Designing and identifying β-hairpin peptide macrocycles with antibiotic potential.

Peptide macrocycles are a rapidly emerging class of therapeutic, yet the design of their structure and activity remains challenging. This is especially true for those with β-hairpin structure due to weak folding properties and a propensity for aggregation. Here, we use proteomic analysis and common antimicrobial features to design a large peptide library with macrocyclic β-hairpin structure.

Discovery of Antimicrobial Peptide Macrocycles Through Bacterial Display.

Peptide macrocycles exhibit great ability to inhibit bacterial growth making them a promising new avenue for antimicrobial discovery. Surface Localized Antimicrobial Display (SLAY) is a platform allowing the high-throughput screening of large peptide libraries of diverse length, composition, or structure for their antimicrobial activity, including macrocyclic peptides cyclized through disulfide bonding. Here we describe the procedure for the design and construction of a SLAY peptide library and the process for screening that library for antimicrobial potential.

Single-molecule nanopore sequencing reveals extreme target copy number heterogeneity in arylomycin-resistant mutants.

Tandem gene amplification is a frequent and dynamic source of antibiotic resistance in bacteria. Ongoing expansions and contractions of repeat arrays during population growth are expected to manifest as cell-to-cell differences in copy number (CN). As a result, a clonal bacterial culture could comprise subpopulations of cells with different levels of antibiotic sensitivity that result from variable gene dosage.

A systematic analysis of the beta hairpin motif in the Protein Data Bank.

The beta hairpin motif is a ubiquitous protein structural motif that can be found in molecules across the tree of life. This motif, which is also popular in synthetically designed proteins and peptides, is known for its stability and adaptability to broad functions. Here, we systematically probe all 49,000 unique beta hairpin substructures contained within the Protein Data Bank (PDB) to uncover key characteristics correlated with stable beta hairpin structure, including amino acid biases and enriched interstrand contacts.

TsrA Regulates Virulence and Intestinal Colonization in .

Pathogenic strains of require careful regulation of horizontally acquired virulence factors that are largely located on horizontally acquired genomic islands (HAIs). While TsrA, a -specific protein, is known to regulate the critical HAI virulence genes and , its broader function throughout the genome is unknown. Here, we find that deletion of results in genomewide expression patterns that heavily correlate with those seen upon deletion of , a widely conserved bacterial protein that regulates virulence.

A Comprehensive Coexpression Network Analysis in Vibrio cholerae.

Research into the evolution and pathogenesis of has benefited greatly from the generation of high-throughput sequencing data to drive molecular analyses. The steady accumulation of these data sets now provides a unique opportunity for hypothesis generation via coexpression analysis. Here, we leverage all published RNA sequencing data, in combination with select data from other platforms, to generate a gene coexpression network that validates known gene interactions and identifies novel genetic partners across the entire genome.

Protein Aggregation is Associated with Desiccation Tolerance.

Desiccation tolerance has been implicated as an important characteristic that potentiates the spread of the bacterial pathogen on dry surfaces. Here we explore several factors influencing desiccation survival of . At the macroscale level, we find that desiccation tolerance is influenced by cell density and growth phase.

Influenza passaging annotations: what they tell us and why we should listen.

Influenza databases now contain over 100,000 worldwide sequence records for strains influenza A(H3N2) and A(H1N1). Although these data facilitate global research efforts and vaccine development practices, they also represent a stumbling block for researchers because of their confusing and heterogeneous annotation. Unclear passaging annotations are particularly concerning given the recent work highlighting the presence and risk of false adaptation signals introduced by cell passaging of viral isolates.