Next-generation humanized NSG-SGM3 mice are highly susceptible to infection.

Humanized hemato-lymphoid system mice, or humanized mice, emerged in recent years as a promising model to study the course of infection of human-adapted or human-specific pathogens. Though infects and colonizes a variety of species, it has nonetheless become one of the most successful human pathogens of our time with a wide armory of human-adapted virulence factors. Humanized mice showed increased vulnerability to compared to wild type mice in a variety of clinically relevant disease models.

The Old Yellow Enzyme OfrA Fosters Survival Affecting Thiol-Dependent Redox Homeostasis.

Old yellow enzymes (OYEs) are widely found in the bacterial, fungal, and plant kingdoms but absent in humans and have been used as biocatalysts for decades. However, OYEs' physiological function in bacterial stress response and infection situations remained enigmatic. As a pathogen, the Gram-positive bacterium adapts to numerous stress conditions during pathogenesis.

Novel 2,4-disubstituted quinazoline analogs as antibacterial agents with improved cytotoxicity profile: Optimization of the 2,4-substituents.

The emergence of bacterial resistance has triggered a multitude of efforts to develop new antibacterial agents. There are many compounds in literature that were reported as potent antibacterial agents, however, they lacked the required safety to mammalian cells or no clear picture about their toxicity profile was presented. Inspired by discovered hit from our in-house library and by previously reported 2,4-diaminosubstituted quinazolines, we describe the design and synthesis of novel 2,4-disubstituted-thioquinazolines (3-13 and 36), 2-thio-4-amino substituted quinazolines (14-33) and 6-substituted 2,4-diamonsubstituted quinazolines (37-39).

Transcriptome Data and Metabolic Modelling Investigate the Interplay of Ser/Thr Kinase PknB, Its Phosphatase Stp, the Regulon and the Operon for Metabolic Adaptation.

Serine/threonine kinase PknB and its corresponding phosphatase Stp are important regulators of many cell functions in the pathogen Genome-scale gene expression data of strain NewHG (sigB) elucidated their effect on physiological functions. Moreover, metabolic modelling from these data inferred metabolic adaptations. We compared wild-type to deletion strains lacking , or both.

Natural Products Repertoire of the Red Sea.

Marine natural products have achieved great success as an important source of new lead compounds for drug discovery. The Red Sea provides enormous diversity on the biological scale in all domains of life including micro- and macro-organisms. In this review, which covers the literature to the end of 2019, we summarize the diversity of bioactive secondary metabolites derived from Red Sea micro- and macro-organisms, and discuss their biological potential whenever applicable.

Dual-tail arylsulfone-based benzenesulfonamides differently match the hydrophobic and hydrophilic halves of human carbonic anhydrases active sites: Selective inhibitors for the tumor-associated hCA IX isoform.

The synthesis and characterization of two new sets of arylsulfonehydrazone benzenesulfonamides (4a-4i with phenyl tail and 4j-4q with tolyl tail) are reported. The compounds were designed according to a dual-tails approach to modulate the interactions of the ligands portions at the outer rim of both hydrophobic and hydrophilic active site halves of human isoforms of carbonic anhydrase (CA, EC 4.2.

Kullback Leibler divergence in complete bacterial and phage genomes.

The amino acid content of the proteins encoded by a genome may predict the coding potential of that genome and may reflect lifestyle restrictions of the organism. Here, we calculated the Kullback-Leibler divergence from the mean amino acid content as a metric to compare the amino acid composition for a large set of bacterial and phage genome sequences. Using these data, we demonstrate that (i) there is a significant difference between amino acid utilization in different phylogenetic groups of bacteria and phages; (ii) many of the bacteria with the most skewed amino acid utilization profiles, or the bacteria that host phages with the most skewed profiles, are endosymbionts or parasites; (iii) the skews in the distribution are not restricted to certain metabolic processes but are common across all bacterial genomic subsystems; (iv) amino acid utilization profiles strongly correlate with GC content in bacterial genomes but very weakly correlate with the G+C percent in phage genomes.

A Degradome-Based Polymerase Chain Reaction to Resolve the Potential of Environmental Samples for 2,4-Dichlorophenol Biodegradation.

A clean way to overcome environmental pollution is biodegradation. In this perspective, at the intersection of biodegradation and metagenomics, the degradome is defined as the totality of genes related to the biodegradation of a certain compound. It includes the genetic elements from both culturable and uncultured microorganisms.