The NS1 protein of influenza B virus binds 5'-triphosphorylated dsRNA to suppress RIG-I activation and the host antiviral response.

Influenza A and B viruses overcome the host antiviral response to cause a contagious and often severe human respiratory disease. Here, integrative structural biology and biochemistry studies on non-structural protein 1 of influenza B virus (NS1B) reveal a previously unrecognized viral mechanism for innate immune evasion. Conserved basic groups of its C-terminal domain (NS1B-CTD) bind 5'triphosphorylated double-stranded RNA (5'-ppp-dsRNA), the primary pathogen-associated feature that activates the host retinoic acid-inducible gene I protein (RIG-I) to initiate interferon synthesis and the cellular antiviral response.

Different Conformations Revealed by NMR Underlie Resistance to Ceftazidime/Avibactam and Susceptibility to Meropenem and Imipenem among D179Y Variants of KPC β-Lactamase.

β-Lactamase-mediated resistance to ceftazidime-avibactam (CZA) is a serious limitation in the treatment of Gram-negative bacteria harboring Klebsiella pneumoniae carbapenemase (KPC). Herein, the basis of susceptibility to carbapenems and resistance to ceftazidime (CAZ) and CZA of the D179Y variant of KPC-2 and -3 was explored. First, we determined that resistance to CZA in a laboratory strain of Escherichia coli DH10B was not due to increased expression levels of the variant enzymes, as demonstrated by reverse transcription PCR (RT-PCR).

Structural Comparisons of Cefotaximase (CTX-M-ase) Sub Family 1.

The cefotaximase or CTX-M, family of serine-β-lactamases represents a significant clinical concern due to the ability for these enzymes to confer resistance to a broad array of β-lactam antibiotics an inhibitors. This behavior lends CTX-M-ases to be classified as extended spectrum β-lactamases (ESBL). Across the family of CTX-M-ases most closely related to CTX-M-1, the structures of CTX-M-15 with a library of different ligands have been solved and serve as the basis of comparison within this review.

Carbapenem Use Is Driving the Evolution of Imipenemase 1 Variants.

Metallo-β-lactamases (MBLs) are a growing clinical threat because they inactivate nearly all β-lactam-containing antibiotics, and there are no clinically available inhibitors. A significant number of variants have already emerged for each MBL subfamily. To understand the evolution of imipenemase (IMP) genes () and their clinical impact, 20 clinically derived IMP-1 like variants were obtained using site-directed mutagenesis and expressed in a uniform genetic background in strain DH10B.

Mapping protein-polymer conformations in bioconjugates with atomic precision.

Rational design of protein-polymer bioconjugates is hindered by limited experimental data and mechanistic understanding on interactions between the two. In this communication, nuclear magnetic resonance (NMR) paramagnetic relaxation enhancement (PRE) reports on distances between paramagnetic spin labels and NMR active nuclei, informing on the conformation of conjugated polymers. H/N-heteronuclear single quantum coherence (HSQC) NMR spectra were collected for ubiquitin (Ub) modified with block copolymers incorporating spin labels at different positions along their backbone.

An integrated biophysical approach to discovering mechanisms of NDM-1 inhibition for several thiol-containing drugs.

Due to the rapid proliferation of antibiotic-resistant pathogenic bacteria, known as carbapenem-resistant enterobacteriaceae, the efficacy of β-lactam antibiotics is threatened. β-lactam antibiotics constitute over 50% of the available antibiotic arsenal. Recent efforts have been focused on developing inhibitors to these enzymes.

A Single Salt Bridge in VIM-20 Increases Protein Stability and Antibiotic Resistance under Low-Zinc Conditions.

To understand the evolution of Verona integron-encoded metallo-β-lactamase (VIM) genes () and their clinical impact, microbiological, biochemical, and structural studies were conducted. Forty-five clinically derived VIM variants engineered in a uniform background and expressed in afforded increased resistance toward all tested antibiotics; the variants belonging to the VIM-1-like and VIM-4-like families exhibited higher MICs toward five out of six antibiotics than did variants belonging to the widely distributed and clinically important VIM-2-like family. Generally, maximal MIC increases were observed when cephalothin and imipenem were tested.

Influence of substrates and inhibitors on the structure of carbapenemase-2.

Unlabelled: The hydrolysis of last resort carbapenem antibiotics by carbapenemase-2 (KPC-2) presents a significant danger to global health. Combined with horizontal gene transfer, the emergence KPC-2 threatens to quickly expand carbapenemase activity to ever increasing numbers of pathogens. Our understanding of KPC-2 has greatly increased over the past decade thanks, in great part, to 20 crystal structures solved by groups around the world.

H, C, and N backbone resonance assignments for KPC-2, a class A serine-β-lactamase.

The ever-increasing occurrence of antibiotic resistance presents a major threat to public health. Specifically, resistance conferred by β-lactamases places the efficacy of currently available antibiotics at risk. Klebsiella pneumoniae carbapenemase-2 (KPC-2) is a β-lactamase that enables carbapenem resistance and represents a clear and present danger to global public health.