Otpornost bakterija Escherichia coli i Pseudomonas aeruginosa na karbapenem u antilope (Antilope cervicapra) i leoparda (Panthera pardus) iz zatočeništva u Indiji

The study aimed to investigate the occurrence of carbapenem resistant E. coli and P. aeruginosa in apparently healthy, captive blackbucks and leopards of India. Faecal samples of blackbucks (n = 7) and leopards (n = 7) were processed to isolate carbapenem resistant E. coli (CRE) and P. aeruginosa (CRP). Forty (leopards n = 26; blackbuck n = 14) E. coli and two P. aeruginosa (blackbuck n = 2) samples were isolated from the faecal samples (n = 14). Eleven carbapenem resistant isolates were recovered, of which 10 were CRE and one was CRP. The minimum inhibitory concentration (MIC) was determined for meropenem for carbapenem resistant isolates and was between 8 and 64 μg/mL. All the CRE and CRP were phenotypically multidrug resistant, and six CRE were extended-spectrum beta- lactamases (ESBL) producers. On genotypic screening, seven CRE and one CRP were positive for the blaNDM carbapenemase gene. Efflux pump-mediated carbapenem resistance was noticed in four CRE isolates (36.4%, 4/11). Of the six ESBL producing CRE, four isolates carried blaCTX-M-1 genes. The CRE isolates also harbored blaTEM-1, blaAmpC, qnrA, qnrB, qnrS, tetA, tetB and sul1 resistance genes. On Shiga toxin virulence screening, Stx1, Stx2 genes were detected in two and one isolates, respectively. Plasmid typing of CRE revealed that the blaNDM genes were carried on an Incl1 plasmid. The plasmid multilocus sequence typing (pMLST) of the isolates showed the Sequence Type (ST) 297. The occurrence of carbapenem resistance bacteria in captive wildlife should be a major public health priority.Cilj rada bio je istražiti slučajeve otpornosti bakterija E. coli i P. aeruginosa na karbapenem u zdravih antilopa i leoparda iz zatočeništva u Indiji. Uzorci izmeta antilopa (n = 7) i leoparda (n = 7) obrađeni su kako bi se izolirale bakterije E. coli (CRE) i P. aeruginosa (CRP) otporne na karbapenem. Iz uzoraka izmeta (n = 14) dobiveno je 40 izolata (leopard n = 26, antilopa n = 14) E. coli i 2 izolata P. aeruginosa (antilopa n = 2). Pronađeno je 11 izolata otpornih na karbapenem, od kojih je 10 E. coli i 1 P. aeruginosa. Određena je minimalna inhibicijska koncentracija (MIK) za meropenem za izolate otporne na karbapenem, od 8 za E. coli i 64 μg/mL za P. aeruginosa. Svi izolati E. coli i P. aeruginosa fenotipski su bili otporni na širok spektar lijekova, a 6 izolata E. coli proizvodilo je beta- laktamaze širokog spektra (ESBL). Genotipskim probirom 7 izolata E. coli i 1 izolat P. aeruginosa bili su pozitivni na karbapenemaza gen blaNDM. Otpornost na karbapenem putem efluks pumpe zabilježena je u 4 izolata E. coli (36,4 %, 4/11). Od 6 ESBL producirajućih CRE, 4 izolata nosila su gen blaCTX-M-1. Izolati E. coli također su sadržavali blaTEM-1, blaAmpC, qnrA, qnrB, qnrS, tetA, tetB i sul1 gene otpornosti. Pretragom na šiga-toksin, Stx1 i Stx2 geni utvrđeni su u dva odnosno jednom izolatu. Tipiziranje plazmida CRE otkrilo je prisutnost blaNDM gena na Incl1 plazmidu. Multilokusno tipiziranje sekvencija plazmida (pMLST) izolata otkrilo je sekvenciju tipa (ST) 297. Pojava otpornosti bakterija na karbapenem u divljih životinja iz zatočeništva trebala bi biti javnozdravstveni prioritet

Molekularna karakterizacija iz psa izdvojenog izolata bakterije Escherichia coli koji proizvodi prošireni spektrum beta-laktamaza i New Delhi metalo-beta-laktamazu-1 (blaNDM1) - prikaz slučaja

In this article, we report the molecular characterization of extensively drug resistant (XDR), extended spectrum, class C beta-lactamases and NDM-1 carbapenemase producing E. coli, isolated from the scrotal fluid of a 3-year-old male dog. In an antibiotic susceptibility test the E. coli isolate was susceptible only to tigecycline and resistant to all clinically applicable antibiotics tested in the study. The minimum inhibitory concentration (MIC) of meropenem, cefotaxime and cefepime was 256, 128 and 64 µg/mL, respectively. On genotypic screening by PCR, the isolate was positive for blaNDM, blaCTX-M, blaAmpC, blaTEM and sul1 genes. The isolate was a ESBL, AmpC and metalo beta-lactamase producer. On molecular pathotyping, the isolate harbored the Shiga toxin producing gene (Stx2). The extensively drug resistant, carbapenem resistant and ESBL producing E. coli constitutes a major public health concern, since there is a great chance of dissemination of resistance genes to humans due to the close association of humans and companion animals. To the best of our knowledge, this is the first report of blaNDM1 isolated from a dog in India.U radu se izvješćuje o molekularnoj karakterizaciji bakterije E. coli izdvojene iz skrotalne tekućine psa, iznimno otporne na antibiotike širokog spektra, koja proizvodi klasu C beta-laktamaza i NDM-1 karbapenemazu. Pas je bio u dobi od od tri godine. Izolat E. coli bio je osjetljiv samo na tigeciklin, a otporan na sve antibiotike primjenjivane u kliničkoj praksi. Minimalna inhibicijska koncentracija (MIC) za meropenem iznosila je 256, cefotaksim 128 i cefepim 64 µg/mL. Pretragom genotipa lančanom reakcijom polimerazom izolat je bio pozitivan na gene blaNDM, blaCTX-M, blaAmpC, blaTEM i sul1. Proizvodio je ESBL, AmpC i metalo-beta-laktamazu. Molekularnom patotipizacijom dokazano je da posjeduje gen za shiga-toksin (Stx2). E. coli otporna na karbapenem, koja proizvodi beta-laktamaze širokog spektra, velika je prijetnja za javno zdravstvo s obzirom na to da postoji velika mogućnost prijenosa E. coli s genom za rezistenciju na ljude u bliskom dodiru s kućnim ljubimcima. Ovo je prvo izvješće o blaNDM1 dokazanom u psa u Indiji

Sirtuin 6 inhibition protects against glucocorticoid-induced skeletal muscle atrophy by regulating IGF/PI3K/AKT signaling

Chronic activation of stress hormones such as glucocorticoids leads to skeletal muscle wasting in mammals. However, the molecular events that mediate glucocorticoid-induced muscle wasting are not well understood. Here, we show that SIRT6, a chromatin-associated deacetylase indirectly regulates glucocorticoid-induced muscle wasting by modulating IGF/PI3K/AKT signaling. Our results show that SIRT6 levels are increased during glucocorticoid-induced reduction of myotube size and during skeletal muscle atrophy in mice. Notably, overexpression of SIRT6 spontaneously decreases the size of primary myotubes in a cell-autonomous manner. On the other hand, SIRT6 depletion increases the diameter of myotubes and protects them against glucocorticoid-induced reduction in myotube size, which is associated with enhanced protein synthesis and repression of atrogenes. In line with this, we find that muscle-specific SIRT6 deficient mice are resistant to glucocorticoid-induced muscle wasting. Mechanistically, we find that SIRT6 deficiency hyperactivates IGF/PI3K/AKT signaling through c-Jun transcription factor-mediated increase in IGF2 expression. The increased activation, in turn, leads to nuclear exclusion and transcriptional repression of the FoxO transcription factor, a key activator of muscle atrophy. Further, we find that pharmacological inhibition of SIRT6 protects against glucocorticoid-induced muscle wasting in mice by regulating IGF/PI3K/AKT signaling implicating the role of SIRT6 in glucocorticoid-induced muscle atrophy.Fil: Mishra, Sneha. No especifíca;Fil: Cosentino, Claudia. Harvard Medical School; Estados UnidosFil: Tamta, Ankit Kumar. No especifíca;Fil: Khan, Danish. No especifíca;Fil: Srinivasan, Shalini. No especifíca;Fil: Ravi, Venkatraman. No especifíca;Fil: Abbotto, Elena. Università degli Studi di Genova; ItaliaFil: Arathi, Bangalore Prabhashankar. No especifíca;Fil: Kumar, Shweta. No especifíca;Fil: Jain, Aditi. No especifíca;Fil: Ramaian, Anand S.. No especifíca;Fil: Kizkekra, Shruti M.. No especifíca;Fil: Rajagopal, Raksha. No especifíca;Fil: Rao, Swathi. No especifíca;Fil: Krishna, Swati. No especifíca;Fil: Asirvatham Jeyaraj, Ninitha. Indian Institute of Technology; IndiaFil: Haggerty, Elizabeth R.. Harvard Medical School; Estados UnidosFil: Silberman, Dafne Magalí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Kurland, Irwin J.. No especifíca;Fil: Veeranna, Ravindra P.. No especifíca;Fil: Jayavelu, Tamilselvan. No especifíca;Fil: Bruzzone, Santina. Università degli Studi di Genova; ItaliaFil: Mostoslavsky, Raul. Harvard Medical School; Estados UnidosFil: Sundaresan, Nagalingam R.. No especifíca

An ab initio and AIM investigation into the hydration of 2-thioxanthine

<p>Abstract</p> <p>Background</p> <p>Hydration is a universal phenomenon in nature. The interactions between biomolecules and water of hydration play a pivotal role in molecular biology. 2-Thioxanthine (2TX), a thio-modified nucleic acid base, is of significant interest as a DNA inhibitor yet its interactions with hydration water have not been investigated either computationally or experimentally. Here in, we reported an <it>ab initio </it>study of the hydration of 2TX, revealing water can form seven hydrated complexes.</p> <p>Results</p> <p>Hydrogen-bond (H-bond) interactions in 1:1 complexes of 2TX with water are studied at the MP2/6-311G(d, p) and B3LYP/6-311G(d, p) levels. Seven 2TX^...H₂O hydrogen bonded complexes have been theoretically identified and reported for the first time. The proton affinities (PAs) of the O, S, and N atoms and deprotonantion enthalpies (DPEs) of different N-H bonds in 2TX are calculated, factors surrounding why the seven complexes have different hydrogen bond energies are discussed. The theoretical infrared and NMR spectra of hydrated 2TX complexes are reported to probe the characteristics of the proposed H-bonds. An improper blue-shifting H-bond with a shortened C-H bond was found in one case. NBO and AIM analysis were carried out to explain the formation of improper blue-shifting H-bonds, and the H-bonding characteristics are discussed.</p> <p>Conclusion</p> <p>2TX can interact with water by five different H-bonding regimes, N-H^...O, O-H^...N, O-H^...O, O-H^...S and C-H^...O, all of which are medium strength hydrogen bonds. The most stable H-bond complex has a closed structure with two hydrogen bonds (N(7)-H^...O and O-H^...O), whereas the least stable one has an open structure with one H-bond. The interaction energies of the studied complexes are correlated to the PA and DPE involved in H-bond formation. After formation of H-bonds, the calculated IR and NMR spectra of the 2TX-water complexes change greatly, which serves to identify the hydration of 2TX.</p

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Not AvailableBackground and Aim: Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli are gradually increasing worldwide and carry a serious public threat. This study aimed to determine the antimicrobial resistance pattern of ESBL-producing E. coli isolated from fecal samples of piglets and pig farm workers. Materials and Methods: Fecal samples from <3-month-old piglets (n=156) and farm workers (n=21) were processed for the isolation of ESBL-producing E. coli in MacConkey agar added with 1 μg/mL of cefotaxime. E. coli (piglets=124; farm workers=21) were tested for ESBL production by combined disk method and ESBL E-strip test. Each of the ESBL-positive isolate was subjected to antibiotic susceptibility testing. The ESBL-producing E. coli were further processed for genotypic confirmation to CTX-M gene. Results: A total of 55 (44.4%, 55/124) and nine (42.9%, 9/21) ESBL-producing E. coli were isolated from piglets and farm workers, respectively. Antibiotic susceptibility testing of the ESBL-positive E. coli isolates from piglets and farm workers showed 100% resistance to ceftazidime, cefotaxime, cefotaxime/clavulanic acid, ceftazidime/clavulanic acid, and cefpodoxime. A proportion of 100% (55/55) and 88.9% (8/9) ESBL-positive E. coli were multidrug resistance (MDR) in piglets and farm workers, respectively. On genotypic screening of the ESBL E. coli isolated from piglets (n=55), 15 were positive for the blaCTX-M gene and of the nine ESBL E. coli from farm workers, none were positive for the blaCTX-M gene. Conclusion: Although there was no significant difference in isolation of ESBL-producing E. coli between piglets and farm workers, the ESBL-positive E. coli from piglets showed relatively higher MDR than farm workers.Not Availabl

PARP1 inhibition protects mice against Japanese encephalitis virus infection

Summary: Japanese encephalitis (JE) is a vector-borne viral disease that causes acute encephalitis in children. Although vaccines have been developed against the JE virus (JEV), no effective antiviral therapy exists. Our study shows that inhibition of poly(ADP-ribose) polymerase 1 (PARP1), an NAD+-dependent (poly-ADP) ribosyl transferase, protects against JEV infection. Interestingly, PARP1 is critical for JEV pathogenesis in Neuro-2a cells and mice. Small molecular inhibitors of PARP1, olaparib, and 3-aminobenzamide (3-AB) significantly reduce clinical signs and viral load in the serum and brains of mice and improve survival. PARP1 inhibition confers protection against JEV infection by inhibiting autophagy. Mechanistically, upon JEV infection, PARP1 PARylates AKT and negatively affects its phosphorylation. In addition, PARP1 transcriptionally upregulates PTEN, the PIP3 phosphatase, negatively regulating AKT. PARP1-mediated AKT inactivation promotes autophagy and JEV pathogenesis by increasing the FoxO activity. Thus, our findings demonstrate PARP1 as a potential mediator of JEV pathogenesis that can be effectively targeted for treating JE

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Not AvailableBluetongue (BT) disease poses a constant risk to the livestock population around the world. A better understanding of the risk factors will enable a more accurate prediction of the place and time of high-risk events. Mapping the disease epizootics over a period in a particular geographic area will identify the spatial distribution of disease occurrence. A Geographical Information System (GIS) based methodology to analyze the relationship between bluetongue epizootics and spatial–temporal patterns was used for the years 2000 to 2015 in sheep of Andhra Pradesh, India. Autocorrelation (ACF), partial autocorrelation (PACF), and cross-correlation (CCF) analyses were carried out to find the self-dependency between BT epizootics and their dependencies on environmental factors and livestock population. The association with climatic or remote sensing variables at different months lag, including wind speed, temperature, rainfall, relative humidity, normalized difference vegetation index (NDVI), normalized difference water index (NDWI), land surface temperature (LST), was also examined. The ACF & PACF of BT epizootics with its lag showed a significant positive autocorrelation with a month’s lag (r = 0.41). Cross-correlations between the environmental variables and BT epizootics indicated the significant positive correlations at 0, 1, and 2 month’s lag of rainfall, relative humidity, normalized difference water index (NDWI), and normalized difference vegetation index (NDVI). Spatial autocorrelation analysis estimated the univariate global Moran’s I value of 0.21. Meanwhile, the local Moran’s I value for the year 2000 (r = 0.32) showed a high degree of spatial autocorrelation. The spatial autocorrelation analysis revealed that the BT epizootics in sheep are having considerable spatial association among the outbreaks in nearby districts, and have to be taken care of while making any forecasting or disease prediction with other risk factors.Not Availabl