A Structural Systems Biology Approach to High-Risk CG23 Klebsiella pneumoniae.

Klebsiella pneumoniae is a leading cause of antibiotic-resistant-associated deaths in the world. Here, we report the deposition of 14 structures of enzymes from both the core and accessory genomes of sequence type 23 (ST23) K1 hypervirulent K. pneumoniae.

Bioengineered peptibodies as blockers of ion channels.

We engineered and produced an ion channel blocking peptibody, that targets the acetylcholine-activated inwardly rectifying potassium current (I). Peptibodies are chimeric proteins generated by fusing a biologically active peptide with the fragment crystallizable (Fc) region of the human immunoglobulin G (IgG). The I blocking peptibody was engineered as a fusion between the human IgG1 Fc fragment and the I inhibitor tertiapinQ (TP), a 21-amino acid synthetic peptidotoxin, originally isolated from the European honey bee venom.

A Novel Soluble ACE2 Protein Provides Lung and Kidney Protection in Mice Susceptible to Lethal SARS-CoV-2 Infection.

Background: Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) uses full-length angiotensin converting enzyme 2 (ACE2) as a main receptor to enter target cells. The goal of this study was to demonstrate the preclinical efficacy of a novel soluble ACE2 protein with increased duration of action and binding capacity in a lethal mouse model of COVID-19.

Methods: A human soluble ACE2 variant fused with an albumin binding domain (ABD) was linked a dimerization motif hinge-like 4-cysteine dodecapeptide (DDC) to improve binding capacity to SARS-CoV-2.

The spermidine acetyltransferase SpeG regulates transcription of the small RNA rprA.

Spermidine N-acetyltransferase (SpeG) acetylates and thus neutralizes toxic polyamines. Studies indicate that SpeG plays an important role in virulence and pathogenicity of many bacteria, which have evolved SpeG-dependent strategies to control polyamine concentrations and survive in their hosts. In Escherichia coli, the two-component response regulator RcsB is reported to be subject to Nε-acetylation on several lysine residues, resulting in reduced DNA binding affinity and reduced transcription of the small RNA rprA; however, the physiological acetylation mechanism responsible for this behavior has not been fully determined.

Crystal structure of nonphosphorylated receiver domain of the stress response regulator RcsB from Escherichia coli.

RcsB, the transcription-associated response regulator of the Rcs phosphorelay two-component signal transduction system, activates cell stress responses associated with desiccation, cell wall biosynthesis, cell division, virulence, biofilm formation, and antibiotic resistance in enteric bacterial pathogens. RcsB belongs to the FixJ/NarL family of transcriptional regulators, which are characterized by a highly conserved C-terminal DNA-binding domain. The N-terminal domain of RcsB belongs to the family of two-component receiver domains.