My research is focused on understanding pathogenic mechanisms of Actinobacillus pleuropneumoniae (APP), a strict bacterial parasite of the porcine respiratory tract. It is the etiologic agent of porcine pleuropneumonia, a highly contagious infection responsible for substantial economic losses to the worldwide pig production industry. As a member of the Pasteurellaceae family, which also includes the human pathogen Haemophilus influenzae, APP provides the opportunity to study actual host/pathogen interactions, rather than relying on use of animal models.
Since completing my PhD at the University of Guelph, Canada, I have worked with Professor Paul Langford in the Molecular Infectious Disease Group, Division of Paediatrics, Imperial College London. Together, we have published over 50 papers and have developed strong collaborations with other academic groups in the UK, as well as with groups in Canada, Germany, Denmark, Hungary, Brazil and China. Currently, I am co-investigator on a BBSRC-funded project entitled ‘sRNA-based therapeutics for disease caused by A. pleuropneumoniae’, and recently completed a six-month Fellowship in Brazil related to this work.
Having developed a number of genetic tools to allow functional genomic analysis of APP and other related bacteria, we are focusing on identifying key virulence factors and pathways that can be exploited for development of novel therapeutic and vaccine strategies. To underpin these studies, we have amassed a database of whole genome sequences (wgs) of clinical isolates of APP and related swine respiratory bacteria. Analysis of these wgs has provided insights into mechanisms of antimicrobial resistance, and has allowed us to develop comprehensive molecular diagnostics for capsule typing of APP.
We are also building a database of predicted sRNAs, identified from RNASeq data of APP grown under a variety of conditions, and in collaboration with groups led by Professor Anastasia Callaghan (University of Portsmouth) and Dr Denise Bazzolli (University of Viçosa, Brazil), we have begun to evaluate individual sRNAs for their contribution to certain phenotypes in vitro, as well as to virulence in a Galleria mellonella wax moth worm model of infection. In addition to identifying possible targets for therapeutics, these data greatly expand our understanding of the basic regulatory mechanisms employed by this important pathogen.
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., 2017, Characterisation 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
et al., 2017, Whole genome sequencing for surveillance of antimicrobial resistance in Actinobacillus pleuropneumoniae, Frontiers in Microbiology, Vol:8, ISSN:1664-302X
et al., 2017, The N-linking glycosylation system from Actinobacillus pleuropneumoniae is required for adhesion and has potential use in glycoengineering, Open Biology, Vol:7, ISSN:2046-2441
et al., 2016, A computational strategy for the search of regulatory small RNAs inActinobacillus pleuropneumoniae, RNA, Vol:22, ISSN:1355-8382, Pages:1373-1385
et al., 2014, The Generation of Successive Unmarked Mutations and Chromosomal Insertion of Heterologous Genes in Actinobacillus pleuropneumoniae Using Natural Transformation, PLOS One, Vol:9, ISSN:1932-6203
et al., 2010, Regulation of pga operon expression and biofilm formation in Actinobacillus pleuropneumoniae by sigmaE and H-NS., Journal of Bacteriology, Vol:192, Pages:2414-2423
et al., 2009, Natural competence in strains of Actinobacillus pleuropneumoniae, FEMS Microbiology Letters, Vol:298, ISSN:0378-1097, Pages:124-130
et al., 2009, Analysis of the Actinobacillus pleuropneumoniae HlyX (FNR) regulon and identification of iron-regulated protein B as an essential virulence factor, Proteomics, Vol:9, ISSN:1615-9853, Pages:2383-2398
et al., 2008, Pasteurellaceae ComE1 proteins combine the properties of fibronectin adhesins and DNA binding competence proteins, Plos One, Vol:3
et al., 2008, Analysis of the Actinobacillus pleuropneumoniae ArcA regulon identifies fumarate reductase as a determinant of virulence, Infection and Immunity, Vol:76, ISSN:0019-9567, Pages:2284-2295
et al., 2008, The complete genome sequence of Actinobacillus pleuropneumoniae L20 (serotype 5b)., J Bacteriol, Vol:190, Pages:1495-1496