Genome-wide fitness analysis of reveals mutants are attenuated due to iron restriction .

is a globally disseminated pathogen that is the cause of over 100 million infections per year. The resulting diseases are dependent upon host susceptibility and the infecting serovar. As serovar Typhimurium induces a typhoid-like disease in mice, this model has been used extensively to illuminate various aspects of infection and host responses.

A Review of Antibacterial Candidates with New Modes of Action.

There is a lack of new antibiotics to combat drug-resistant bacterial infections that increasingly threaten global health. The current pipeline of clinical-stage antimicrobials is primarily populated by "new and improved" versions of existing antibiotic classes, supplemented by several novel chemical scaffolds that act on traditional targets. The lack of fresh chemotypes acting on previously unexploited targets (the "holy grail" for new antimicrobials due to their scarcity) is particularly unfortunate as these offer the greatest opportunity for innovative breakthroughs to overcome existing resistance.

Microbial Primer: Transposon directed insertion site sequencing (TraDIS): A high throughput method for linking genotype to phenotype.

Genetic screens are a key tool for linking phenotype and genotype. Transposon mutagenesis was one of the first genetic methodologies to associate genetic loci with phenotypes. The advent of next-generation sequencing transformed the use of this technique allowing rapid interrogation of whole genomes for genes that correlate with phenotype.

A multiomic approach to defining the essential genome of the globally important pathogen Corynebacterium diphtheriae.

Diphtheria is a respiratory disease caused by Corynebacterium diphtheriae. While the toxin-based vaccine has helped control outbreaks of the disease since the mid-20th century there has been an increase in cases in recent years, including systemic infections caused by non-toxigenic C. diphtheriae strains.

Plasmids Can Shift Bacterial Morphological Response against Antibiotic Stress.

Bacterial cell filamentation is a morphological change wherein cell division is blocked, which can improve bacterial survival under unfavorable conditions (e.g., antibiotic stress that causes DNA damage).

Transposon-Directed Insertion-Site Sequencing Reveals Glycolysis Gene as Part of the HO Defense Mechanisms in .

Hydrogen peroxide (HO) is a common effector of defense mechanisms against pathogenic infections. However, bacterial factors involved in HO tolerance remain unclear. Here we used transposon-directed insertion-site sequencing (TraDIS), a technique allowing the screening of the whole genome, to identify genes implicated in HO tolerance in .

LI-Detector: a Method for Curating Ordered Gene-Replacement Libraries.

In recent years the availability of genome sequence information has grown logarithmically resulting in the identification of a plethora of uncharacterized genes. To address this gap in functional annotation, many high-throughput screens have been devised to uncover novel gene functions. Gene-replacement libraries are one such tool that can be screened in a high-throughput way to link genotype and phenotype and are key community resources.

Loss of YhcB results in dysregulation of coordinated peptidoglycan, LPS and phospholipid synthesis during Escherichia coli cell growth.

The cell envelope is essential for viability in all domains of life. It retains enzymes and substrates within a confined space while providing a protective barrier to the external environment. Destabilising the envelope of bacterial pathogens is a common strategy employed by antimicrobial treatment.

DpaA Detaches Braun's Lipoprotein from Peptidoglycan.

Gram-negative bacteria have a unique cell envelope with a lipopolysaccharide-containing outer membrane that is tightly connected to a thin layer of peptidoglycan. The tight connection between the outer membrane and peptidoglycan is needed to maintain the outer membrane as an impermeable barrier for many toxic molecules and antibiotics. such as covalently attach the abundant outer membrane-anchored lipoprotein Lpp (Braun's lipoprotein) to tripeptides in peptidoglycan, mediated by the transpeptidases LdtA, LdtB, and LdtC.

Pathogenic Differences of Type 1 Restriction-Modification Allele Variants in Experimental Meningitis.

meningoencephalitis has a mortality rate of up to 50% and neurofunctional sequelae are common. Type I restriction-modification systems (RMS) are capable of adding methyl groups to the host genome. Some contain multiple sequence recognition () genes that recombine, resulting in distinct DNA methylation patterns and patterns of gene expression.

The Essential Genome of K-12.

Transposon-directed insertion site sequencing (TraDIS) is a high-throughput method coupling transposon mutagenesis with short-fragment DNA sequencing. It is commonly used to identify essential genes. Single gene deletion libraries are considered the gold standard for identifying essential genes.