Summary
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.
Publications
Journals
Asai M, Li Y, Newton S, et al., 2023, Galleria mellonella-intracellular bacteria pathogen infection models: the ins and outs, Fems Microbiology Reviews, ISSN:0168-6445
Nahar N, Tram G, Jen FE-C, et al., 2023, Actinobacillus pleuropneumoniae encodes multiple phase-variable DNA methyltransferases that control distinct phasevarions, Nucleic Acids Research, ISSN:0305-1048
Li Y, Bosse J, Stringer O, et al., 2023, Detection of novel Actinobacillus pleuropneumoniae serovars by multiplex PCR: a cautionary tale, Microbiology Spectrum, ISSN:2165-0497, Pages:1-2
Li Y, Ma B, Hua K, et al., 2023, PPNet: Identifying functional association networks by phylogenetic profiling of prokaryotic genomes, Microbiology Spectrum, Vol:11, ISSN:2165-0497
Di Blasio S, Clarke M, Hind CK, et al., 2023, Bolaamphiphile analogues of 12-bis-THA Cl2 are potent antimicrobial therapeutics with distinct mechanisms of action against bacterial, mycobacterial, and fungal pathogens., Msphere, Vol:8, ISSN:2379-5042, Pages:1-20