A rationally designed antimicrobial peptide from structural and functional insights of translation initiation factor 1.

A significant increase of hospital-acquired bacterial infections during the COVID-19 pandemic has become an urgent medical problem. is an urgent antibiotic-resistant bacterial pathogen and a leading causative agent of nosocomial infections. The increasing recurrence of infection and antibiotic resistance in has led to an unmet need for the discovery of new compounds distinctly different from present antimicrobials, while antimicrobial peptides as promising alternatives to conventional antibiotics have attracted growing interest recently.

Rational Design of an Antimicrobial Peptide Based on Structural Insight into the Interaction of Initiation Factor 1 with Its Cognate 30S Ribosomal Subunit.

Bacterial infections continue to represent a major worldwide health hazard following the emergence of drug-resistant pathogenic strains. is an opportunistic pathogen causing nosocomial infections with increased morbidity and mortality. The increasing antibiotic resistance in has led to an unmet need for discovery of new antibiotic candidates.

Two Forms of Tyrosyl-tRNA Synthetase from : Characterization and Discovery of Inhibitory Compounds.

is a multidrug-resistant (MDR) pathogen and a causative agent of both nosocomial and community-acquired infections. The genes (S and Z) encoding both forms of tyrosyl-tRNA synthetase (TyrRS-S and TyrRS-Z) were cloned and the resulting proteins purified. TyrRS-S and TyrRS-Z were kinetically evaluated and the values for interaction with Tyr, ATP, and tRNA were 172, 204, and 1.

Glutaminyl-tRNA Synthetase from Pseudomonas aeruginosa: Characterization, structure, and development as a screening platform.

Pseudomonas aeruginosa has a high potential for developing resistance to multiple antibiotics. The gene (glnS) encoding glutaminyl-tRNA synthetase (GlnRS) from P. aeruginosa was cloned and the resulting protein characterized.

Lysyl-tRNA Synthetase from : Characterization and Identification of Inhibitory Compounds.

is an opportunistic pathogen that causes nosocomial infections and has highly developed systems for acquiring resistance against numerous antibiotics. The gene (S) encoding lysyl-tRNA synthetase (LysRS) was cloned and overexpressed, and the resulting protein was purified to 98% homogeneity. LysRS was kinetically evaluated, and the values for the interaction with lysine, adenosine triphosphate (ATP), and tRNA were determined to be 45.

Discovery and Characterization of Chemical Compounds That Inhibit the Function of Aspartyl-tRNA Synthetase from Pseudomonas aeruginosa.

Pseudomonas aeruginosa, an opportunistic pathogen, is highly susceptible to developing resistance to multiple antibiotics. The gene encoding aspartyl-tRNA synthetase (AspRS) from P. aeruginosa was cloned and the resulting protein characterized.

Identification of Chemical Compounds That Inhibit the Function of Histidyl-tRNA Synthetase from Pseudomonas aeruginosa.

Pseudomonas aeruginosa histidyl-tRNA synthetase (HisRS) was selected as a target for antibiotic drug development. The HisRS protein was overexpressed in Escherichia coli and kinetically evaluated. The K values for interaction of HisRS with its three substrates, histidine, ATP, and tRNA, were 37.

Identification and Characterization of a Chemical Compound that Inhibits Methionyl-tRNA Synthetase from Pseudomonas aeruginosa.

Background: Pseudomonas aeruginosa is an opportunistic pathogen problematic in causing nosocomial infections and is highly susceptible to development of resistance to multiple antibiotics. The gene encoding methionyl-tRNA synthetase (MetRS) from P. aeruginosa was cloned and the resulting protein characterized.

Quinazolin-2-ylamino-quinazolin-4-ols as novel non-nucleoside inhibitors of bacterial DNA polymerase III.

High throughput screening led to the discovery of a novel series of quinazolin-2-ylamino-quinazolin-4-ols as a new class of DNA polymerase III inhibitors. The inhibition of chromosomal DNA replication results in bacterial cell death. The synthesis, structure-activity relationships and functional activity are described.

Inhibition of methionyl-tRNA synthetase by REP8839 and effects of resistance mutations on enzyme activity.

REP8839 is a selective inhibitor of methionyl-tRNA synthetase (MetRS) with antibacterial activity against a variety of gram-positive organisms. We determined REP8839 potency against Staphylococcus aureus MetRS and assessed its selectivity for bacterial versus human orthologs of MetRS. The inhibition constant (K(i)) of REP8839 was 10 pM for Staphylococcus aureus MetRS.

Mode of action and biochemical characterization of REP8839, a novel inhibitor of methionyl-tRNA synthetase.

Aminoacyl-tRNA synthetases have attracted interest as essential and novel targets involved in bacterial protein synthesis. REP8839 is a potent inhibitor of MetS, the methionyl-tRNA synthetase in Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), and in Streptococcus pyogenes.

Unbiased whole-genome amplification directly from clinical samples.

Preparation of genomic DNA from clinical samples is a bottleneck in genotyping and DNA sequencing analysis and is frequently limited by the amount of specimen available. We use Multiple Displacement Amplification (MDA) to amplify the whole genome 10,000-fold directly from small amounts of whole blood, dried blood, buccal cells, cultured cells, and buffy coats specimens, generating large amounts of DNA for genetic testing. Genomic DNA was evenly amplified with complete coverage and consistent representation of all genes.

Comprehensive human genome amplification using multiple displacement amplification.

Fundamental to most genetic analysis is availability of genomic DNA of adequate quality and quantity. Because DNA yield from human samples is frequently limiting, much effort has been invested in developing methods for whole genome amplification (WGA) by random or degenerate oligonucleotide-primed PCR. However, existing WGA methods like degenerate oligonucleotide-primed PCR suffer from incomplete coverage and inadequate average DNA size.