Notes

Any vanA vancomycin-resistant Enterococcus faecium ST80 herpes outbreak resulting from one particular importation occasion.
We showed that the tetravalent construct, F1×F1-hFc, containing two sdAb-in-tandem on an Fc scaffold, exhibits more potent neutralization activity against EVA71 than the bivalent sdAb, F1-hFc, for at least 5.8-fold. We also demonstrated that, using a human scavenger receptor class B member 2 (hSCARB2) transgenic mouse model, a half-dose of the F1×F1-hFc provided better protection against EVA71 infection than did the F1-hFc. Thus, our study furnishes important insights into multivalent sdAb engineering against viral infection and provides a novel strategic deployment approach for preparedness of emerging infectious diseases such as EVA71. Copyright © 2020 American Society for Microbiology.Imipenem/relebactam (I/R) is a recently developed carbapenem/beta-lactamase inhibitor combination agent that can overcome carbapenem resistance, which has now emerged in Escherichia coli, including sequence type 131 (ST131) and its fluoroquinolone-resistant H30R subclone, the leading cause of extra-intestinal E. coli infections globally. To clarify the likely utility of I/R for carbapenem-resistant (CR) E. coli infections in the U.S. we characterized 203 recent CR clinical E. coli isolates from across the U.S. (years 2002-2017) for phylogroup, clonal group (including ST131, H30R, and the CTX-M-15-associated H30Rx subset within H30R), relevant beta-lactamase genes, and broth microdilution MICs for I/R and 11 comparator agents. Overall, I/R was highly active (89% susceptible), more so than all comparators except tigecycline and colistin (both, 99% susceptible). I/R's activity varied significantly in relation to phylogroup, clonal background, resistance genotype, and region it was greatest among phylogroup B2, ST131-H30R, H30Rx, Klebsiella pneumoniae carbapenemase (KPC)-positive, and northeast U.S. isolates, and lowest among phylogroup C, New Delhi metallo-β-lactamase (NDM)-positive, and southeast U.S. isolates. Relebactam improved imipenem's activity against CR isolates within each phylogroup - especially groups A, B1, and B2 - and particularly against isolates containing KPC. I/R remained substantially active against isolates co-resistant to comparator agents, albeit somewhat less so than against the corresponding susceptible isolates. These findings suggest that I/R should be useful for treating most CR E. coli infections in the U.S., largely independent of co-resistance, although this likely will vary in relation to the local prevalence of specific E. coli lineages and carbapenem resistance mechanisms. This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.The new complexes [Zn(ITZ)2Cl2] (1) and [Zn(ITZ)2(OH)2] (2) were synthetized by a reaction of itraconazole with their respective zinc salts under reflux. These Zn-ITZ complexes were characterized by elemental analyses, molar conductivity, mass spectrometry, 1H and 13C1H nuclear magnetic resonance, UV-vis and infrared spectroscopies. The antiparasitic and antifungal activity of Zn-ITZ complexes was evaluated against three protozoans of medical importance, Leishmania amazonensis, Trypanosoma cruzi and Toxoplasma gondii, and two fungi, Sporothrix brasiliensis and Sporothrix schenckii The Zn-ITZ complexes exhibited a broad spectrum of action, with antiparasitic and antifungal activity in low concentrations. The strategy of combining zinc with ITZ was efficient to enhance ITZ activity, since Zn-ITZ-complexes were more active than the azole alone. This study opens perspectives for future applications of these Zn-ITZ-complexes in the treatment of parasitic diseases and sporotrichosis. Copyright © 2020 American Society for Microbiology.Type I and III IFNs play diverse roles in bacterial infections, being protective for some but deleterious for others. Using RNA-sequencing transcriptomics we investigated lung gene expression responses to Bordetella pertussis infection in adult mice, revealing that type I and III IFN pathways may play an important role in promoting inflammatory responses. In B. pertussis-infected mice, lung type I/III IFN responses correlated with increased proinflammatory cytokine expression and with lung inflammatory pathology. JPH203 in vitro In mutant mice with increased type I IFN receptor (IFNAR) signaling, B. pertussis infection exacerbated lung inflammatory pathology, whereas knockout mice with defects in type I IFN signaling had lower levels of lung inflammation than wild-type mice. Curiously, B. pertussis-infected IFNAR1 knockout mice had wild-type levels of lung inflammatory pathology. However, in response to infection these mice had increased levels of type III IFN expression, neutralization of which reduced lung inflammation. In support of this finding, B. pertussis-infected mice with a knockout mutation in the type III IFN receptor (IFNLR1) and double IFNAR1/IFNLR1 knockout mutant mice had reduced lung inflammatory pathology compared with that in wild-type mice, indicating that type III IFN exacerbates lung inflammation. In marked contrast, infant mice did not upregulate type I or III IFNs in response to B. pertussis infection and were protected from lethal infection by increased type I IFN signaling. These results indicate age-dependent effects of type I/III IFN signaling during B. pertussis infection and suggest that these pathways represent targets for therapeutic intervention in pertussis. Copyright © 2020 by The American Association of Immunologists, Inc.CRISPR/Cas9 technologies have revolutionized our understanding of gene function in complex biological settings, including T cell immunology. Current CRISPR-mediated gene editing strategies in T cells require in vitro stimulation or culture that can both preclude the study of unmanipulated naive T cells and alter subsequent differentiation. In this study, we demonstrate highly efficient gene editing within uncultured primary naive murine CD8+ T cells by electroporation of recombinant Cas9/sgRNA ribonucleoprotein immediately prior to in vivo adoptive transfer. Using this approach, we generated single and double gene knockout cells within multiple mouse infection models. Strikingly, gene deletion occurred even when the transferred cells were left in a naive state, suggesting that gene deletion occurs independent of T cell activation. Finally, we demonstrate that targeted mutations can be introduced into naive CD8+ T cells using CRISPR-based homology-directed repair. This protocol thus expands CRISPR-based gene editing approaches beyond models of robust T cell activation to encompass both naive T cell homeostasis and models of weak activation, such as tolerance and tumor models.
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