned PBMCs group (1×107 once intravenously 24 hours after ZON). Gastric specimens were processed for histological, immunohistochemical, biochemical and quantitative real-time polymerase chain reaction studies. ZON group showed marked structural changes in the gastric mucosa. There was desquamation or deep ulceration of the epithelium. Cytoplasmic vacuoles and pyknotic nuclei were in glandular cells. Reduced proliferating cell nuclear antigen and increased tumor necrosis factor-α were in epithelial cells. There were significant elevation in malondialdahyde and reduction in glutathione, superoxide dismutase, and catalase. Enhancement in mRNA expression of nuclear factor kappa-B and cyclooxygenase-2 was detected. The preconditioned PBMCs group showed significant improvement of all parameters. So, ZON had cytotoxic effects on the gastric mucosa and the preconditioned PBMCs had a therapeutic effect on gastric mucosal damage after ZON.
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BACKGROUND: Helicobacter pylori (H. pylori) is significantly linked to various diseases that seriously impact human health, such as gastric ulcers, chronic gastritis and gastric adenocarcinoma. METHODS: The compositional shifts in bacterial communities of the orointestinal axis were surveyed pre/post-eradication of H. pylori. In total, 60 samples, including stool and salivary specimens, were collected from 15 H. pylori-positive individuals (HPP) before beginning and 2 months after receiving the eradication therapy. The V3-V4 regions of the 16S rRNA gene were sequenced using MiSeq. RESULTS: Overall, oral microbiomes were collectively more diverse than the gut microbiomes (Kruskal-Wallis; p = 3.69 × 10-5). Notably, the eradication of H. pylori was associated with a significant reduction in the bacterial diversity along the orointestinal axis (Wilcoxon rank sum test; p = 6.38 × 10-3). Interestingly, the oral microbiome of HPP showed a positive correlation between Proteobacteria and Fusobacteria, in addition to a significant predominance of Streptococcus, in addition to Eubacterium_eligens, Haemophilus, Ruminococcaceae, Actinomyces and Staphylococcus. On the other hand, Fusobacterium, Veillonella, Catenibacterium, Neisseria and Prevotella were significantly enriched upon eradication of H. pylori. Generally, Bacteroidetes and Fusobacteria positively coexisted during H. pylori infection along the orointestinal axis (r = 0.67; p = 0.0006). The eradication of H. pylori was positively linked to two distinctive orotypes (O3 and O4). Orotype O4 was characterized by a robust abundance of Veillonella and Fusobacteria. The gut microbiomes during H. pylori infection showed a remarkable predominance of Clostridium_sensu_stricto_1 and Escherichia_Shigella. Likewise, Bifidobacterium and Faecalibacterium were significantly enriched upon eradication of H. pylori. CONCLUSIONS: Finally, the impact of eradication therapy clearly existed on the representation of certain genera, especially in the oral microbiome, which requires particular concern in order to counteract and limit their subsequent threats.
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Nosocomial infections caused by microbial biofilm formation on biomaterial surfaces such as urinary catheters are complicated by antibiotic resistance, representing a common problem in hospitalized patients. Therefore, we aimed to modify silicone catheters to resist microbial adherence and biofilm formation by the tested microorganisms. This study used a simple direct method to graft poly-acrylic acid onto silicone rubber films using gamma irradiation to endow the silicone surface with hydrophilic carboxylic acid functional groups. This modification allowed the silicone to immobilize ZnO nanoparticles (ZnO NPs) as an anti-biofilm. The modified silicone films were characterized by FT-IR, SEM, and TGA. The anti-adherence ability of the modified silicone films was evidenced by the inhibition of biofilm formation by otherwise strong biofilm-producing Gram-positive, Gram-negative, and yeast clinical isolates. The modified ZnO NPs grafted silicone showed good cytocompatibility with the human epithelial cell line. Moreover, studying the molecular basis of the inhibitory effect of the modified silicone surface on biofilm-associated genes in a selected Pseudomonas aeruginosa isolate showed that anti-adherence activity might be due to the significant downregulation of the expression of lasR, lasI, and lecB genes by 2, 2, and 3.3-fold, respectively. In conclusion, the modified silicone catheters were low-cost, offering broad-spectrum anti-biofilm activity with possible future applications in hospital settings.
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Introduction: New Delhi metallo-ß-lactamase (NDM)-producing K. pneumoniae poses a high risk, especially among Egyptian pediatric patients who consume carbapenems antibiotics very widely and without adequate diagnostic sources. In addition, presence of efflux pump genes such as OqxAB increases resistance against many groups of antimicrobials which exacerbates the problem faced for human health. This study aimed to determine NDM variants among K. pneumoniae strains isolated from pediatric patients in Egypt, analyze the presence of OqxAB genes, and molecular characterization of blaNDM-5-positive K. pneumoniae. Methods: Fifty-six K. pneumoniae isolates were recovered from pediatric patients, and tested for carbapenemase by modified carbapenem inactivation methods (mCIM) test. Minimum inhibitory concentrations of meropenem and colistin were determined by meropenem E-test strips and broth microdilution, respectively. PCR was used for the detection of the resistant genes (ESBL gene (blaCTX-M), carbapenemase genes (blaNDM, blaKPC) colistin resistant (mcr1, mcr2)) and genes for efflux pump (oqxA and oqxB). BlaNDM was sequenced. The effect of efflux pump in NDM-5-producing isolates was assessed by measuring MIC of ciprofloxacin and meropenem before and after exposure to the carbonyl cyanide 3-chlorophenylhydrazone (CCCP). The horizontal gene transfer ability of blaNDM-5 was determined using liquid mating assay and PCR-based replicon typing (PBRT) was done to determine the major plasmid incompatibility group. Results: Twenty-nine isolates were positive for blaNDM-1, nine isolates were positive for blaNDM-5, and 15 isolates were positive for blaKPC. There is a significant increase of meropenem MIC of NDM-5-positive isolates compared with NDM-1-positive isolates. In addition, 38 isolates were positive for CTX-M, and 15 isolates were positive for mcr1. Both OqxA and OqxB were detected in 26 isolates and 13 isolates were positive for OqxA while 11 isolates were positive for OqxB only. All NDM-5-producing isolates except one isolate could transfer their plasmids by conjugation to their corresponding transconjugants (E. coli J53). Plasmid replicon typing showed that FII was predominant in NDM-5-producing K. pneumoniae. Similar strains were found between the three isolates and similarity was also detected between the two isolates. Conclusion: The highly resistant K. pneumoniae producing blaNDM-5 type was firstly isolated from pediatric patients. The association of efflux pump genes such as OqxAB is involved in resistance to ciprofloxacin. This highlighted the severity risk of blaNDM-5-positive K. pneumonia as it could transfer blaNDM-5 to other bacteria and has more resistance against carbapenems. This underlines the importance of continuous monitoring of infection control guidelines, and the urgent need for a national antimicrobial stewardship plan in Egyptian hospitals.
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PURPOSE: Ligamentotaxis is a well-established treatment modality for treating challenging articular fractures. Many devices have been evolved to apply this principle to complex proximal interphalangeal joint (PIPJ) fractures. Although they gave satisfactory results, these devices were sometimes costly, complex and cumbersome. The aim of this study was to evaluate the short-term functional and radiological outcomes of treating complex intra-articular PIPJ fractures using a simplified, preloaded Kirschnerwire (Kwire)-based dynamic external fixator. METHODS: Twenty consecutive patients with intraarticular PIPJ fractures, who fulfilled the study selection criteria, have been treated during 2018 and included in this prospective study after the approval of the responsible institutional ethics committee. Plain radiographs were used for assessing fracture reduction, congruity and healing. The visual analogue sore (VAS) and the Michigan Hand Outcome Questionnaire (MHQ) were used for functional evaluation. PIPJ range of motion (ROM) and hand grip-strength were also assessed. RESULTS: At the final follow-up, all patients had no residual pain. The average PIPJ-ROM was 76.4 ± 23.51°, and the average grip-strength was 85 ± 13.95% as compared to the healthy side. The mean normalized MHQ score was 83 ± 12.63 points, with 4, 13, and 3 patients had excellent, good, and fair results retrospectively. Complications included pin tract infection (one case), stress fracture related to the applied wires (one case), and flexion contractures (four cases; three of them were symptomatic). CONCLUSIONS: The used fixator technique is simple, reliable, available, reproducible, time-saving and cost-effective for managing complex PIPJ fractures while allowing early joint mobilization, which proven effective in achieving high satisfactory functional results.
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Articulaciones de los Dedos , Fuerza de la Mano , Fijadores Externos , Articulaciones de los Dedos/diagnóstico por imagen , Articulaciones de los Dedos/cirugía , Humanos , Estudios Prospectivos , Rango del Movimiento Articular , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Effective eradication therapy for Helicobacter pylori is a worldwide demand. Aspartate α-decarboxylase (ADC) was reported as a drug target in H. pylori, in an in silico study, with malonic acid (MA) as its inhibitor. We evaluated eradicating H. pylori infection through ADC inhibition and the possibility of resistance development. MA binding to ADC was modeled via molecular docking. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of MA were determined against H. pylori ATCC 43504, and a clinical H. pylori isolate. To confirm selective ADC inhibition, we redetermined the MIC in the presence of products of the inhibited enzymatic pathway: ß-alanine and pantothenate. HPLC was used to assay the enzymatic activity of H. pylori 6x-his tagged ADC in the presence of different MA concentrations. H. pylori strains were serially exposed to MA for 14 passages, and the MICs were determined. Cytotoxicity in different cell lines was tested. The efficiency of ADC inhibition in treating H. pylori infections was evaluated using a Sprague-Dawley (SD) rat infection model. MA spectrum of activity was determined in different pathogens. MA binds to H. pylori ADC active site with a good docking score. The MIC of MA against H. pylori ranged from 0.5 to 0.75 mg/mL with MBC of 1.5 mg/mL. Increasing ß-alanine and pantothenate concentrations proportionally increased MA MIC. The 6x-his tagged ADC activity decreased by increasing MA concentration. No resistance to ADC inhibition was recorded after 14 passages; MA lacked cytotoxicity in all tested cell lines. ADC inhibition effectively eradicated H. pylori infection in SD rats. MA had MIC between 0.625 to 1.25 mg/mL against the tested bacterial pathogens. In conclusion, ADC is a promising target for effectively eradicating H. pylori infection that is not affected by resistance development, besides being of broad-spectrum presence in different pathogens. MA provides a lead molecule for the development of an anti-helicobacter ADC inhibitor. This provides hope for saving the lives of those at high risk of infection with the carcinogenic H. pylori.
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Aim: The authors aimed to examine antibiotic resistance genes and representative virulence determinants among 100 Klebsiella pneumoniae isolates with an emphasis on capsular serotypes and clonality of some of the isolates. Methods: PCR amplification of (rmpA, rmpA2, iutA, iroN and IncHI1B plasmid) and (NDM, OXA-48, KPC, CTX-M-15, VIM, IMP, SPM) was conducted. Wzi sequencing and multilocus sequence typing (MLST) were performed. Results: K2 was the only detected serotype in the authors' collection. RMPA2 was the most common capsule-associated virulence gene detected. All studied isolates harbored OXA-48-like (100%) and NDM (43%) (n = 43). ST147 was the most common sequence type. Conclusion: This work provides insight into the evolution of the coexistence of virulence and resistance genes in a tertiary healthcare setting in Cairo, Egypt.
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Infección Hospitalaria , Infecciones por Klebsiella , Antibacterianos/farmacología , Infección Hospitalaria/epidemiología , Humanos , Klebsiella , Infecciones por Klebsiella/epidemiología , Klebsiella pneumoniae , Tipificación de Secuencias Multilocus , Virulencia/genética , beta-Lactamasas/genéticaRESUMEN
Azo dyes impact the environment and deserve attention due to their widespread use in textile and tanning industries and challenging degradation. The high temperature, pH, and salinity used in these industries render industrial effluent decolorization and detoxification a challenging process. An enrichment technique was employed to screen for cost-effective biodegraders of Direct Red 81 (DR81) as a model for diazo dye recalcitrant to degradation. Our results showed that three mixed bacterial cultures achieved ≥80% decolorization within 8 h of 40 mg/L dye in a minimal salt medium with 0.1% yeast extract (MSM-Y) and real wastewater. Moreover, these mixed cultures showed ≥70% decolorization within 24 h when challenged with dye up to 600 mg/L in real wastewater and tolerated temperatures up to 60 °C, pH 10, and 5% salinity in MSM-Y. Azoreductase was the main contributor to DR81 decolorization based on crude oxidative and reductive enzymatic activity of cell-free supernatants and was stable at a wide range of pH and temperatures. Molecular identification of azoreductase genes suggested multiple AzoR genes per mixed culture with a possible novel azoreductase gene. Metabolite analysis using hyphenated techniques suggested two reductive pathways for DR81 biodegradation involving symmetric and asymmetric azo-bond cleavage. The DR81 metabolites were non-toxic to Artemia salina nauplii and Lepidium sativum seeds. This study provided evidence for DR81 degradation using robust stress-tolerant mixed cultures with potential use in azo dye wastewater treatment.
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One strategy to manage resistant pathogens and develop potential anticancer drugs is the search for new, promising, and cost-effective medicinal benefits in the field of bioactive metabolites derived from mushrooms. In the current study, Egyptian cultivated Pleurotus ostreatus fruiting bodies polar extract was prepared to evaluate its antimicrobial activities as well as its cytotoxic effect on various cancer cell lines. The Pleurotus ostreatus polar extract (PoPE) was characterized by its phenolic and flavonoid content. The phenolics and flavonoids of PoPE were 6.94 and 0.15 mg/g, respectively. P. ostreatus polar extract showed potent antimicrobial activity against four pathogens, including Candida albicans, Staphylococcus aureus, Micrococcus luteus, and Escherichia coli. PoPE was found to inhibit Fusarium oxysporum (47%), Fusarium solani (28%) as well as Rhizoctonia solani (21%). PoPE was found to be 13 times more selective and toxic to MCF-7 cells than Vero normal cells, with the lowest IC50 value (4.5 µg/mL), so they were selected to examine the potential cytotoxic effects of PoPE. In MCF-7 cells, PoPE appeared to promote cell cycle arrest in the sub-G1 stage, as well as apoptosis. It significantly increased TNF-α production while decreasing IL-6 levels. PoPE's total antioxidant capacity, lipid peroxide, and glutathione reductase activity were recorded 0.14 ± 0.02 mM/L, 15.60 ± 0.015 nmol/mL, and 9.50 ± 1.30 U/L, respectively. The existence of different bioactive metabolites was investigated via GC-MS, which confirmed the presence of 15 compounds with well-known biological activity.
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BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disabling autoimmune disorder. Little is known regarding the association between the gut microbiome and etiopathogenesis of RA. We aimed to dissect the differences in gut microbiomes associated with RA in comparison to healthy individuals and, in addition, to identify the shifts in the bacterial community in association with disease activity; Methods: In order to identify compositional shifts in gut microbiomes of RA patients, V3-V4 hypervariable regions of 16S rRNA were sequenced using Illumina MiSeq. In total, sixty stool samples were collected from 45 patients with RA besides 15 matched healthy subjects; Results: Notably, RA microbiomes were significantly associated with diverse bacterial communities compared with healthy individuals. Likewise, a direct association between bacterial diversity and disease activity was detected in RA patients (Kruskal Wallis; p = 0.00047). In general, genus-level analysis revealed a positive coexistence between RA and Megasphaera, Adlercreutzia, Ruminococcus, Bacteroides, Collinsella, and Acidaminococcus. Furthermore, Spearman correlation analysis significantly stratified the most dominant genera into distinct clusters that were mainly based on disease activity (r ≥ 0.6; p ≤ 0.05). The predictive metabolic profile of bacterial communities associated with RA could support the potential impact of gut microbiomes in either the development or recovery of RA; Conclusions: The overall shifts in bacterial composition at different disease statuses could confirm the cross-linking of certain genera either to causation or progression of RA.
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There is an urgent need to develop and synthesize new anti-influenza drugs with activity against different strains, resistance to mutations, and suitability for various populations. Herein, we tested in vitro and in vivo the antiviral activity of new 1,2,3-triazole glycosides incorporating benzimidazole, benzooxazole, or benzotriazole cores synthesized by using a click approach. The Cu-catalyzation strategy consisted of 1,3-dipolar cycloaddition of the azidoalkyl derivative of the respective heterocyclic and different glycosyl acetylenes with five or six carbon sugar moieties. The antiviral activity of the synthesized glycosides against wild-type and neuraminidase inhibitor resistant strains of the avian influenza H5N1 and human influenza H1N1 viruses was high in vitro and in mice. Structure-activity relationship studies showed that varying the glycosyl moiety in the synthesized glycosides enhanced antiviral activity. The compound (2R,3R,4S,5R)-2-((1-(Benzo[d]thiazol-2-ylmethyl)-1H-1,2,3-triazol-4-yl)methoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate (Compound 9c) had a 50% inhibitory concentration (IC50) = 2.280 µM and a ligand lipophilic efficiency (LLE) of 6.84. The compound (2R,3R,4S,5R)-2-((1-((1H-Benzo[d]imidazol-2-yl)methyl)-1H-1,2,3-triazol-4-yl)methoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate had IC50 = 2.75 µM and LLE = 7.3 after docking analysis with the H5N1 virus neuraminidase. Compound 9c achieved full protection from H1N1 infection and 80% protection from H5N1 in addition to a high binding energy with neuraminidase and was safe in vitro and in vivo. This compound is suitable for further clinical studies as a new neuraminidase inhibitor.
RESUMEN
Purpose: To investigate the compositional and functional characteristics of T1DM-associated gut microbiota in two Egyptian cities and to study the geographical locality effects. Patients and Methods: This case-control study included 32 children with controlled T1DM and 16 controls, selected from two different regions of Egypt. The gut microbiota of both diabetic and control children was analyzed through 16S rRNA gene sequencing; this was done using the Illumina MiSeq platform. Results: Consistent findings among the diabetic children included significantly lower alpha diversity than the control children, as well as a lower mean Firmicutes/Bacteroidetes (F/B) ratio, and reduced proportions of Firmicutes and the genera Prevotella and Ruminococcus. In the diabetic children, there were also significantly enriched representations of Actinobacteria, Bacteroidetes, and Proteobacteria and the genera Lactobacilli, Bacteroides, and Faecalibacterium. When comparing the two diabetic groups, the Ismailia group (IsDM) was found to have a significantly higher F/B ratio and diversity indices, with resultant differences at the functional level. Conclusion: There are a number of consistent changes in the microbiota profile characterizing the diabetic groups irrespective of the geographical location including significantly lower alpha diversity, mean Firmicutes/ Bacteroidetes (F/B) ratio, and reduced proportions of Firmicutes and genera Prevotella and Ruminococcus. There are also significantly enriched representations of Actinobacteria, Bacteroidetes, and Proteobacteria and genera Lactobacilli, Bacteroides, and Faecalibacterium pointing to the greater driving power of the disease.