The research in my group focuses on respiratory and/or meningitis-causing pathogens of man, e.g. Neisseria meningitidis, Haemophilus influenzae and Mycobacterium tuberculosis, and animals e.g. Actinobacillus pleuropneumoniae (APP), Haemophilus parasuis, Pasteurella multocida. Dependent on the pathogen, the aims are to improve vaccines, diagnostics, therapeutics and a greater understanding of the basis of bacterial pathogenicity. A major focus of our work is on the pig pathogen APP carried out in collaboration with Professor Andrew Rycroft (Royal Veterinary College London). We have developed high throughput genome wide mutagenesis protocols and screens (based on Transposon Directed Insertion site Sequencing [TraDIS]) to identify APP genes essential for growth in vitro and in vivo, with a view to developing novel antimicrobial and vaccine strategies. The methods developed are applicable to other pathogenic members of the Pasteurellaceae i.e. Aggregatibacter actinomycetemcomitans, H. influenzae, Mannheimia haemolytica, and P. multocida.
In collaboration with Dr Anastasia Callaghan (University of Portsmouth) and Professor Denise Bazzolli (University of Viçosa, Brazil) we are evaluating whether inhibition of sRNAs of APP is a viable control strategy. Other collaborations include that with the UK Animal and Plant Health Agency (APHA) and the Wellcome Trust Sanger Centre, where we have identified in APP (1) plasmid borne dfr14 genes (mediating resistance to trimethoprim), the first description in any member of the Pasteurellaceae; and (2) sequenced plasmids mediating florfenicol resistance and ampicillin. Additionally, in a collaboration involving Drs Ee (National University of Singapore) and Yang (Institute of Bioengineering and Nanotechnology, Singapore), and Drs Sandra Newton and Brian Robertson (Imperial College London), rationally designed antimicrobial peptides are being tested for their efficacy in vitro and in vivo to inhibit M. tuberculosis.
In addition, we are seeking vaccine candidates that will prevent disease caused by Neisseria meningitidis serogroup B infections. Monoclonal antibodies are derived from patients recovering from meningococcal disease, and the proteins recognised on the surface of the bacterium determined.
et al., Structural, Functional, and Immunogenic Insights on Cu,ZnSuperoxide Dismutase Pathogenic Virulence Factors from Neisseriameningitidis and Brucella abortus., Journal of Bacteriology, ISSN:1098-5530
et al., 2018, Proposal of serovars 17 and 18 of Actinobacillus pleuropneumoniae based on serological and genotypic analysis, Veterinary Microbiology, Vol:217, ISSN:0378-1135, Pages:1-6
et al., 2018, Use of Proteins Identified through a Functional Genomic Screen To Develop a Protein Subunit Vaccine That Provides Significant Protection against Virulent Streptococcus suis in Pigs, Infection and Immunity, Vol:86, ISSN:0019-9567
et al., 2018, Characterization of the Actinobacillus pleuropneumoniae SXT-related integrative and conjugative element ICEApl2 and analysis of the encoded FloR protein: hydrophobic residues in transmembrane domains contribute dynamically to florfenicol and chloramphenicol efflux, Journal of Antimicrobial Chemotherapy, Vol:73, ISSN:0305-7453, Pages:57-65
, Bacterial virulence genes