A5084292546- Salmonella and Campylobacter epidemiology
- Bacteriophages and microbial interactions
- Vibrio bacteria research studies
- Bacterial Genetics and Biotechnology
- Viral gastroenteritis research and epidemiology
- Escherichia coli research studies
- Genomics and Phylogenetic Studies
- RNA and protein synthesis mechanisms
- Photosynthetic Processes and Mechanisms
- Antibiotic Resistance in Bacteria
- Trace Elements in Health
- Legume Nitrogen Fixing Symbiosis
- Bacterial biofilms and quorum sensing
- Aquaculture disease management and microbiota
- IL-33, ST2, and ILC Pathways
- Microbial Fuel Cells and Bioremediation
- Microbial Metabolic Engineering and Bioproduction
- Plant biochemistry and biosynthesis
- Vitamin C and Antioxidants Research
- Eosinophilic Esophagitis
- Cancer Research and Treatments
- Blood groups and transfusion
- Gut microbiota and health
- Animal Nutrition and Physiology
- Porphyrin Metabolism and Disorders
University of Basel
2021-2025
University of Liverpool
2017-2024
Genomics (United Kingdom)
2019
University of Lausanne
2010-2014
Abstract Bloodstream infections caused by nontyphoidal Salmonella are a major public health concern in Africa, causing ~49,600 deaths every year. The most common enterica pathovariant associated with invasive disease is Typhimurium sequence type (ST)313. It has been proposed that antimicrobial resistance and genome degradation contributed to the success of ST313 lineages but evolutionary trajectory such changes was unclear. Here, define dynamics ST313, we sub-sampled from two comprehensive...
Significance Invasive nontyphoidal Salmonella disease is a major and previously neglected tropical responsible for an estimated ∼390,000 deaths per year in Africa, largely caused by variant of Typhimurium called ST313. Despite the availability >100,000 genomes, it has proven challenging to associate individual SNPs with pathogenic traits this dangerous bacterium. Here, we used transcriptomic strategy identify single-nucleotide change promoter region crucial phenotypic differences African...
Abstract Some enteric bacteria including Salmonella have evolved the propanediol-utilising microcompartment (Pdu MCP), a specialised proteinaceous organelle that is essential for 1,2-propanediol degradation and pathogenesis. Pdu MCPs are family of bacterial microcompartments self-assembled from hundreds proteins within cytosol. Here, we seek comprehensive understanding stoichiometric composition organisation MCPs. We obtain accurate stoichiometry shell internal enzymes natural MCP by...
In the past 30 years, Salmonella bloodstream infections have become a significant health problem in sub-Saharan Africa and are responsible for deaths of an estimated 390,000 people each year. The disease is predominantly caused by recently described sequence type Typhimurium: ST313, which has distinctive set prophage sequences. We thoroughly characterized ST313-associated prophages both genetically experimentally. ST313 representative strain D23580 contains 5 full-length prophages: BTP1,...
Salmonella Typhimurium sequence type (ST) 313 causes invasive nontyphoidal (iNTS) disease in sub-Saharan Africa, targeting susceptible HIV+, malarial, or malnourished individuals. An in-depth genomic comparison between the ST313 isolate D23580 and well-characterized ST19 4/74 that gastroenteritis across globe revealed extensive synteny. To understand how 856 nucleotide variations generated phenotypic differences, we devised a large-scale experimental approach involved global gene expression...
The opportunistic human pathogen Pseudomonas aeruginosa is able to utilize a wide range of carbon and nitrogen compounds, allowing it grow in vastly different environments. uptake catabolism growth substrates are organized hierarchically by mechanism termed catabolite repression control (Crc) whereby the Crc protein establishes translational target mRNAs at CA (catabolite activity) motifs present near ribosome binding sites. Poor sources lead activation CbrAB two-component system, which...
Summary The opportunistic pathogen P seudomonas aeruginosa PAO1 has a remarkable capacity to adapt various environments and survive with limited nutrients. Here, we report the discovery characterization of novel small non‐coding RNA : NrsZ (nitrogen‐regulated sRNA ). We show that under nitrogen limitation, is induced by NtrB / C two‐component system, an important regulator assimilation . aeruginosa's swarming motility, in concert alternative sigma factor RpoN Furthermore, demonstrate...
Abstract Bacterial metabolosomes are a family of protein organelles in bacteria. Elucidating how thousands proteins self-assemble to form functional is essential for understanding their significance cellular metabolism and pathogenesis. Here we investigate the de novo biogenesis propanediol-utilization (Pdu) characterize roles key constituents generation intracellular positioning metabolosomes. Our results demonstrate that Pdu metabolosome undertakes both “Shell first” “Cargo assembly...
Prophages are integrated phage elements that a pervasive feature of bacterial genomes. The fitness bacteria is enhanced by prophages confer beneficial functions such as virulence, stress tolerance or resistance, and these encoded 'accessory' 'moron' loci. Whilst the majority phage-encoded genes repressed during lysogeny, accessory loci often highly expressed. However, it challenging to identify novel prophage from DNA sequence data alone. Here, we use RNA-seq examine transcriptional...
Abstract Bacterial capsules are major virulence factors enabling systemic infection by undermining innate and adaptive immunity. Capsular polysaccharides also the antigen in some of most successful antibacterial vaccines – including pneumococcal, neisserial Hib conjugate vaccines. However, it remains exceptionally challenging to study capsules, primarily due their high chemical diversity limited methods available for detection analysis. We describe a robust biochemical method analysis ABC...
Colonization of the intestinal lumen precedes invasive infection for a wide range enteropathogenic and opportunistic pathogenic bacteria. We show that combining oral vaccination with engineered or selected niche-competitor strains permits pathogen exclusion strain replacement in mouse gut lumen. This approach can be applied either prophylactically to prevent invasion nontyphoidal Salmonella strains, therapeutically displace an established Escherichia coli. Both intact adaptive immunity...
Background Reptile-associated Salmonella bacteria are a major, but often neglected cause of both gastrointestinal and bloodstream infection in humans globally. The diversity enterica has not yet been determined venomous snakes, however other ectothermic animals have reported to carry broad range bacteria. We investigated the prevalence collection snakes non-venomous reptiles. Methodology/Principle findings used combination selective enrichment techniques establish unique dataset reptilian...
Bacteriophages (phages) outnumber bacteria ten-to-one and cause infections at a rate of 10
Abstract Invasive non-typhoidal Salmonella (iNTS) disease is a serious bloodstream infection that targets immune-compromised individuals, and causes significant mortality in sub-Saharan Africa. enterica serovar Typhimurium ST313 the majority of iNTS Malawi. We performed an intensive comparative genomic analysis 608 S. isolates dating between 1996 2018 from Blantyre, discovered following arrival well-characterized lineage 2 1999, two multidrug-resistant variants emerged Malawi 2006 2008,...
Over recent decades, Salmonella infection research has predominantly relied on murine models. However, in many cases the phenotypes of pathovars mice do not recapitulate human disease. For example, Typhimurium ST313 is associated with enhanced invasive immunocompromised people Africa, but and other animal models have consistently reproduced this phenotype. The introduction alternative could help to improve quality reproducibility pathogenesis by facilitating larger-scale experiments. To...
The various sub-species of Salmonella enterica cause a range disease in human hosts. human-adapted serovar Typhi enters the gastrointestinal tract and invades systemic sites to enteric (typhoid) fever. In contrast, most non-typhoidal serovars are primarily restricted gut tissues. Across Africa, invasive (iNTS) have emerged with an ability spread beyond bloodstream infections increased morbidity mortality. To investigate this evolution pathogenesis, we compared genomes African iNTS isolates...
Salmonella enterica Enteritidis is the second most common serovar associated with invasive non-typhoidal (iNTS) disease in sub-Saharan Africa. Previously, genomic and phylogenetic characterization of S . isolates from human bloodstream led to discovery Central/Eastern African clade (CEAC) West clade, which were distinct gastroenteritis-associated global epidemic (GEC). The clades have unique genetic signatures that include degradation, novel prophage repertoires multi-drug resistance, but...
In recent years, novel lineages of invasive non-typhoidal Salmonella (iNTS) serovars Typhimurium and Enteritidis have been identified in patients with bloodstream infection Sub-Saharan Africa. Here, we isolated characterised 32 phages capable infecting S. Enteritidis, from water sources Malawi the UK. The were classified three major phylogenetic clusters that geographically distributed. terms host range, Cluster 1 able to infect all bacterial hosts tested, whereas Clusters 2 3 had a more...
The FinO-domain protein ProQ belongs to a widespread family of RNA-binding proteins (RBPs) involved in gene regulation bacterial chromosomes and mobile elements. While the cellular RNA targets have been established diverse bacteria, functionally crucial residues remain be identified under physiological conditions. Following our discovery that deficiency alleviates growth suppression Salmonella with succinate as sole carbon source, an experimental evolution approach was devised exploit this...
Summary Temperate phages are pervasive in bacterial genomes, existing as vertically-inherited islands called prophages. Prophages vulnerable to the predation of their host bacterium by exogenous phages. Here we identify BstA, a novel family prophage-encoded phage defense proteins found diverse Gram-negative bacteria. BstA drives potent suppression epidemics through abortive infection. During lytic replication, bstA -encoding prophage is not itself inhibited due self-immunity mechanism...
ABSTRACT Integrated phage elements, known as prophages, are a pervasive feature of bacterial genomes. Prophages can enhance the fitness their hosts by conferring beneficial functions, such virulence, stress tolerance or resistance, which encoded accessory loci. Whilst majority phage-encoded genes repressed during lysogeny, loci often highly expressed. However, novel prophage challenging to identify based on DNA sequence data alone. Here, we use RNA-seq examine transcriptional landscapes five...
Colonization of the intestinal lumen precedes invasive infection for a wide range enteropathogenic and opportunistic pathogenic bacteria. Here we show that combining oral vaccination with engineered or selected niche-competitor strains permits pathogen exclusion strain replacement in mouse gut lumen. This approach can be applied both prophylactically to prevent invasion non-typhoidal Salmonella strains, therapeutically displace an established Escherichia coli. Both intact adaptive immunity...
Bacteria have evolved a broad range of systems that provide defence against their viral predators, bacteriophages. Bacteriophage Exclusion (BREX) recognize and methylate 6 bp non-palindromic motifs within the host genome, prevent replication non-methylated phage DNA encodes these same motifs. How BREX recognizes cognate has not been fully understood. We characterised from pathogenic Salmonella generated first X-ray crystallographic structures conserved protein, PglX. The PglX N-terminal...