Primer relevamiento de marcadores de resistencia a antibióticos en Enterobacteriaceae en Cochabamba, Bolivia

Se llevó a cabo un relevamiento molecular de la resistencia a antibióticos de importancia clínica en aislamientos recuperados en Cochabamba, Bolivia. Se estudiaron los genes codificantes de β-lactamasas de espectro extendido y de resistencia a quinolonas de localización plasmídica (PMQR) en un total de 101 aislamientos de enterobacterias resistentes a oximinocefalosporinas recuperados en distintos centros de salud, durante 4 meses (2012-2013). En todos ellos se detectó la presencia de cefotaximasas, las CTX-M grupo 1 fueron las más prevalentes (88,1%). La presencia de blaOXA-1 se detectó en el 76,4% de estos aislamientos. Se observó una elevada proporción de aislamientos resistentes a quinolonas. El gen aac(6′)-Ib-cr fue el determinante PMQR más frecuentemente identificado (83%). Además, 6 aislamientos resultaron ser portadores de qnrB. Por otro lado, cabe remarcar que 7 Escherichia coli presentaron qepA1 (6) y oqxAB (1); se documenta así por primera vez la presencia de oqxAB en Bolivia. Este estudio constituye el primer relevamiento de marcadores de resistencia en aislamientos clínicos de enterobacterias en Cochabamba, Bolivia; de este modo se contribuye al conocimiento regional de la situación epidemiológica, la cual presenta un escenario similar al observado en el resto de Latinoamérica.A molecular survey was conducted in Cochabamba, Bolivia, to characterize the mechanism involved in the resistance to clinically relevant antibiotics. Extended Spectrum β-lactamase encoding genes and plasmid-mediated quinolone resistance (PMQR) markers were investigated in a total of 101 oxyimino-cephalosporin-resistant enterobacteria recovered from different health centers during four months (2012?2013). CTX-M enzymes were detected in all isolates, being the CTX-M-1 group the most prevalent (88.1%). The presence of blaOXA-1 was detected in 76.4% of these isolates. A high quinolone resistance rate was observed among the included isolates. The aac(6′)-Ib-cr gene was the most frequent PMQR identified (83.0%). Furthermore, 6 isolates harbored the qnrB gene. Interestingly, qepA1 (6) and oqxAB (1), were detected in 7 Escherichia coli, being the latter the first to be reported in Bolivia. This study constitutes the first molecular survey on resistance markers in clinical enterobacterial isolates in Cochabamba, Bolivia, contributing to the regional knowledge of the epidemiological situation. The molecular epidemiology observed herein resembles the scene reported in South America.Fil: Saba Villarroel, Paola M.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Gutkind, Gabriel Osvaldo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Di Conza, José Alejandro. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Radice, Marcela Alejandra. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Imprint of the stochastic nature of photon emission by electrons on the proton energy spectra in the laser-plasma interaction

The impact of stochasticity effects (SEs) in photon emissions on the proton energy spectra during laser-plasma interaction is theoretically investigated in the quantum radiation-dominated regime, which may facilitate SEs experimental observation. We calculate the photon emissions quantum mechanically and the plasma dynamics semiclassically via two-dimensional particle-in-cell simulations. An ultrarelativistic plasma generated and driven by an ultraintense laser pulse head-on collides with another strong laser pulse, which decelerates the electrons due to radiation-reaction effect and results in a significant compression of the proton energy spectra because of the charge separation force. In the considered regime the SEs are demonstrated in the shift of the mean energy of the protons up to hundreds of MeV. This effect is robust with respect to the laser and target parameters and measurable in soon available strong laser facilities

Molecular characterization of fluoroquinolone-resistant Mycobacterium tuberculosis clinical isolates from Shanghai, China

China is one of the countries with the highest prevalence of fluoroquinolone-resistant (FQ r) Mycobacterium tuberculosis. Nevertheless, knowledge on the molecular characterization of the FQ r M. tuberculosis strains of this region remains very limited. This study was performed to investigate the frequencies and types of mutations present in FQ r M. tuberculosis clinical isolates collected in Shanghai, China. A total of 206 FQ r M. tuberculosis strains and 21 ofloxacin-sensitive (FQ s) M. tuberculosis strains were isolated from patients with pulmonary tuberculosis in Shanghai. The phenotypic drug susceptibilities were determined by the proportion method, and the mutations inside quinolone resistance-determining region (QRDR) of gyrA and gyrB genes were identified by DNA sequence analyses. Among 206 FQ r M. tuberculosis strains, 44% (90/206) were multidrug-resistant isolates and 39% (81/206) were extensively drug-resistant isolates. Only 9% (19/206) were monoresistant to ofloxacin. In total, 79.1% (163/206) of FQ r isolates harboured mutations in either gyrA or gyrB QRDR. Mutations in gyrA QRDR were found in 75.7% (156/206) of FQ r clinical isolates. Among those gyrA mutants, a majority (75.6%) harboured mutations at amino acid position 94, with D94G being the most frequent amino acid substitution. Mutations in gyrA QRDR showed 100% positive predictive value for FQ r M. tuberculosis in China. Mutations in gyrB were observed in 15.5% (32/206) of FQ r clinical isolates. Ten novel mutations were identified in gyrB. However, most of them also harboured mutations in gyrA, limiting their contribution to FQ r resistance in M. tuberculosis. Our findings indicated that, similar to other geographic regions, mutations in gyrA were shown to be the major mechanism of FQ r resistance in M. tuberculosis isolates. The mutations in gyrA QRDR can be a good molecular surrogate marker for detecting FQ r M. tuberculosis in China. © 2012 Elsevier Inc.postprin

Electron-Angular-Distribution Reshaping in Quantum Radiation-Dominated Regime

Dynamics of an electron beam head-on colliding with an ultraintense focused ultrashort circularly-polarized laser pulse are investigated in the quantum radiation-dominated regime. Generally, the ponderomotive force of the laser fields may deflect the electrons transversely, to form a ring structure on the cross-section of the electron beam. However, we find that when the Lorentz factor of the electron $\gamma$ is approximately one order of magnitude larger than the invariant laser field parameter $\xi$, the stochastic nature of the photon emission leads to electron aggregation abnormally inwards to the propagation axis of the laser pulse. Consequently, the electron angular distribution after the interaction exhibits a peak structure in the beam propagation direction, which is apparently distinguished from the "ring"-structure of the distribution in the classical regime, and therefore, can be recognized as a proof of the fundamental quantum stochastic nature of radiation. The stochasticity signature is robust with respect to the laser and electron parameters and observable with current experimental techniques

Probability and uncertainty in Keynes's The General Theory

Book description: John Maynard Keynes is undoubtedly the most influential Western economist of the twentieth century. His emphasis on the nature and role of uncertainty in economic thought is a dominant theme in his writings. This book brings together a wide array of experts on Keynes' thought such as Gay Tulip Meeks, Sheila Dow and John Davis who discuss, analyse and criticise such themes as Keynesian probability and uncertainty, the foundations of Keynes' economics and the relationship between Keynes' earlier and later thought. The Philosophy of Keynes' Economics is a readable and comprehensive book that will interest students and academics interested in the man and his thought

Detection of mutations in gyrB using denaturing high performance liquid chromatography (DHPLC) among Salmonella enterica serovar Typhi and Paratyphi A

Background:- Fluoroquinolone resistance is mediated by mutations in the quinolone-resistance determining region (QRDR) of the topoisomerase genes. Denaturing high performance liquid chromatography (DHPLC) was evaluated for detection of clinically important mutations in gyrB among Salmonella. Method:- S. Typhi and S. ParatyphiA characterised for mutation in QRDR of gyrA, parC and parE were studied for mutation in gyrB by DHPLC and validated by sequencing. Result:- The DHPLC analysis was able to resolve the test mutant from isolates with wild type gyrB and distinguished mutants from other mutant by peak profile and shift in retention time. Three sequence variants were detected at codon 464, and a novel mutation Ser→Thr was also detected. gyrB mutation was associated with non classical quinolone resistance (NALS-CIPDS) in 34 isolates of S. Typhi only and was distinct from classical quinolone resistance associated with gyrA mutations (NALR-CIPDS). Conclusion: DHPLC is effective for the detection of mutation and can reduce the need forsequencing to detect clinically significant gyrB mutations.

A Crystal Structure of the Bifunctional Antibiotic Simocyclinone D8, Bound to DNA Gyrase

Simocyclinones are bifunctional antibiotics that inhibit bacterial DNA gyrase by preventing DNA binding to the enzyme. We report the crystal structure of the complex formed between the N-terminal domain of the Escherichia coli gyrase A subunit and simocyclinone D8, revealing two binding pockets that separately accommodate the aminocoumarin and polyketide moieties of the antibiotic. These are close to, but distinct from, the quinolone-binding site, consistent with our observations that several mutations in this region confer resistance to both agents. Biochemical studies show that the individual moieties of simocyclinone D8 are comparatively weak inhibitors of gyrase relative to the parent compound, but their combination generates a more potent inhibitor. Our results should facilitate the design of drug molecules that target these unexploited binding pockets

Prediction of Phenotypic Antimicrobial Resistance Profiles From Whole Genome Sequences of Non-typhoidal Salmonella enterica

Surveillance of antimicrobial resistance (AMR) in non-typhoidal Salmonella enterica (NTS), is essential for monitoring transmission of resistance from the food chain to humans, and for establishing effective treatment protocols. We evaluated the prediction of phenotypic resistance in NTS from genotypic profiles derived from whole genome sequencing (WGS). Genes and chromosomal mutations responsible for phenotypic resistance were sought in WGS data from 3,491 NTS isolates received by Public Health England’s Gastrointestinal Bacteria Reference Unit between April 2014 and March 2015. Inferred genotypic AMR profiles were compared with phenotypic susceptibilities determined for fifteen antimicrobials using EUCAST guidelines. Discrepancies between phenotypic and genotypic profiles for one or more antimicrobials were detected for 76 isolates (2.18%) although only 88/52,365 (0.17%) isolate/antimicrobial combinations were discordant. Of the discrepant results, the largest number were associated with streptomycin (67.05%, n = 59). Pan-susceptibility was observed in 2,190 isolates (62.73%). Overall, resistance to tetracyclines was most common (26.27% of isolates, n = 917) followed by sulphonamides (23.72%, n = 828) and ampicillin (21.43%, n = 748). Multidrug resistance (MDR), i.e., resistance to three or more antimicrobial classes, was detected in 848 isolates (24.29%) with resistance to ampicillin, streptomycin, sulphonamides and tetracyclines being the most common MDR profile (n = 231; 27.24%). For isolates with this profile, all but one were S. Typhimurium and 94.81% (n = 219) had the resistance determinants blaTEM-1, strA-strB, sul2 and tet(A). Extended-spectrum β-lactamase genes were identified in 41 isolates (1.17%) and multiple mutations in chromosomal genes associated with ciprofloxacin resistance in 82 isolates (2.35%). This study showed that WGS is suitable as a rapid means of determining AMR patterns of NTS for public health surveillance

Prevalence of mechanisms decreasing quinolone-susceptibility among Salmonella spp. clinical isolates

Fluoroquinolone treatment failure has been reported in patients with nalidixic acid-resistant Salmonella infections. Both chromosomal- and plasmid-mediated quinolone-resistance mechanisms have been described. The objective of this study was to identify the prevalence of these mechanisms in a collection of 41 Salmonella spp. clinical isolates causing acute gastroenteritis, obtained in the Hospital Clinic, Barcelona. The minimum inhibitory concentrations (MICs) of nalidixic acid and ciprofloxacin were determined by Etest. Mutations in the quinolone-resistance determining regions (QRDRs) of the gyrA, gyrB, and parC genes and the presence of the qnr, aac(6′)-Ib-cr, and qepA genes were detected by PCR and DNA sequencing. All isolates showed constitutive expression of an efflux pump. None of the isolates were ciprofloxacin-resistant, whereas 41.5% showed nalidixic acid resistance associated with a mutation in gyrA and overexpression of an efflux pump. Although qnrS1, qnrB6, and qepA were found in four isolates, the expression of these genes was not associated with decreased quinolone susceptibility. Mutations in the gyrA gene and overexpression of an efflux pump were critical for nalidixic acid resistance and decreased susceptibility to ciprofloxacin in these isolates. However, plasmid-mediated quinolone resistance did not seem to play a major role. To our knowledge, this is the first description of qepA in Salmonella. [Int Microbiol 2010; 13(1):15-20