In vitro activity of BAY 12-8039, a novel 8-methoxyquinolone, compared to activities of six fluoroquinolones against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis

The in vitro activity of a novel 8-methoxyquinolone, BAY 12-8039, against recent clinical isolates of Streptococcus pneumoniae (n = 404), Haemophilus influenzae (n = 330), and Moraxella catarrhalis (n = 250) was evaluated. Activity was compared to those of six other fluoroquinolones: ciprofloxacin, clinafloxacin, levofloxacin, ofloxacin, sparfloxacin and trovafloxacin. BAY 12-8039 and clinafloxacin had the highest levels of activity against S. pneumoniae, both with a MIC at which 90% of the isolates were inhibited (MIC90) of 0.06 microg/ml. Trovafloxacin and sparfloxacin were the next most active agents versus S. pneumoniae (MIC90s = 0.12 microg/ml). No differences in activity against penicillin-susceptible, -intermediate, or -resistant strains of S. pneumoniae were noted for any of the fluoroquinolones tested. MIC90s for the seven fluoroquinolones ranged from 0.008 to 0.06 microg/ml versus H. influenzae and from 0.008 to 0.12 microg/ml for M. catarrhalis. The MICs for two strains of S. pneumoniae and one strain of H. influenzae were noted to be higher than those for the general population of organisms for all of the fluoroquinolones tested. Finally, the activity of BAY 12-8039 versus S. pneumoniae was found to be diminished when MIC determinations were performed with incubation of agar dilution plates or broth microdilution trays in 5 to 7% CO2 versus ambient air

Antimicrobial-drug use and changes in resistance in Streptococcus pneumoniae.

Resistance of Streptococcus pneumoniae to antimicrobial drugs is increasing. To investigate the relationship between antimicrobial use and susceptibility of S. pneumoniae isolates at 24 U.S. medical centers, we obtained data on outpatient antimicrobial-drug use for the regions surrounding 23 of these centers. We found an association between decreased penicillin susceptibility and use of beta-lactam antimicrobial drugs

Controlled lasing from active optomechanical resonators

Planar microcavities with distributed Bragg reflectors (DBRs) host, besides confined optical modes, also mechanical resonances due to stop bands in the phonon dispersion relation of the DBRs. These resonances have frequencies in the sub-terahertz (10E10-10E11 Hz) range with quality factors exceeding 1000. The interaction of photons and phonons in such optomechanical systems can be drastically enhanced, opening a new route toward manipulation of light. Here we implemented active semiconducting layers into the microcavity to obtain a vertical-cavity surface-emitting laser (VCSEL). Thereby three resonant excitations -photons, phonons, and electrons- can interact strongly with each other providing control of the VCSEL laser emission: a picosecond strain pulse injected into the VCSEL excites long-living mechanical resonances therein. As a result, modulation of the lasing intensity at frequencies up to 40 GHz is observed. From these findings prospective applications such as THz laser control and stimulated phonon emission may emerge

Vaccine Escape Recombinants Emerge after Pneumococcal Vaccination in the United States

The heptavalent pneumococcal conjugate vaccine (PCV7) was introduced in the United States (US) in 2000 and has significantly reduced invasive pneumococcal disease; however, the incidence of nonvaccine serotype invasive disease, particularly due to serotype 19A, has increased. The serotype 19A increase can be explained in part by expansion of a genotype that has been circulating in the US prior to vaccine implementation (and other countries since at least 1990), but also by the emergence of a novel “vaccine escape recombinant” pneumococcal strain. This strain has a genotype that previously was only associated with vaccine serotype 4, but now expresses a nonvaccine serotype 19A capsule. Based on prior evidence for capsular switching by recombination at the capsular locus, the genetic event that resulted in this novel serotype/genotype combination might be identifiable from the DNA sequence of individual pneumococcal strains. Therefore, the aim of this study was to characterise the putative recombinational event(s) at the capsular locus that resulted in the change from a vaccine to a nonvaccine capsular type. Sequencing the capsular locus flanking regions of 51 vaccine escape (progeny), recipient, and putative donor pneumococci revealed a 39 kb recombinational fragment, which included the capsular locus, flanking regions, and two adjacent penicillin-binding proteins, and thus resulted in a capsular switch and penicillin nonsusceptibility in a single genetic event. Since 2003, 37 such vaccine escape strains have been detected, some of which had evolved further. Furthermore, two new types of serotype 19A vaccine escape strains emerged in 2005. To our knowledge, this is the first time a single recombinational event has been documented in vivo that resulted in both a change of serotype and penicillin nonsusceptibility. Vaccine escape by genetic recombination at the capsular locus has the potential to reduce PCV7 effectiveness in the longer term

Standardized next-generation sequencing of immunoglobulin and T-cell receptor gene recombinations for MRD marker identification in acute lymphoblastic leukaemia; a EuroClonality-NGS validation study

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Quality control and quantification in IG/TR next-generation sequencing marker identification: protocols and bioinformatic functionalities by EuroClonality-NGS

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In Vitro Intracellular Trafficking of Virulence Antigen during Infection by Yersinia pestis

Yersinia pestis, the causative agent of plague, encodes several essential virulence factors on a 70 kb plasmid, including the Yersinia outer proteins (Yops) and a multifunctional virulence antigen (V). V is uniquely able to inhibit the host immune response; aid in the expression, secretion, and injection of the cytotoxic Yops via a type III secretion system (T3SS)-dependent mechanism; be secreted extracellularly; and enter the host cell by a T3SS-independent mechanism, where its activity is unknown. To elucidate the intracellular trafficking and target(s) of V, time-course experiments were performed with macrophages (MΦs) infected with Y. pestis or Y. pseudotuberculosis at intervals from 5 min to 6 h. The trafficking pattern was discerned from results of parallel microscopy, immunoblotting, and flow cytometry experiments. The MΦs were incubated with fluorescent or gold conjugated primary or secondary anti-V (antibodies [Abs]) in conjunction with organelle-associated Abs or dyes. The samples were observed for co-localization by immuno-fluorescence and electron microscopy. For fractionation studies, uninfected and infected MΦs were lysed and subjected to density gradient centrifugation coupled with immunoblotting with Abs to V or to organelles. Samples were also analyzed by flow cytometry after lysis and dual-staining with anti-V and anti-organelle Abs. Our findings indicate a co-localization of V with (1) endosomal proteins between 10–45 min of infection, (2) lysosomal protein(s) between 1–2 h of infection, (3) mitochondrial proteins between 2.5–3 h infection, and (4) Golgi protein(s) between 4–6 h of infection. Further studies are being performed to determine the specific intracellular interactions and role in pathogenesis of intracellularly localized V

Ezekiel and the Covenant of Friendship

The slippery idea of "spirituality" might, with care, be put to use by biblical exegetes. Spirituality is defined in this paper as the social enactment of religious ideas. Four categories are offered to analyze the biblical witness as a record of spirituality. These categories are, first, an ultimate end; second, an ideal self-image by which this end might be achieved; third, an encoding of teachings in Scripture by which the self-image can be realized or understood; and fourth, a proposal for a way of life that makes achievement of the ultimate end a practical possibility. Accordingly, Ezekiel's "spirituality" may be understood to have, on one hand, an ultimate end of a return of the people to the land with the presence of God; and on the other, an ideal self-image of conversion of the community toward this ultimate end. Then it encodes, in oracles of judgment and deliverance, teachings that enable adherents to form the ideal self-image, and finally, as a way of life that puts these teachings into practice, it proposes a "covenant of friendship" (Ezek 34:25 and 37:36) among the exiled people and between them and their captors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66911/2/10.1177_014610799202200402.pd

Antimicrobial resistance with Streptococcus pneumoniae in the United States, 1997 98.

From November 1997 to April 1998, 1,601 clinical isolates of Streptococcus pneumoniae were obtained from 34 U.S. medical centers. The overall rate of strains showing resistance to penicillin was 29. 5%, with 17.4% having intermediate resistance. Multidrug resistance, defined as lack of susceptibility to penicillin and at least two other non-ss-lactam classes of antimicrobial drugs, was observed in 16.0% of isolates. Resistance to all 10 ss-lactam drugs examined in this study was directly related to the level of penicillin resistance. Penicillin resistance rates were highest in isolates from middle ear fluid and sinus aspirates of children ambulatory-care settings. Twenty-four of the 34 medical centers in this study had participated in a similar study 3 years before. In 19 of these 24 centers, penicillin resistance rates increased 2.9% to 39.2%. Similar increases were observed with rates of resistance to other antimicrobial drugs

Population genetic structure of Streptococcus pneumoniae in Kilifi, Kenya, prior to the introduction of pneumococcal conjugate vaccine.

BACKGROUND: The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced in Kenya in 2011. Introduction of any PCV will perturb the existing pneumococcal population structure, thus the aim was to genotype pneumococci collected in Kilifi before PCV10. METHODS AND FINDINGS: Using multilocus sequence typing (MLST), we genotyped >1100 invasive and carriage pneumococci from children, the largest collection genotyped from a single resource-poor country and reported to date. Serotype 1 was the most common serotype causing invasive disease and was rarely detected in carriage; all serotype 1 isolates were members of clonal complex (CC) 217. There were temporal fluctuations in the major circulating sequence types (STs); and although 1-3 major serotype 1, 14 or 23F STs co-circulated annually, the two major serotype 5 STs mainly circulated independently. Major STs/CCs also included isolates of serotypes 3, 12F, 18C and 19A and each shared ≤ 2 MLST alleles with STs that circulate widely elsewhere. Major CCs associated with non-PCV10 serotypes were predominantly represented by carriage isolates, although serotype 19A and 12F CCs were largely invasive and a serotype 10A CC was equally represented by invasive and carriage isolates. CONCLUSIONS: Understanding the pre-PCV10 population genetic structure in Kilifi will allow for the detection of changes in prevalence of the circulating genotypes and evidence for capsular switching post-vaccine implementation