ObjectivesIsolates of Pseudomonas aeruginosa from cystic fibrosis (CF) patients are frequently hypermutable due to selection mutants with defects in DNA repair genes such as mutS. Since P. grows a biofilm within the infected CF lung, it is possible that this mode growth enhances mutability organism thereby increasing opportunity derive permanent hypermutators through mutation genes. We have now conducted experiments examine possibility.

The proposed lethal action of daptomycin on Staphylococcusaureus results from the loss K+ and membrane depolarization. However, whether these events alone cause cell death has been questioned. We sought to determine other consequences daptomycin-mediated damage may contribute death. Previously established assays were used evaluate damaging activity at a single time-point 10 min. More detailed time-course experiments also performed kinetics depolarization leakage K+, Mg2+ ATP. inhibition...

Lipid coated liquid crystal droplets have been trapped in a novel trap structure for the on-chip detection of model antimicrobial peptide – Smp43, an α-helical from Scorpion Venom.

XF-73 is a novel porphyrin antibacterial agent previously reported to inhibit range of gram-positive bacterial species, including Staphylococcus aureus. Its mode action unknown. Using S. aureus as model organism we sought examine the basis its activity.The effects on growth and survival SH1000 were investigated by viable count culture absorbance techniques. Inhibition macromolecular synthesis disruption membrane integrity after exposure examined radiolabelling experiments, BacLight...

Slow-growing and non-dividing bacteria exhibit tolerance to many antibiotics. However, membrane-active agents may act against in all growth phases. We sought examine whether the novel porphyrin antibacterial XF-70 XF-73, which have rapid membrane-perturbing activity Staphylococcus aureus, retained antistaphylococcal growth-attenuated cells. The killing kinetics of XF-70, XF-73 various comparator exponential phase cultures S. aureus SH1000 were compared with effects on cells held at 4°C,...

Oxazolidinone and pleuromutilin antibiotics are currently used in the treatment of staphylococcal infections. Although both inhibit protein synthesis have overlapping binding regions on 23S rRNA, potential for cross-resistance between two classes through target site mutations has not been thoroughly examined. Mutants Staphylococcus aureus resistant to linezolid were selected found exhibit tiamulin, a member class antibiotics. However, resistance was unidirectional because mutants S. tiamulin...

The alarming rise in the prevalence of antibiotic resistance among pathogenic bacteria poses a unique challenge for development effective therapeutic agents. Antimicrobial peptides (AMPs) have attracted great deal attention as possible solution to increasing problem antibiotic-resistant bacteria. Marcin-18 was identified from scorpion Mesobuthus martensii at both DNA and protein levels. genomic sequence revealed that marcin-18 coding gene contains phase-I intron with GT-AG splice junction...

The responses of hypermutable Escherichia coli strains to selection with antibiotics having different endogenous resistance potentials were determined. Selections rifampicin or ciprofloxacin at 4 × MIC, i.e. conditions where they act as single target agents against RpoB and GyrA, respectively, demonstrated that some hypermutators generated resistant mutants frequencies up 1000-fold higher than normal strains. Furthermore, individual recovered from hosts often exhibited levels the drugs...

Aim Enterobacterial repetitive intergenic consensus (ERIC) sequence analysis is a powerful tool for epidemiological of bacterial species. This study aimed to determine the genetic relatedness or variability in carbapenem-resistant isolates by species using this technique. Methods A total 111 non-duplicated (CR) Gram-negative bacilli from three-year collection period (2012–2014) were investigated enterobacterial consensus-polymerase chain reaction (ERIC–PCR) four selected hospital...

In Ghana, surveillance efforts on antibiotic resistance so far have not covered carbapenem resistance. this study, our aim was to apply phenotypic and genotypic methods identify characterize carbapenem-resistant (CR) Gram-negative bacteria from the hospital environment in Ghana. A collection of 3840 isolates bacilli infections various clinical specimens screened for by disc diffusion imipenem, meropenem, doripenem. Minimum Inhibitory Concentration (MIC) CR determined E-test three...

Objectives: To develop a novel β-galactosidase leakage assay for Staphylococcus aureus and to evaluate this alongside other simple methods detection of agents that cause membrane damage in staphylococci.

The expression of the positively charged human protein secretory leukocyte protease inhibitor (SLPI) in Escherichia coli causes severe cellular toxicity. After induction SLPI synthesis a high-level-expression strain, SGE61, growth strain is arrested and total RNA rates decline by 60 to 70%. mechanism SLPI-mediated inhibition macromolecular was examined cell-free transcription-translation systems. proved be potent translation vitro. When added reactions at SLPI/mRNA ratios attained during...

Understanding the mechanism of action antimicrobial peptides (AMP) is fundamental to development and design peptide based antimicrobials. Utilizing fast-scan atomic force microscopy (AFM) we detail attack an AMP on both prototypical prokaryotic (DOPC:DOPG) eukaryotic (DOPC:DOPE) model lipid membranes nanoscale in real time. Previously shown have a favourable therapeutic index, study Smp43, with helical-hinge-helical topology isolated from venom North African scorpion Scorpio maurus palmatus....

Determining the mechanism of action antimicrobial peptides (AMPs) is critical if they are to be developed into clinical setting. In recent years high resolution techniques such as atomic force microscopy (AFM) have increasingly been utilised determine AMP on planar lipid bilayers and live bacteria. Here we present biophysical characterisation a prototypical from venom North African scorpion Scorpio maurus palmatus termed Smp24. Smp24 an amphipathic helical peptide containing 24 residues with...

The antibacterial properties of novel quinoline-indole (QI) agents were examined. QI demonstrated potent bactericidal activities against Staphylococcus aureus, killing by lytic and nonlytic mechanisms. S. aureus mutants resistant to a agent (SEP 155342) 118843) arose at frequencies 1.4 x 10(-9) 1.2 10(-8), respectively, selection four times the MICs. Mutants SEP 155342 unstable, but 118843 displayed stable resistance. not cross other inhibitors, including 155342. Addition MIC caused...

Within the last decade, several peptides have been identified according to their ability inhibit growth of microbial pathogens. These antimicrobial (AMPs) are a part innate immune system all living organisms. Many studies on effects prokaryotic microorganisms reported; some these cytotoxic properties although molecular mechanisms underlying activity eukaryotic cells remain poorly understood. Smp24 and Smp43 novel cationic AMPs which were from venom Egyptian scorpion Scorpio maurus palmatus....

Abstract 1,2,3‐benzotriazin‐4(3 H )‐one derivatives have been recognised for their potential application as pesticides and pharmaceuticals new methodologies preparation, starting from readily accessible reagents would therefore be an attractive proposition. A wide range of differently substituted benzamides are available, which provide excellent substrate scaffold the direct C−H functionalization protocols. In this context, herein we report use a Cp*Co(III) catalyst amidation these...

Mutators may present an enhanced risk for the emergence of antibiotic resistance in bacteria during chemotherapy. Using Escherichia coli mutators as a model, we evaluated their ability to develop antibiotics routinely used treatment urinary tract infections (UTIs). Under conditions that simulate therapeutic drug concentrations humans, low-level trimethoprim, gentamicin, and cefotaxime emerged more frequently than normal strains. Resistance trimethoprim both cell types arose from single point...

ABSTRACT The development of resistance to linezolid (LZD) in gram-positive bacteria depends on the mutation a single 23S rRNA gene, followed by homologous recombination and gene conversion other alleles. We sought inhibit this process Staphylococcus aureus using range antibacterial agents, including some that suppress recombination. A model for rapid selection LZD was developed which allowed LZD-resistant mutants with G2576T mutations all five copies following only 5 days subculture....

We sought to identify and characterize new inhibitors of MurA MurZ, which are enzymes involved in the early stages bacterial peptidoglycan synthesis.A library ∼650 000 compounds was screened for Escherichia coli an endpoint assay measuring release inorganic phosphate from phosphoenolpyruvate. Hits were validated by determining concentrations required 50% inhibition (IC(50)) E. MurA/MurZ Staphylococcus aureus. The mode action selected explored examining reversibility inhibition, binding a...