A5073670557- Antibiotic Resistance in Bacteria
- Antimicrobial Resistance in Staphylococcus
- Bacterial biofilms and quorum sensing
- Antimicrobial agents and applications
- Bacterial Genetics and Biotechnology
- Antimicrobial Peptides and Activities
- Microbial Natural Products and Biosynthesis
- RNA and protein synthesis mechanisms
- Bacterial Identification and Susceptibility Testing
- Trace Elements in Health
- Innovations in Medical Education
- Cancer therapeutics and mechanisms
- Pharmaceutical and Antibiotic Environmental Impacts
- RNA modifications and cancer
- Health and Medical Research Impacts
- Clostridium difficile and Clostridium perfringens research
- Antibiotic Use and Resistance
- Synthesis and Catalytic Reactions
- Smart Cities and Technologies
- Nanoparticles: synthesis and applications
- Pigment Synthesis and Properties
- History of Medical Practice
- Click Chemistry and Applications
- Biochemical and Structural Characterization
- Biopolymer Synthesis and Applications
University of Leeds
2011-2022
Abstract Objectives To gain a more detailed understanding of endogenous (mutational) and exogenous (horizontally acquired) resistance to silver in Gram-negative pathogens, with an emphasis on clarifying the genetic bases for resistance. Methods A suite microbiological molecular techniques was employed select characterize several species. Results In Escherichia coli, arose after 6 days exposure silver, consequence two point mutations that were both necessary sufficient phenotype. These...
Antistaphylococcal agents commonly lack activity against Gram-negative bacteria like Escherichia coli owing to the permeability barrier presented by outer membrane and/or action of efflux transporters. When these intrinsic resistance mechanisms are artificially compromised, such almost invariably demonstrate antibacterial Gram negatives. Here we show that this is not case for antibiotic daptomycin, whose target appears be absent from E. and other pathogens.
ObjectivesTo examine several poorly understood or contentious aspects of the antibacterial activity silver (Ag+), including its cidality, mode action, prevalence resistance amongst clinical staphylococcal isolates and propensity for Staphylococcus aureus to develop Ag+ resistance.
Antibiotic resistance hinders the treatment of bacterial infection. To guide effective therapy, clinical microbiology laboratories routinely perform susceptibility testing to determine antibiotic sensitivity an infecting pathogen. This approach relies on assumption that it can reliably distinguish bacteria capable expressing in patients, idea challenged by present study. We report important human pathogen Staphylococcus aureus frequently carries genes have become inactivated (“silenced”)...
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,...
Lantibiotics such as nisin (NIS) are peptide antibiotics that may have a role in the chemotherapy of bacterial infections. A perceived benefit lantibiotics for clinical use is their low propensity to select resistance, although detailed resistance studies with relevant pathogens lacking. Here we examined development NIS Staphylococcus aureus, establishing mutants, including small-colony variants, exhibiting substantial (4- 32-fold) reductions susceptibility could be selected readily....
ABSTRACT Methicillin-resistant Staphylococcus aureus (MRSA) resistant to decolonization agents such as mupirocin and chlorhexidine increases the need for development of alternative molecules. The absence reported severe adverse reactions bacterial resistance polyhexanide makes it an excellent choice a topical antiseptic. In present study, we evaluated in vitro vivo capacity generate strains with reduced susceptibility cross-resistance and/or antibiotics currently used clinic. Here report...
To assess the prevalence of cryptic silver (Ag+) resistance amongst clinical isolates Gram-negative bacteria, and to examine how overt Ag+ becomes activated in such strains.Established methods were used determine susceptibility 444 recent Ag+, evaluate potential for emerge susceptible by spontaneous mutation. The genetic basis was investigated using PCR amplification DNA sequencing.None tested displayed resistance. However, upon challenge, high-level (silver nitrate MIC >128 mg/L) selected...
Resistance to the lantibiotic nisin (NIS) arises readily in Staphylococcus aureus as a consequence of mutations nsaS gene, which encodes sensor kinase NsaRS two-component regulatory system. Here we present series studies establish how these mutational changes result reduced NIS susceptibility. Comparative transcriptomic analysis revealed upregulation regulon NIS-resistant mutant S. versus its otherwise-isogenic progenitor, indicating that resistance prompt gain-of-function NsaS. Two putative...
Background ATP-dependent D-alanine:D-alanine ligase (Ddl) is a part of biochemical machinery involved in peptidoglycan biosynthesis, as it catalyzes the formation terminal D-ala-D-ala dipeptide precursor UDPMurNAc-pentapeptide. Inhibition Ddl prevents bacterial growth, which makes this enzyme an attractive and viable target urgent search novel effective antimicrobial drugs. To address problem relentless increase resistance to known agents we focused our attention discovery ATP-competitive...
Of the thousands of natural product antibiotics discovered to date, only a handful have been developed for treatment bacterial infection. The clinically unexploited majority likely include compounds with untapped potential as antibacterial drugs, and in view ever-growing unmet medical need such agents, warrant systematic re-evaluation. Here we revisit actinorhodins, class that was first reported 70 years ago, but which remains poorly characterized. We show γ-actinorhodin possesses many...
ABSTRACT Bacterial aminoacyl-tRNA synthetases (aaRSs) represent promising antibacterial drug targets. Unfortunately, the aaRS inhibitors that have to date reached clinical trials are subject rapid resistance development through mutation, a phenomenon limits their potential utility. Here, we confirm intuitively correct idea simultaneous targeting of two different enzymes prevents emergence spontaneous bacterial at high frequency, finding supports multitargeted anti-aaRS therapies.
N-Leucinyl benzenesulfonamides have been discovered as a novel class of potent inhibitors E. coli leucyl-tRNA synthetase. The binding to the enzyme was measured by using isothermal titration calorimetry. This provided information on enthalpy and entropy contributions binding, which, together with docking studies, were used for structure–activity relationship analysis. Enzymatic assays revealed that N-leucinyl display remarkable selectivity synthetase compared S. aureus human orthologues....
GSK2251052 is a broad-spectrum antibacterial inhibitor of leucyl tRNA-synthetase (LeuRS) that has been evaluated in phase II clinical trials. Here, we report the identification isolate Staphylococcus aureus exhibits reduced susceptibility to without prior exposure compound and demonstrate this phenotype attributable single amino acid polymorphism (P329) within editing domain LeuRS.
To address the growing antibiotic resistance problem, new antibacterial drugs must exert activity against pathogens resistant to agents already in use. With a view providing rapid means for deselecting drug candidates that fail meet this requirement, we report here generation and application of platform detecting cross-resistance between established novel agents.This first iteration (CRP) consists 28 strains defined genotype, uniform genetic background (the SH1000 strain clinically...
Whole-cell biosensor strains are powerful tools for antibacterial drug discovery, in principle allowing the identification of inhibitors acting on specific, high-value target pathways. Whilst a variety biosensors have been described detecting cell-wall biosynthesis (CWBIs), these typically lack specificity and/or sensitivity, and most part not rigorously evaluated as primary screening tools. Here, we describe several Staphylococcus aureus CWBI show that specific sensitive biosensor-based...