A5074168173- Bacterial Genetics and Biotechnology
- Bacteriophages and microbial interactions
- Antibiotic Resistance in Bacteria
- Genomics and Phylogenetic Studies
- Crystallization and Solubility Studies
- Monoclonal and Polyclonal Antibodies Research
- X-ray Diffraction in Crystallography
- Gut microbiota and health
- Salmonella and Campylobacter epidemiology
- Escherichia coli research studies
- bioluminescence and chemiluminescence research
- Microbial Natural Products and Biosynthesis
- Trace Elements in Health
- Advanced Biosensing Techniques and Applications
- Antimicrobial Resistance in Staphylococcus
- Polar Research and Ecology
- Antimicrobial Peptides and Activities
- Click Chemistry and Applications
- Algal biology and biofuel production
- Immune Cell Function and Interaction
- Chemical Synthesis and Analysis
- Quinazolinone synthesis and applications
- Cell Image Analysis Techniques
- Biosimilars and Bioanalytical Methods
- Biosensors and Analytical Detection
University of Oxford
2023-2025
University of Sheffield
2021-2023
University of Bath
2016-2022
Ludwig-Maximilians-Universität München
2022
Florey Institute of Neuroscience and Mental Health
2021
More antibiotics are administered to livestock animals than treat human infections. Industrialization, large animal densities and early weaning mean pigs exposed more any other animal. Consequently, antimicrobial resistance (AMR) is common among commensal pathogenic bacteria. Heavy metals (HMs) also often used as feed additives for growth promotion infection prevention alongside antimicrobials, increased exposure copper, zinc cadmium can further encourage AMR through co-selection. In this...
Resistance against cell wall-active antimicrobial peptides in bacteria is often mediated by transporters. In low-GC-content Gram-positive bacteria, a common type of such transporters BceAB-like systems, which frequently provide high-level resistance peptide antibiotics that target intermediates the lipid II cycle wall synthesis. How transporter can offer protection from drugs are active on surface, however, has presented researchers with conundrum. Multiple theories have been discussed,...
Subtilin is a peptide antibiotic (lantibiotic) natively produced by Bacillus subtilis ATCC6633. It encoded in gene cluster spaBTCSIFEGRK (spa-locus) consisting of four transcriptional units: spaS (subtilin pre-peptide), spaBTC (modification and export), spaIFEG (immunity) spaRK (regulation). Despite the pioneer understanding on subtilin biosynthesis, robust platform to facilitate research improve production still poorly explored spot.In this work, intact spa-locus was successfully integrated...
Streptococcus pneumoniae is a major human pathogen and rising resistance to β-lactam antibiotics, such as penicillin, significant threat global public health. Mutations occurring in the penicillin-binding proteins (PBPs) can confer high-level penicillin but other poorly understood genetic factors are also important. Here, we combined strictly controlled laboratory experiments population analyses identify new pathway that independent of PBP modification. Initial selection identified...
ABSTRACT Recombination of short DNA fragments via horizontal gene transfer (HGT) can introduce beneficial alleles, create genomic disharmony through negative epistasis, and adaptive combinations positive epistasis. For non-core (accessory) genes, the epistatic cost is likely to be minimal because incoming genes have not co-evolved with recipient genome are frequently observed as tightly linked cassettes major effects. By contrast, interspecific recombination in core expected rare disruptive...
Antibiotic resistance poses a major threat to global health, and systematic studies understand the underlying mechanisms are urgently needed. Although significant progress has been made in deciphering mechanistic basis of individual determinants, many bacterial species rely on induction whole battery modules, complex regulatory networks controlling these modules response antibiotic stress often poorly understood. In this work we combined experiments theoretical modeling decipher network...
Significance Statement Genetic exchange among bacteria shapes the microbial world. From acquisition of antimicrobial resistance genes to fundamental questions about nature bacterial species, this powerful evolutionary force has preoccupied scientists for decades. However, mixing between species rests on a paradox. On one hand, promoting adaptation by conferring novel functionality, other potentially introducing disharmonious gene combinations (negative epistasis) that will be selected...
ABSTRACT Resistance against cell wall-active antimicrobial peptides in bacteria is often mediated by transporters. In low GC-content Gram-positive bacteria, a wide-spread type of such transporters are the BceAB-like systems, which frequently provide high level resistance peptide antibiotics that target intermediates lipid II cycle wall synthesis. How transporter can offer protection from drugs active on surface, however, has presented researchers with conundrum. Multiple theories have been...
Abstract Kinetic resolution provided a highly enantioselective method to access range of 3-aryl-3,4-dihydro-2H-1,4-benzoxazines using n-butyllithium and the chiral ligand sparteine. The enantioenrichment remained high on removing tert-butoxycarbonyl (Boc) protecting group. intermediate organolithium undergoes ring opening an enamine. kinetic was extended give enantiomerically enriched substituted 1,2,3,4-tetrahydroquinoxalines applied synthesis analogue antibiotic levofloxacin that screened...
Abstract Many archetypal and emerging classes of small-molecule therapeutics form covalent protein adducts. In vivo, both the resulting conjugates their off-target side-conjugates have potential to elicit antibodies, with implications for allergy drug sequestration. Although β-lactam antibiotics are a class long associated these immunological phenomena, molecular underpinnings drug-protein conjugation consequent drug-specific immune responses remain incomplete. Here, using classical...
Abstract Bacterial resistance against antibiotics often involves multiple mechanisms that are interconnected to ensure robust protection. So far, the knowledge about underlying regulatory features of those networks is sparse, since they can hardly be determined by experimentation alone. Here, we present first computational approach elucidate interplay between modules a single antibiotic, and how network structure allows cell respond compensate for perturbations resistance. Based on response...
Abstract Many classes of small-molecule drugs form protein adducts in vivo , which may elicit antibodies via a classical hapten-carrier-type response, with implications for both allergy and drug sequestration. Although β-lactam antibiotics are class long associated these phenomena, the molecular determinants drug-protein conjugation consequent drug-specific immune responses remain incomplete. Here, we interrogated factors influencing penicilloyl adduct formation immunogenicity, used...
Abstract BackgroundSubtilin is a peptide antibiotic (lantibiotic) natively produced by Bacillus subtilis ATCC6633. It encoded in gene cluster spaBTCSIFEGRK ( spa ‑locus) consisting of four transcriptional units: spaS (subtilin pre-peptide), spaBTC (modification and export), spaIFEG (immunity) spaRK (regulation). Despite the pioneer understanding on subtilin biosynthesis, robust platform to facilitate research improve production still poorly explored spot.ResultsIn this work, intact -locus...