Vaccines and therapeutics are urgently needed for the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we screen human monoclonal antibodies (mAb) targeting the receptor binding domain (RBD) of the viral spike protein via antibody library constructed from peripheral blood mononuclear cells of a convalescent patient. The CT-P59 mAb potently neutralizes SARS-CoV-2 isolates including the D614G variant without antibody-dependent enhancement effect. Complex crystal structure of CT-P59 Fab/RBD shows that CT-P59 blocks interaction regions of RBD for angiotensin converting enzyme 2 (ACE2) receptor with an orientation that is notably different from previously reported RBD-targeting mAbs. Furthermore, therapeutic effects of CT-P59 are evaluated in three animal models (ferret, hamster, and rhesus monkey), demonstrating a substantial reduction in viral titer along with alleviation of clinical symptoms. Therefore, CT-P59 may be a promising therapeutic candidate for COVID-19.
Antimicrobial resistance and multidrug resistance are slower-moving pandemics than the fast-spreading coronavirus disease 2019; however, they have potential to cause a much greater threat to global health. Here, we report a clustered regularly interspaced short palindromic repeats (CRISPR)-mediated surface-enhanced Raman scattering (SERS) assay for multidrug-resistant (MDR) bacteria. This assay was developed via a synergistic combination of the specific gene-recognition ability of the CRISPR system, superb sensitivity of SERS, and simple separation property of magnetic nanoparticles. This assay detects three multidrug-resistant (MDR) bacteria, species Staphylococcus aureus, Acinetobacter baumannii, and Klebsiella pneumoniae, without purification or gene amplification steps. Furthermore, MDR A. baumannii-infected mice were successfully diagnosed using the assay. Finally, we demonstrate the on-site capture and detection of MDR bacteria through a combination of the three-dimensional nanopillar array swab and CRISPR-mediated SERS assay. This method may prove effective for the accurate diagnosis of MDR bacterial pathogens, thus preventing severe infection by ensuring appropriate antibiotic treatment.
Acinetobacter baumannii is a highly potent nosocomial pathogen that is associated with increased in-hospital mortality. Here, we investigated the changes in molecular characteristics of carbapenem-resistant A. baumannii (CRAB) isolated from the blood samples of patients admitted to a tertiary hospital in South Korea from January 2009 to July 2015. Whole genome sequencing using the Illumina MiSeq platform and multi-locus sequence typing (MLST) were performed for 98 CRAB clinical isolates. In silico analyses for the prediction of antimicrobial resistance and virulence factor genes were performed. Plasmid sequences, including complete forms, were reconstructed from the sequence reads. Epidemiologic data were collected from the hospital database. MLST using the Oxford scheme revealed 10 sequence types of CRAB, of which ST191 was the dominant type (n = 59). Although bla OXA-23 was shared by most analysed strains, the compositions of antimicrobial resistance determinants differed among sequence types. ST447 and ST451/ST1809 with a few resistance genes were isolated during the later years of the study period. The number of virulence genes increased, while that of ST191 did not change significantly over the investigation period. Intriguingly MLST types, compositions of antimicrobial resistance genes, and virulence genes had no association with clinical outcomes of CRAB bacteraemia. In conclusion, active changes in or accumulations of antimicrobial resistance determinants and virulence genes in CRAB were not observed during the research period. Molecular characteristics of CRAB had no association with clinical outcomes of CRAB bacteraemia.
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