Bax is a Bcl-2 protein critical for apoptosis induction. In healthy cells, Bax is mostly a monomeric, cytosolic protein, while upon apoptosis initiation it inserts into the outer mitochondrial membrane, oligomerizes, and forms pores that release proapoptotic factors like Cytochrome c into the cytosol. The structures of active Bax and its homolog Bak are only partially understood and the topology of the proteins with respect to the membrane bilayer is controversially described in the literature. Here, we systematically review and examine the protein-membrane, protein-water, and protein-protein contacts of the nine helices of active Bax and Bak, and add a new set of topology data obtained by fluorescence and EPR methods. We conclude based on the consistent part of the datasets that the core/dimerization domain of Bax (Bak) is water exposed with only helices 4 and 5 in membrane contact, whereas the piercing/latch domain is in peripheral membrane contact, with helix 9 being transmembrane. Among the available structural models, those considering the dimerization/core domain at the rim of a toroidal pore are the most plausible to describe the active state of the proteins, although the structural flexibility of the piercing/latch domain does not allow unambiguous discrimination between the existing models.

In spring 2021, an increasing number of infections was observed caused by the hitherto rarely described SARS-CoV-2 variant A.27 in south-west Germany. From December 2020 to June 2021 this lineage has been detected in 31 countries. Phylogeographic analyses of A.27 sequences obtained from national and international databases reveal a global spread of this lineage through multiple introductions from its inferred origin in Western Africa. Variant A.27 is characterized by a mutational pattern in the spike gene that includes the L18F, L452R and N501Y spike amino acid substitutions found in various variants of concern but lacks the globally dominant D614G. Neutralization assays demonstrate an escape of A.27 from convalescent and vaccine-elicited antibody-mediated immunity. Moreover, the therapeutic monoclonal antibody Bamlanivimab and partially the REGN-COV2 cocktail fail to block infection by A.27. Our data emphasize the need for continued global monitoring of novel lineages because of the independent evolution of new escape mutations.

Vancomycin-resistant E. faecium (VRE) are an important cause of nosocomial infections, which are rapidly transmitted in hospitals. To identify possible transmission routes, we applied combined genomics and contact-network modeling to retrospectively evaluate routine VRE screening data generated by the infection control program of a hemato-oncology unit. Over 1 year, a total of 111 VRE isolates from 111 patients were collected by anal swabs in a tertiary care hospital in Southern Germany. All isolated VRE were whole-genome sequenced, followed by different in-depth bioinformatics analyses including genotyping and determination of phylogenetic relations, aiming to evaluate a standardized workflow. Patient movement data were used to overlay sequencing data to infer transmission events and strain dynamics over time. A predominant clone harboring vanB and exhibiting genotype ST117/CT469 (n = 67) was identified. Our comprehensive combined analyses suggested intra-hospital spread, especially of clone ST117/CT469, despite of extensive screening, single room placement, and contact isolation. A new interactive tool to visualize these complex data was designed. Furthermore, a patient-contact network-modeling approach was developed, which indicates both the periodic import of the clone into the hospital and its spread within the hospital due to patient movements. The analyzed spread of VRE was most likely due to placement of patients in the same room prior to positivity of screening. We successfully demonstrated the added value for this combined strategy to extract well-founded knowledge from interdisciplinary data sources. The combination of patient-contact modeling and high-resolution typing unraveled the transmission dynamics within the hospital department and, additionally, a constant VRE influx over time.

Summary The ongoing pandemic caused by SARS-CoV-2 emphasizes the importance of genomic surveillance to understand the evolution of the virus, to monitor the viral population, and plan epidemiological responses. Detailed analysis, easy visualization, and intuitive filtering of the latest viral sequences are powerful for this purpose. We present CovRadar, a tool for genomic surveillance of the SARS-CoV-2 Spike protein. CovRadar consists of an analytical pipeline and a web application that enable the analysis and visualization of hundreds of thousands sequences. First, CovRadar extracts the regions of interest using local alignment, then builds a multiple sequence alignment, infers variants and consensus, and finally presents the results in an interactive app, making accessing and reporting simple, flexible and fast. Availability and implementation CovRadar is freely accessible at https://covradar.net, its open-source code is available at https://gitlab.com/dacs-hpi/covradar. Supplementary information Supplementary data are available at Bioinformatics online.

The ongoing pandemic caused by SARS-CoV-2 emphasizes the importance of molecular surveillance to understand the evolution of the virus and to monitor and plan the epidemiological responses. Quick analysis, easy visualization and convenient filtering of the latest viral sequences are essential for this purpose. We present CovRadar, a tool for molecular surveillance of the Corona spike protein. The spike protein contains the receptor binding domain (RBD) that is used as a target for most vaccine candidates. CovRadar consists of a workflow pipeline and a web application that enable the analysis and visualization of over 250,000 sequences. First, CovRadar extracts the regions of interest using local alignment, then builds a multiple sequence alignment, infers variants, consensus sequences and phylogenetic trees and finally presents the results in an interactive PDF-like app, making reporting fast, easy and flexible. CovRadar is freely accessible at https://covradar.net, its open-source code is available at https://gitlab.com/dacs-hpi/covradar.

In spring 2021, an increasing number of infections was observed caused by the hitherto rarely described SARS-CoV-2 variant A.27 in south-west Germany. From December 2020 to June 2021 this lineage has been detected in 31 countries. Phylogeographic analyses of A.27 sequences obtained from national and international databases reveal a global spread of this lineage through multiple introductions from its inferred origin in Western Africa. Variant A.27 is characterized by a mutational pattern in the spike gene that includes the L18F, L452R and N501Y spike amino acid substitutions found in various variants of concern but lacks the globally dominant D614G. Neutralization assays demonstrated an escape of A.27 from convalescent and vaccine-elicited antibody-mediated immunity. Moreover, the therapeutic monoclonal antibody Bamlanivimab and partially the REGN-COV2 cocktail failed to block infection by A.27. Our data emphasize the need for continued global monitoring of novel lineages because of the independent evolution of new escape mutations.

Monkeypox (Mpox) is mutating at an exceptional rate for a DNA virus and its global spread is concerning, making genomic surveillance a necessity. With MpoxRadar, we provide an interactive dashboard to track virus variants on mutation level worldwide. MpoxRadar allows users to select among different genomes as reference for comparison. The occurrence of mutation profiles based on the selected reference is indicated on an interactive world map that shows the respective geographic sampling site in customizable time ranges to easily follow the frequency or trend of defined mutations. Furthermore, the user can filter for specific mutations, genes, countries, genome types, and sequencing protocols and download the filtered data directly from MpoxRadar. On the server, we automatically download all Mpox genomes and metadata from the National Center for Biotechnology Information (NCBI) on a daily basis, align them with the different reference genomes, generate mutation profiles, which are stored and linked to the available metainformation in a database. This makes MpoxRadar a practical tool for the genomic survaillance of Mpox, supporting users with limited computational resources. MpoxRadar is open-source and freely accessible at https://MpoxRadar.net.

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