A5020289426- Burkholderia infections and melioidosis
- Bacteriophages and microbial interactions
- Bacillus and Francisella bacterial research
- Antibiotic Resistance in Bacteria
- Chemical Looping and Thermochemical Processes
- Yersinia bacterium, plague, ectoparasites research
- Plant Virus Research Studies
- Moringa oleifera research and applications
- Brucella: diagnosis, epidemiology, treatment
- Evolution and Genetic Dynamics
- Bacterial Genetics and Biotechnology
- Religion, Society, and Development
- Insect symbiosis and bacterial influences
- Research on Leishmaniasis Studies
- Clostridium difficile and Clostridium perfringens research
- Vector-borne infectious diseases
- Cystic Fibrosis Research Advances
- Antimicrobial Peptides and Activities
- Galectins and Cancer Biology
- Microbial Inactivation Methods
- Mosquito-borne diseases and control
- Rabies epidemiology and control
- Food Security and Health in Diverse Populations
- Gut microbiota and health
- bioluminescence and chemiluminescence research
Defence Science and Technology Laboratory
2013-2025
University of Leicester
2022-2024
Aradigm (United States)
2017
The Burkholderia pseudomallei K96243 genome encodes six type VI secretion systems (T6SSs), but little is known about the role of these in biology B. pseudomallei. In this study, we purified recombinant Hcp proteins from each T6SS and tested them as vaccine candidates BALB/c mouse model melioidosis. Recombinant Hcp2 protected 80% mice against a lethal challenge with K96243, while Hcp1, Hcp3, Hcp6 50% challenge. was only constitutively produced by vitro; however, it not exported to...
The structure of BPSL1549, a protein unknown function from Burkholderia pseudomallei, reveals similarity to Escherichia coli cytotoxic necrotizing factor 1. We found that BPSL1549 acted as potent cytotoxin against eukaryotic cells and was lethal when administered mice. Expression levels bpsl1549 correlate with conditions expected promote or suppress pathogenicity. promotes deamidation glutamine-339 the translation initiation eIF4A, abolishing its helicase activity inhibiting translation. propose name
The interactions between bacteria and bacteriophage have important roles in the global ecosystem; turn changes environmental parameters affect phage. However, there is a lack of knowledge on whether clonal bacterial populations harbour different phenotypes that respond to phage distinct ways abundance such within affected by variations parameters. Here we study impact nutrient availability, growth rate T4 individual Escherichia coli cells confined spatial refuges. Surprisingly, found fast...
Bacteriophages represent an avenue to overcome the current antibiotic resistance crisis, but evolution of genetic phages remains a concern. In vitro, bacteria evolve resistance, preventing phage adsorption or degrading DNA. natural environments, evolved is lower possibly because spatial heterogeneity within biofilms, microcolonies, wall populations favours phenotypic survival lytic phages. However, it also possible that persistence genetically sensitive due less efficient amplification in...
The interactions between a virus and its host vary in space time are affected by the presence of molecules that alter physiology either or virus. Determining molecular mechanisms at basis these is paramount for predicting fate bacterial phage populations designing rational phage-antibiotic therapies. We study stationary phase Burkholderia thailandensis ΦBp-AMP1. Although heterogeneous genetic resistance to rapidly emerges B. , enhances efficacy three major antibiotic classes, quinolones,...
Burkholderia pseudomallei is the causative agent of melioidosis, a disease endemic to regions Southeast Asia and Northern Australia. Both humans range other animal species are susceptible production group 3 polysaccharide capsule in B. essential for virulence. capsular (CPS) I comprises unbranched manno -heptopyranose residues encoded by 34.5-kb locus on chromosome 1. Despite importance this locus, role all genes within region unclear. We inactivated 18 these analyzed their phenotype using...
<title>Abstract</title> The development of humane endpoints is critical for refining scientific studies involving animals. Body weight and clinical signs disease data collected in four recent assessing medical countermeasures utility against the melioidosis mice, was further analyzed. This work used this information to ascertain if a suitable alternative endpoint could be identified. A total 66 possible were explored, which varied threshold values ‘percentage body loss post-challenge’ ‘the...
Burkholderia pseudomallei is the causative agent of melioidosis, an infectious disease humans and animals. Gene clusters which encode capsular polysaccharide (type I O-PS) LPS II O-PS), both play roles in virulence, have previously been identified. Here, identification two further putative clusters, type III O-PS IV O-PS, reported. Mice challenged with or mutants showed increased mean times to death (7.8 11.6 days) compared those wild-type B. (3 days). To investigate possible polysaccharides...
ABSTRACT Macrophage infectivity potentiators (Mips) are a group of virulence factors encoded by pathogenic bacteria such as Legionella , Chlamydia and Neisseria species. Mips part the FK506-binding protein (FKBP) family, whose members typically exhibit peptidylprolyl cis-trans isomerase (PPIase) activity which is inhibitable immunosuppressants FK506 rapamycin. Here we describe identification characterization BPSS1823, Mip-like in intracellular pathogen Burkholderia pseudomallei . Recombinant...
ABSTRACT Liposome-encapsulated ciprofloxacin for inhalation (CFI) was investigated as a putative postexposure therapeutic two strains of Francisella tularensis . The efficacies oral and intranasally instilled CFI could not be distinguished in mouse model infection with the F. live vaccine strain (LVS), where single dose either formulation offered full protection against lethal challenge. However, studies more virulent Schu S4 demonstrated that higher level aerosol is provided by than...
ABSTRACT Burkholderia pseudomallei is the causative agent of melioidosis, a serious disease endemic in Southeast Asia and Northern Australia. Antibiotic treatment lengthy relapse often occurs. Finafloxacin novel fluoroquinolone with increased antibacterial activity acidic conditions contrast to other fluoroquinolones which demonstrate reduced at lower pH. Therefore, finafloxacin may have improved efficacy against B. , can survive within host cells where local pH acidic. In vitro analysis was...
Burkholderia pseudomallei, the causative agent of disease melioidosis, has been isolated from environment in 45 countries. The treatment melioidosis is complex, requiring lengthy antibiotic regimens, which can result relapse following cessation. It important that novel therapies to treat infections with B. pseudomallei be assessed appropriate animal models, and discussions regarding different protocols used between laboratories are critical. A 'deep dive' was held October 2020 focusing on...
Caenorhabditis elegans has previously been proposed as an alternative host for models of infectious disease caused by human pathogens. When exposed to some pathogenic bacteria, the life span nematodes is significantly reduced. We have shown that mutations in age-1, and/or age-2 genes C. elegans, normally enhance expectancy, can also increase resistance killing bacterial pathogens Pseudomonas aeruginosa, Salmonella enterica var. Typhimurium, Burkholderia cepacia or Yersinia...
ABSTRACT Many microbial pathogens express specific virulence traits at distinct growth phases. To understand the molecular pathways linking bacterial to pathogenicity, we have characterized transcriptome of Burkholderia pseudomallei , causative agent melioidosis. Using a fine-scale sampling approach, found approximately 17% all B. genes displaying regulated expression during in rich medium, occurring as broad waves functionally coherent gene tightly associated with phases and transition...
Inhalation of Yersinia pestis can lead to pneumonic plague, which without treatment is inevitably fatal. Two novel formulations liposome-encapsulated ciprofloxacin, 'ciprofloxacin for inhalation' (CFI, Lipoquin®) and 'dual release ciprofloxacin (DRCFI, Pulmaquin®) containing CFI solution, are in development. These were evaluated as potential therapies infection with Y. pestis. In a murine model human-like doses aerosolized CFI, DRCFI or intraperitoneal (i.p.) administered at 24 h...
Burkholderia pseudomallei is the causative agent of tropical disease melioidosis. Its genome encodes an arsenal virulence factors that allow it, when required, to switch from a soil dwelling bacterium deadly intracellular pathogen. With high intrinsic resistance antibiotics and ability overcome challenges host immune system, there increasing requirement for new greater understanding into molecular mechanisms B. dormancy. The peptidoglycan remodeling enzymes, lytic transglycosylases (Ltgs)...
Infection with aerosolized Francisella tularensis or Yersinia pestis can lead to lethal disease in humans if treatment is not initiated promptly. Finafloxacin a novel fluoroquinolone which has demonstrated broad-spectrum activity against range of bacterial species vitro, vivo , and humans, superior acidic, infection-relevant conditions.
Disulfiram (DSF) can help treat alcohol dependency by inhibiting aldehyde dehydrogenase (ALDH). Genomic analysis revealed that Francisella tularensis, the causative agent of tularemia, has lost all but one ALDH-like domain and this retains target DSF. In study, minimum inhibitory concentration (MIC) assays demonstrated both DSF its primary metabolite diethyldithiocarbamate (DDC) have strong antimicrobial activity against F. tularensis strain SCHU S4, with MIC determined as 2 µg/mL in...
This study investigated the in vitro activity of finafloxacin against panels biodefence pathogens. Broth microdilution assays were performed at neutral and acidic pH, to determine effectiveness antibiotics conditions typical an intracellular environment. In all instances, demonstrated superior low pH. These results highlight importance evaluating antimicrobial efficacy relevant those encountered vivo.
Melioidosis is a disease that difficult to treat due the causative organism,