A5036631894- Antibiotic Resistance in Bacteria
- Antibiotics Pharmacokinetics and Efficacy
- Fungal and yeast genetics research
- Urinary Tract Infections Management
- Fungal Biology and Applications
- Antifungal resistance and susceptibility
- Cellular Mechanics and Interactions
- Microbial Natural Products and Biosynthesis
- Fungal Infections and Studies
- Plant Reproductive Biology
- Pneumonia and Respiratory Infections
- Mycorrhizal Fungi and Plant Interactions
- Antibiotic Use and Resistance
- Muscle metabolism and nutrition
- Plant-Microbe Interactions and Immunity
- Probiotics and Fermented Foods
- Nail Diseases and Treatments
- Nephrotoxicity and Medicinal Plants
- Plant Gene Expression Analysis
- Plant Pathogens and Fungal Diseases
- Cardiovascular and exercise physiology
- Pharmaceutical and Antibiotic Environmental Impacts
- Plant biochemistry and biosynthesis
- High Altitude and Hypoxia
Evolva (Switzerland)
2009-2013
Institut National de la Recherche Agronomique
2008
University of Basel
2000-2008
Institut Pasteur
2005
Importance Cefepime/enmetazobactam is a novel β-lactam/β-lactamase inhibitor combination and potential empirical therapy for resistant gram-negative infections. Objective To evaluate whether cefepime/enmetazobactam was noninferior to piperacillin/tazobactam the primary outcome of treatment efficacy in patients with complicated urinary tract infections (UTIs) or acute pyelonephritis. Design, Setting, Participants A phase 3, randomized, double-blind, active-controlled, multicenter,...
Enmetazobactam, formerly AAI101, is a novel penicillanic acid sulfone extended-spectrum β-lactamase (ESBL) inhibitor. The combination of enmetazobactam with cefepime has entered clinical trials to assess safety and efficacy in patients complicated urinary tract infections. Here, the vitro activity cefepime-enmetazobactam was determined for 1,993 isolates Enterobacteriaceae Pseudomonas aeruginosa collected United States Europe during 2014 2015. Enmetazobactam at fixed concentration 8 μg/ml...
Natural products are an important source of drugs and other commercially interesting compounds, however their isolation production is often difficult. Metabolic engineering, mainly in bacteria yeast, has sought to circumvent some the associated problems but also this approach impeded by technical limitations. Here we describe a novel strategy for diverse natural products, comprising expression unprecedented large number biosynthetic genes heterologous host.As example, from different sources,...
We used actin staining and videomicroscopy to analyze the development from a spore young mycelium in filamentous ascomycete Ashbya gossypii. The starts with an initial isotropic growth phase followed by emergence of germ tubes. tip speed 6-10 microm/h increases during early stages development. This increase is transiently interrupted response establishment lateral branches or septa. hyphal finally reaches maximum up 200 micro/h, tips these mature hyphae have ability split into two equally...
Characteristic features of morphogenesis in filamentous fungi are sustained polar growth at tips hyphae and frequent initiation novel sites (branches) along the extending hyphae. We have begun to study regulation this process on molecular level by using model fungus Ashbya gossypii. found that A. gossypii Ras-like GTPase Rsr1p/Bud1p localizes tip region it is involved apical polarization actin cytoskeleton, a determinant direction. In absence RSR1/BUD1, hyphal was severely slowed down due...
This study aimed to investigate third-generation cephalosporin (3GC) resistance determinants [extended-spectrum β-lactamases (ESBLs), AmpC and OXA-type β-lactamases] in contemporary clinical Enterobacterales isolates determine the vitro activity of β-lactams β-lactam/β-lactamase inhibitor combinations, including investigational combination cefepime novel β-lactamase enmetazobactam. Antibacterial susceptibility 7168 obtained between 2016–2018 from North America Europe was determined according...
ABSTRACT Filamentous fungi grow by hyphal extension, which is an extreme example of polarized growth. In contrast to yeast species, where growth the tip emerging bud temporally limited, filamentous exhibit constitutive tip. many fungi, including Ashbya gossypii, reinforced a process called maturation. Hyphal maturation refers developmental switch from slow-growing hyphae young mycelium fast-growing mature mycelium. This essential for efficient expansion We report first time on identification...
Members of the dual-specificity tyrosine-phosphorylated and regulated kinase (DYRK) family perform a variety functions in eukaryotes. We used gene disruption, targeted pharmacologic inhibition, genome-wide transcriptional profiling to dissect function Yak1 DYRK human fungal pathogen Candida albicans. C. albicans strains with mutant yak1 alleles showed defects yeast-to-hypha transition maintaining hyphal growth. They also could not form biofilms. Despite their vitro filamentation defect,...
Klebsiella pneumoniae strains that produce extended-spectrum beta lactamases (ESBLs) are a persistent public health threat. There relatively few therapeutic options, and there is undue reliance on carbapenems. Alternative options urgently required. A combination of cefepime the novel lactamase inhibitor enmetazobactam being developed for treatment serious infections caused by ESBL-producing organisms. The pharmacokinetics-pharmacodynamics (PK-PD) cefepime-enmetazobactam against K. was...
Third-generation cephalosporin (3GC)-resistant Enterobacteriaceae are classified as critical priority pathogens, with extended-spectrum β-lactamases (ESBLs) principal resistance determinants. Enmetazobactam (formerly AAI101) is a novel ESBL inhibitor developed in combination cefepime for empirical treatment of serious Gram-negative infections settings where ESBLs prevalent. Cefepime-enmetazobactam has been investigated phase 3 trial patients complicated urinary tract or acute pyelonephritis.
Cefepime-enmetazobactam is a novel β-lactam–β-lactamase inhibitor combination with broad-spectrum antimicrobial activity against range of multidrug-resistant Enterobacteriaceae . This agent being developed for serious hospital infections. An understanding the extent partitioning combinations into human lung required to better understand potential role cefepime-enmetazobactam treatment nosocomial pneumonia.
ABSTRACT Unlike most other cells, hyphae of filamentous fungi permanently elongate and lack nonpolar growth phases. We identified AgBoi1/2p in the ascomycete Ashbya gossypii as a component required to prevent at hyphal tips. Strains lacking frequently show spherical enlargement tips with concomitant depolarization actin patches loss tip-located cables. These enlarged can repolarize resume tip extension previous polarity axis. localizes transiently sites septation. Only localization is...
Human fungal infections represent a therapeutic challenge. Although effective strategies for treatment are available, resistance is spreading, and many therapies have unacceptable side effects. A clear need novel antifungal targets molecules thus emerging. Here, we present the identification characterization of plant-derived diyne-furan fatty acid EV-086 as compound. has potent broad-spectrum activity in vitro against Candida, Aspergillus, Trichophyton spp., whereas activities bacteria human...
Third-generation cephalosporin resistance among Enterobacteriaceae, mediated by the spread of extended-spectrum β-lactamases (ESBLs), is a very serious medical concern with limited therapeutic options. Enmetazobactam (formerly AAI101) novel penicillanic sulfone β-lactamase inhibitor active against wide range ESBLs. The combination enmetazobactam and cefepime has entered phase 3 development in patients complicated urinary tract infections. Using Clinical Laboratory Standards Institute (CLSI)...
The use of carbapenem antibiotics to treat infections caused by Enterobacterales expressing increasingly aggressive extended-spectrum β-lactamases (ESBLs) has contributed the emergence resistance. Enmetazobactam is a novel ESBL inhibitor being developed in combination with cefepime as carbapenem-sparing option for ESBL-producing Enterobacterales. Cefepime-enmetazobactam checkerboard MIC profiles were obtained challenge panel cefepime-resistant clinical isolates Klebsiella pneumoniae. Sigmoid...
Abstract Background Third-generation cephalosporin (3GC)-resistant Enterobacteriaceae has been classified as critical priority pathogens. The novel extended-spectrum β-lactamase (ESBL) inhibitor enmetazobactam (formerly AAI101; EMT) in combination with cefepime (FEP) is currently being developed a carbapenem-sparing treatment of serious Gram-negative infections settings high prevalence 3GC-resistant Enterobacteriaceae. We report here the results from phase 2 study that assessed safety,...
Abstract Background There is a critical need for carbapenem-sparing therapies infections caused by extended spectrum β-lactamase (ESBL)-producing Enterobacterales. Enmetazobactam novel ESBL inhibitor combined with the cephalosporin cefepime. Treatment outcomes of cefepime-enmetazobactam (FPE) versus piperacillin-tazobactam (PTZ) were assessed in subgroups patients ESBL-producing baseline uropathogens (ESBL-BU) ALLIUM phase 3 trial complicated urinary tract (cUTI)/acute pyelonephritis (AP)....