To characterize the genetic determinants of resistance to antituberculosis drugs, we performed a genome-wide association study (GWAS) of 6,465 Mycobacterium tuberculosis clinical isolates from more than 30 countries. A GWAS approach within a mixed-regression framework was followed by a phylogenetics-based test for independent mutations. In addition to mutations in established and recently described resistance-associated genes, novel mutations were discovered for resistance to cycloserine, ethionamide and para-aminosalicylic acid. The capacity to detect mutations associated with resistance to ethionamide, pyrazinamide, capreomycin, cycloserine and para-aminosalicylic acid was enhanced by inclusion of insertions and deletions. Odds ratios for mutations within candidate genes were found to reflect levels of resistance. New epistatic relationships between candidate drug-resistance-associated genes were identified. Findings also suggest the involvement of efflux pumps (drrA and Rv2688c) in the emergence of resistance. This study will inform the design of new diagnostic tests and expedite the investigation of resistance and compensatory epistatic mechanisms.
A simple, eco-friendly, and biomimetic approach using Thymus vulgaris ( T . vulgaris ) leaf extract was developed for the formation of ZnO-Ag nanocomposites (NCs) without employing any stabilizer and a chemical surfactant. T . vulgaris leaf extract was used for the first time, in a novel approach, for green fabrication of ZnO-Ag NCs as a size based reducing agent via the hydrothermal method in a single step. Presence of phenols in T . vulgaris leaf extract has served as both reducing and capping agents that play a critical role in the production of ZnO-Ag NCs. The effect of silver nitrate concentration in the formation of ZnO-Ag NCs was studied. The in-vitro Antimicrobial activity of NCs displayed high antimicrobial potency on selective gram negative and positive foodborne pathogens. Antioxidant activity of ZnO-Ag NCs was evaluated via (2,2-diphenyl-1-picrylhydrazyl) DPPH method. Photocatalytic performance of ZnO-Ag NCs was appraised by degradation of phenol under natural sunlight, which exhibited efficient photocatalytic activity on phenol. Cytotoxicity of the NCs was evaluated using the haemolysis assay. Results of this study reveal that T . vulgaris leaf extract, containing phytochemicals, possess reducing property for ZnO-Ag NCs fabrication and the obtained ZnO-Ag NCs could be employed effectively for biological applications in food science. Therefore, the present study offers a promising way to achieve high-efficiency photocatalysis based on the hybrid structure of semiconductor/metal.
Background Blastocystis, a genetically diverse intestinal parasite with controversial pathogenic potential, has increasingly been incriminated for diarrheal illness in immunocompromised individuals including colorectal cancer (CRC) patients. The aim of the current study was to assess the possible association between Blastocystis infection and CRC condition in Makkah, Saudi Arabia (KSA).MethodsStool samples were collected from 80 non-cancer (NC) and 138 cancer subjects including 74 CRC patients and 64 patients with other cancers outside gastrointestinal tract (COGT). Molecularly confirmed Blastocystis isolates were genetically grouped and subtyped using multiplex polymerase chain reaction with restriction fragment length polymorphism (PCR-RFLP) and sequence-tagged site primers-based PCR (PCR-STS), respectively.Results Blastocystis hominis were confirmed in 29.7, 25 and 15% among CRC, COGT and NC patients, respectively. Obtained Blastocystis isolates were initially categorized into 2 groups (A and C), which were subsequently subtyped into 3 different subtypes; subtype-I (38%), subtype-II (44%) and subtype-V (22%). Interestingly, subtype-I was the most predominantly detected subtype (54.5%) among CRC patients with a significant association risk (COR 7.548; 95% CI: 1.629–34.987; P = 0.004).ConclusionTo the best of our knowledge, the current study is the first to provide genetic insights on the prevalence of Blastocystis hominis among CRC patients in Makkah, KSA. Moreover, the study suggests for a possible association between subtype-I of Blastocystis hominis and CRC, which could indicate a potential influence of Blastocystis on CRC condition. Further studies are required to confirm this association risk and to investigate the possible underlying mechanism of postulated carcinogenic influence of Blastocystis hominis subtype-I.Electronic supplementary materialThe online version of this article (doi:10.1186/s13027-017-0131-z) contains supplementary material, which is available to authorized users.
Plants have been used since ancient times to cure certain infectious diseases, and some of them are now standard treatments for several diseases. Due to the side effects and resistance of pathogenic microorganisms to antibiotics and most drugs on the market, a great deal of attention has been paid to extracts and biologically active compounds isolated from plant species used in herbal medicine. Artemisia absinthium is an important perennial shrubby plant that has been widely used for the treatment of several ailments. Traditionally, A. absinthium has always been of pharmaceutical and botanical importance and used to manage several disorders including hepatocyte enlargement, hepatitis, gastritis, jaundice, wound healing, splenomegaly, dyspepsia, indigestion, flatulence, gastric pain, anemia, and anorexia. It has also been documented to possess antioxidant, antifungal, antimicrobial, anthelmintic, anti-ulcer, anticarcinogenic, hepatoprotective, neuroprotective, antidepressant, analgesic, immunomodulatory, and cytotoxic activity. Long-term use of A. absinthium essential oil may cause toxic and mental disorders in humans with clinical manifestations including convulsions, sleeplessness, and hallucinations. Combination chemotherapies of artemisia extract or its isolated active constituents with the currently available antibabesial or anti-malarial drugs are now documented to relieve malaria and piroplasmosis infections. The current review examines the phytoconstituents, toxic and biological activities of A. absinthium.
BackgroundDespite increasing interest in possible differences in virulence and transmissibility between different genotypes of M. tuberculosis, very little is known about how genotypes within a population change over decades, or about relationships to HIV infection.Methods and Principal FindingsIn a population-based study in rural Malawi we have examined smears and cultures from tuberculosis patients over a 20-year period using spoligotyping. Isolates were grouped into spoligotype families and lineages following previously published criteria. Time trends, HIV status, drug resistance and outcome were examined by spoligotype family and lineage. In addition, transmissibility was examined among pairs of cases with known epidemiological contact by assessing the proportion of transmissions confirmed for each lineage, on the basis of IS6110 RFLP similarity of the M tuberculosis strains. 760 spoligotypes were obtained from smears from 518 patients from 1986–2002, and 377 spoligotypes from cultures from 347 patients from 2005–2008. There was good consistency in patients with multiple specimens. Among 781 patients with first episode tuberculosis, the majority (76%) had Lineage 4 (“European/American”) strains; 9% had Lineage 3 (“East-African/Indian”); 8% Lineage 1 (“Indo-Oceanic”); and 2% Lineage 2 (“East-Asian”); others unclassifiable. Over time the proportion of Lineage 4 decreased from >90% to 60%, with an increase in the other 3 lineages (p<0.001). Lineage 1 strains were more common in those with HIV infection, even after adjusting for age, sex and year. There were no associations with drug resistance or outcome, and no differences by lineage in the proportion of pairs in which transmission was confirmed.ConclusionsThis is the first study to describe long term trends in the four M. tuberculosis lineages in a population. Lineage 4 has probably been longstanding in this population, with relatively recent introductions and spread of Lineages1–3, perhaps influenced by the HIV epidemic.
In the present study, antibiotic residues were detected in milk samples collected from the dairy herds located in Karnataka, India, by microbiological assay. Subsequently, the detected antibiotics were identified as azithromycin and tetracycline, by high-performance liquid chromatography, further both the antibiotics detected in the cow milk samples were found to be at high concentration (9708.7 and 5460 μg kg-1, respectively). We then investigated the effects of temperature and pH on the stabilities of azithromycin and tetracycline to determine the degradation rate constant k using first-order kinetic equation. Results indicated that significant reduction in stability and antibacterial activity of azithromycin solution when subjected to 70 and 100°C for 24 h. While stability of tetracycline was significantly reduced when subjected to 70 and 100°C for 24 h. However no significant reduction in antibacterial activity of tetracycline was observed at respective temperatures when compared with that of control. In addition, the stabilities of azithromycin and tetracycline were found to be decreased in acidic pH 4–5. The results of the present study revealed the high risk of contamination of milk sample with veterinary antibiotics and also demonstrated the effect of temperature and pH on stability of antibiotics. Therefore the study suggest that the qualitative and quantitative screening of milk for the presence of antibiotics need to be strictly performed to ensure safe drinking milk for consumers.
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