A5076780533- Antibiotic Resistance in Bacteria
- Genomics and Phylogenetic Studies
- Bacterial biofilms and quorum sensing
- Vibrio bacteria research studies
- Bacterial Identification and Susceptibility Testing
- Bacteriophages and microbial interactions
- Plant Pathogenic Bacteria Studies
- Bacterial Genetics and Biotechnology
- Single-cell and spatial transcriptomics
- Invertebrate Immune Response Mechanisms
- Insect symbiosis and bacterial influences
- Gut microbiota and health
- Evolution and Genetic Dynamics
- Antibiotics Pharmacokinetics and Efficacy
- Microbial infections and disease research
- Genetic diversity and population structure
- Species Distribution and Climate Change
- Antimicrobial Peptides and Activities
- RNA and protein synthesis mechanisms
- Plant Virus Research Studies
- Animal Disease Management and Epidemiology
- Clostridium difficile and Clostridium perfringens research
- Zoonotic diseases and public health
- Streptococcal Infections and Treatments
- Amphibian and Reptile Biology
University of Cambridge
2020-2023
Wellcome Sanger Institute
2018-2021
Helmholtz Centre for Infection Research
2012-2020
Center for Experimental and Clinical Infection Research
2015-2018
Medizinische Hochschule Hannover
2012-2015
Technische Universität Braunschweig
2013
We compared the dynamics and mechanisms of resistance development to ceftazidime, meropenem, ciprofloxacin, ceftolozane-tazobactam in wild-type (PAO1) mutator (PAOMS, ΔmutS) P. aeruginosa. The strains were incubated for 24 h with 0.5 64× MICs each antibiotic triplicate experiments. tubes from highest concentration showing growth reinoculated fresh medium containing concentrations up MIC 7 consecutive days. susceptibility profiles assessed two isolated colonies step, antibiotic, strain....
Sigma factors are essential global regulators of transcription initiation in bacteria which confer promoter recognition specificity to the RNA polymerase core enzyme. They provide effective mechanisms for simultaneously regulating expression large numbers genes response challenging conditions, and their presence has been linked bacterial virulence pathogenicity. In this study, we constructed nine his-tagged sigma factor expressing and/or deletion mutant strains opportunistic pathogen...
ABSTRACT Quinolone antibiotics constitute a clinically successful and widely used class of broad-spectrum antibiotics; however, the emergence spread resistance increasingly limits use fluoroquinolones in treatment management microbial disease. In this study, we evaluated quantitative contributions quinolone target alteration efflux pump expression to fluoroquinolone Pseudomonas aeruginosa . We generated isogenic mutations hot spots resistance-determining regions (QRDRs) gyrA , gyrB parC...
Antimicrobial resistance (AMR) poses a threat to public health. Clinical microbiology laboratories typically rely on culturing bacteria for antimicrobial-susceptibility testing (AST). As the implementation costs and technical barriers fall, whole-genome sequencing (WGS) has emerged as ‘one-stop’ test epidemiological predictive AST results. Few published comparisons exist myriad analytical pipelines used predicting AMR. To address this, we performed an inter-laboratory study providing sets of...
The expansion and intensification of livestock production is predicted to promote the emergence pathogens. As pathogens sometimes jump between species, this can affect health humans as well livestock. Here, we investigate how microbiota act a source these emerging through analysis Streptococcus suis , ubiquitous component respiratory pigs that also major cause disease on pig farms an important zoonotic pathogen. Combining molecular dating, phylogeography, comparative genomic analyses large...
Emerging resistance to antimicrobials and the lack of new antibiotic drug candidates underscore need for optimization current diagnostics therapies diminish evolution spread multidrug resistance. As status a bacterial pathogen is defined by its genome, profiling applying next-generation sequencing (NGS) technologies may in future accomplish identification, prompt initiation targeted individualized treatment, implementation optimized infection control measures. In this study, qualitative RNA...
Infections caused by Klebsiella pneumoniae are a major public health threat. Extensively drug-resistant and even pan-resistant strains have been reported. Understanding K. pathogenesis is hampered the fact that murine models of infection offer limited resolution for non-hypervirulent which cause majority infections. The insect Galleria mellonella larva widely used alternative model organism bacterial pathogens. We performed genome-scale fitness profiling multidrug-resistant ST258 strain...
Extensive use of next-generation sequencing (NGS) for pathogen profiling has the potential to transform our understanding how genomic plasticity contributes phenotypic versatility. However, storage large amounts NGS data and visualization tools need evolve offer scientific community fast convenient access these data. We introduce BACTOME as a database system that links aligned DNA- RNA-sequencing reads clinical Pseudomonas aeruginosa isolates with clinically relevant phenotypes. The allows...
Genome-wide association studies (GWAS) are increasingly being applied to investigate the genetic basis of bacterial traits. However, approaches perform power calculations for GWAS limited. Here we implemented two alternative conduct using existing collections genomes. First, a sub-sampling approach was undertaken reduce allele frequency and effect size known detectable genotype-phenotype relationship by modifying phenotype labels. Second, phenotype-simulation conducted simulate phenotypes...
Health-care-associated infections by multi-drug-resistant bacteria constitute one of the greatest challenges to modern medicine. Bacterial pathogens devise various mechanisms withstand activity a wide range antimicrobial compounds, among which acquisition carbapenemases is most concerning. In Klebsiella pneumoniae, dissemination K. pneumoniae carbapenemase tightly connected global spread certain clonal lineages. Although antibiotic resistance key driver for distribution epidemic high-risk...
Summary Pseudomonas aeruginosa is an environmental microorganism and a causative agent of diverse acute chronic, biofilm‐associated infections. Advancing research‐based knowledge on its adaptation to conditions within the human host bound reveal novel strategies targets for therapeutic intervention. Here, we investigated traits that P. PA14 as well virulence attenuated Δ lasR mutant need survive in selected murine infection models. Experimentally, genetic programs bacteria use adapt versus...
Abstract Background Antimicrobial resistance (AMR) poses a threat to public health. Clinical microbiology laboratories typically rely on culturing bacteria for antimicrobial susceptibility testing (AST). As the implementation costs and technical barriers fall, whole-genome sequencing (WGS) has emerged as ‘one-stop’ test epidemiological predictive AST results. Few published comparisons exist myriad analytical pipelines used predicting AMR. To address this, we performed an inter-laboratory...
Summary The c‐di‐GMP‐binding effector protein FlgZ has been demonstrated to control motility in the opportunistic pathogen Pseudomonas aeruginosa and it was suggested that c‐di‐GMP‐bound impedes via its interaction with MotCD stator. To further understand how is downregulated P. elucidate general mechanisms operating during bacterial growth, we examined spatiotemporal activity of FlgZ. We re‐annotated aeruginosaflgZ open reading frame FlgZ‐mediated downregulation fine‐tuned three independent...
Mutation rates vary both within and between bacterial species, understanding what drives this variation is essential for the evolutionary dynamics of populations. In study, we investigate two factors that are predicted to influence mutation rate: ecology genome size. We conducted accumulation experiments on eight strains emerging zoonotic pathogen Streptococcus suis . Natural species allows us compare tonsil carriage invasive disease isolates, from more less pathogenic populations, with a...
ABSTRACT The long-known resistance to pathogens provided by host-associated microbiota fostered the notion that adding protective bacteria could prevent or attenuate infection. However, identification of endogenous exogenous conferring such protection is often hindered complexity host microbial communities. Here, we used zebrafish and fish pathogen Flavobacterium columnare as a model system study determinants microbiota-associated colonization resistance. We compared infection susceptibility...
Abstract While mutation is often deleterious, it can also be adaptive. Mutation rates vary both within and between bacterial species, understanding what drives this variation essential for the evolutionary dynamics of populations. In study we investigate two factors that are predicted to influence trade-off costs benefits mutation: ecology genome size. To relationship these rate conducted accumulation experiments on eight strains emerging zoonotic pathogen Streptococcus suis . Natural...
Abstract Infections caused by Klebsiella pneumoniae are a major public health threat. Extensively drug-resistant and even pan-resistant strains have been reported. Understanding K. pathogenesis is hampered the fact that murine models of infection offer limited resolution for non-hypervirulent which cause majority infections. We performed genome-scale fitness profiling multidrug-resistant ST258 strain during insect Galleria mellonella, with aim to determine if this model suitable large-scale...