- Antibiotic Resistance in Bacteria
- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- Bacterial biofilms and quorum sensing
- Helicobacter pylori-related gastroenterology studies
- Antibiotics Pharmacokinetics and Efficacy
- Antibiotic Use and Resistance
- Salmonella and Campylobacter epidemiology
- Antimicrobial Resistance in Staphylococcus
- Veterinary medicine and infectious diseases
- Vibrio bacteria research studies
- Cancer therapeutics and mechanisms
- Escherichia coli research studies
- Bacterial Identification and Susceptibility Testing
- Economic Theory and Policy
- Clostridium difficile and Clostridium perfringens research
- Antifungal resistance and susceptibility
- Reproductive tract infections research
- Microbial Metabolites in Food Biotechnology
- Global Financial Crisis and Policies
- Galectins and Cancer Biology
- Gastrointestinal disorders and treatments
- RNA and protein synthesis mechanisms
- Aquaculture disease management and microbiota
- Pharmaceutical and Antibiotic Environmental Impacts
World Health Organization
2024
Boston University
2020-2022
AstraZeneca (United States)
2000-2017
AstraZeneca (United Kingdom)
2011-2015
University of Cape Town
2015
Entasis Therapeutics (United States)
2015
Takeda (United States)
2015
AstraZeneca (Brazil)
1999-2014
The University of Queensland
1994-2004
Hôpital Pellegrin
2002
ABSTRACT Many clinical isolates of Pseudomonas aeruginosa cause infections that are difficult to eradicate due their resistance a wide variety antibiotics. Key genetic determinants were identified through genome sequences 390 P. , obtained from diverse geographic locations collected between 2003 and 2012 related microbiological susceptibility data for meropenem, levofloxacin, amikacin. β-Lactamases integron cassette arrangements enriched in the established multidrug-resistant lineages...
ABSTRACT Campylobacter jejuni strain 81-176 contains two, previously undescribed plasmids, each of which is approximately 35 kb in size. Although one the termed pTet, carries a tetO gene, conjugative transfer tetracycline resistance to another C. could not be demonstrated. Partial sequence analysis second plasmid, pVir, revealed presence four open reading frames encode proteins with significant similarity Helicobacter pylori proteins, including encoded by cag pathogenicity island. All these...
Summary Virulence of the opportunistic pathogen Pseudomonas aeruginosa involves coordinate expression a wide range virulence factors including type IV pili which are required for colonization host tissues and associated with form surface translocation termed twitching motility. Twitching motility in P. is controlled by complex signal transduction pathway shares many modules common chemosensory systems controlling flagella rotation bacteria composed, part, previously described proteins PilG,...
ABSTRACT The two complete genomic sequences of Helicobacter pylori J99 and 26695 were used to compare the paralogous families (related genes within one genome, likely have related function) predicted encode outer membrane proteins which present in each strain. We identified five gene ranging size from 3 33 members; these contained members specific for either H. or 26695. Most orthologous protein pairs (equivalent between genomes, same shared considerable identity strains. unusual set...
Campylobacter jejuni strain 81‐176 (HS36, 23) synthesizes two distinct glycan structures, as visualized by immunoblotting of proteinase K‐digested whole‐cell preparations. A site‐specific insertional mutant in the kpsM gene results loss expression a high‐molecular‐weight (HMW) (apparent M r 26 kDa to > 85 kDa) and increased resolution second ladder‐like 26–50 kDa). The is no longer typeable either HS23 or HS36 antisera, indicating that HMW structure serodeterminant HS36. Both ‐dependent...
Campylobacter coli VC167 T2 has two flagellin genes, flaA and flaB, which share 91.9% sequence identity. The gene is transcribed from a o-28 promoter, the flaB o-54 promoter. Gene replacement mutagenesis techniques were used to generate flaA+ flaB+ mutants. Both products are capable of assembling independently into functional filaments. A flagellar filament composed exclusively product indistinguishable in length that wild type shows slight reduction motility. severely truncated greatly...
Avibactam is a novel non-β-lactam β-lactamase inhibitor that inhibits wide range of β-lactamases. These include class A, C, and some D enzymes, which erode the activity β-lactam drugs in multidrug-resistant pathogens like Pseudomonas aeruginosa Enterobacteriaceae spp. currently clinical development combination with antibiotics ceftazidime, ceftaroline fosamil, aztreonam. has potential to be first might provide against C-mediated resistance, represents growing concern both hospital-...
Abstract Objectives The spread of NDM-1 amongst Enterobacteriaceae has highlighted a significant threat to the clinical management serious infections. combination aztreonam and avibactam, non-β-lactam β-lactamase inhibitor, may provide much-needed therapeutic alternative. This was potent against most NDM-containing Enterobacteriaceae, although activity diminished many Escherichia coli isolates. These E. isolates were characterized elucidate mechanism decreased susceptibility...
Abstract Objectives Pseudomonas aeruginosa is an important nosocomial pathogen that can cause a wide range of infections resulting in significant morbidity and mortality. Avibactam, novel non-β-lactam β-lactamase inhibitor, being developed combination with ceftazidime has the potential to be valuable addition treatment options for infectious diseases practitioner. We compared frequency resistance development ceftazidime/avibactam three P. strains carried derepressed ampC alleles. Methods The...
Ceftaroline, approved in Europe 2012, has activity against methicillin-resistant Staphylococcus aureus (MRSA), with MIC90 values of 1–2 mg/L depending on geographical location. During a global 2010 surveillance programme, conducted prior to the European launch, 4 S. isolates, out 8037 tested, possessing ceftaroline MIC >2 were identified. The objective this study was characterize these four isolates elucidate mechanism resistance. determinations performed using broth microdilution and whole...
Abstract With the diminishing effectiveness of current antibacterial therapies, it is critically important to discover agents that operate by a mechanism circumvents existing resistance. ETX0914, first new class agent targeted for treatment gonorrhea, operates novel mode-of-inhibition against bacterial type II topoisomerases. Incorporating an oxazolidinone on scaffold mitigated toxicological issues often seen with topoisomerase inhibitors. Organisms resistant other inhibitors were not...
ABSTRACT The circular pVir plasmid of Campylobacter jejuni strain 81-176 was determined to be 37,468 nucleotides in length with a G+C content 26%. A total 83% the represented coding information, and all but 2 54 predicted open reading frames were encoded on same DNA strand. There seven genes continguous region 8.9 kb that orthologs type IV secretion proteins found Helicobacter pylori, including four have been described previously (D. J. Bacon, R. A. Alm, D. H. Burr, L. Hu, Kopecko, C. P....
The opportunistic pathogen Pseudomonas aeruginosa produces type 4 fimbriae which promote adhesion to epithelial cells and are associated with a form of surface translocation called twitching motility. We have used transposon mutagenesis identify loci required for fimbrial assembly or function by screening mutants that lack the spreading colony morphology characteristic A subset these is resistant fimbria-specific phage. One (R270) was found contain insertion in new gene, termed pilZ, located...
Summary Type 4 fimbriae are important colonization factors in Pseudomonas aeruginosa and other pathogens that mediate attachment to epithelial cells of the host. They also responsible for a form translocation termed ‘twitching motility’ implicated susceptibility fimbrial‐specific bacteriophage. Analysis transposon mutant which lacks functional has identified new gene is required fimbrial biogenesis. This gene, pilV , located on chromosomal Spel fragment E, 2 kb downstream previously...
Mucoid strains of Pseudomonas aeruginosa isolated from the lungs cystic fibrosis patients produce large amounts exopolysaccharide alginate. AlgR has long been considered a key regulator alginate production, but its cognate sensor not identified. Here we show that is required for twitching motility, which form bacterial surface translocation mediated by type 4 fimbriae. Adjacent to algR have identified gene (fimS), also motility. However, FimS does appear be production in mucoid strains. and...
Novel non-fluoroquinolone inhibitors of bacterial type II topoisomerases (DNA gyrase and topoisomerase IV) are interest for the development new antibacterial agents that not impacted by target-mediated cross-resistance with fluoroquinolones. Aminopiperidines have a bicyclic aromatic moiety linked through carbon to an ethyl bridge, such as 1, generally show potent broad-spectrum activity, including quinolone-resistant isolates, but suffer from hERG inhibition (IC(50)= 3 μM 1). We now disclose...
The Class D (or OXA-type) β-lactamases have expanded to be the most diverse group of serine with a highly heterogeneous β-lactam hydrolysis profile and are typically resistant marketed β-lactamase inhibitors. enzymes increasingly found in multidrug (MDR) Acinetobacter baumannii, Pseudomonas aeruginosa, various species Enterobacteriaceae posing serious threat clinical utility β-lactams including carbapenems, which reserved as drugs last resort. Avibactam, novel non-β-lactam inhibitor, not...