I completed my PhD at the University of New South Wales in Immunology and Medical Microbiology where I investigated bacterial immunomodulation.
I then traveled to the University of Nottingham and worked as a post-doctoral researcher with Professor Miguel Camara investigating novel drug targets and novel antibiotics to treat multi-drug resistant infections. Following this, I accepted another position with Professor Paul Williams to investigate novel murine models of biofilm formation and in vivo animal imaging.
In 2015 I accepted a position at the University of Technology Sydney with Associate Professor Cynthia Whitchurch where we investigate novel bacterial lifestyles and their interaction with the host. I am also continuing to explore my interests in drug discovery and the utilisation of small animal in vivo imaging to trace bacterial infections.
The Australasian Society of Microbiology
The Australasian Society of Immunology
The Society of General Microbiology (UK)
Can supervise: YES
I aim interested in investigating the interactions between hosts and bacterial diseases. Of particular interest is my work with Associate Professor Cynthia Whitchurch where we investigate the novel phenomenon of explosive cell lysis and how it modulates immune interaction to promote bacterial survival. We are also investigating the L-form bacteria and whether they are persistent immune silent persistent forms of bacterial life.
I am very interested in small animal imaging, particularly how it can be used to track disease and the establishment of novel insect and nematode models of infection that can be used in place of mammals in scientific testing.
I have lectured at the University of New South Wales in:
- Molecular Biology
And have contributed to the tutoring of the Epidemiology and Public Health course at the University of Technology Sydney.
See-Too, WS, Ambrose, M, Malley, R, Ee, R, Mulcahy, E, Manche, E, Lazenby, J, McEwan, B, Pagnon, J, Chen, JW, Chan, KG, Turnbull, L, Whitchurch, CB & Roddam, LF 2019, 'Pandoraea fibrosis sp. nov., a novel Pandoraea species isolated from clinical respiratory samples.', International journal of systematic and evolutionary microbiology, vol. 69, no. 3, pp. 645-651.View/Download from: UTS OPUS or Publisher's site
Pandoraea species have been isolated from diverse environmental samples and are emerging important respiratory pathogens, particularly in people with cystic fibrosis (CF). In the present study, two bacterial isolates initially recovered from consecutive sputum samples collected from a CF patient and identified as Pandoraea pnomenusa underwent a polyphasic taxonomic analysis. The isolates were found to be Gram-negative, facultative anaerobic motile bacilli and subsequently designated as strains 6399T (=LMG29626T=DSM103228T) and 7641 (=LMG29627=DSM103229), respectively. Phylogenetic analysis based on 16S rRNA and gyrB gene sequences revealed that 6399T and 7641 formed a distinct phylogenetic lineage within the genus Pandoraea. Genome sequence comparison analysis indicated that strains 6399T and 7641 are clonal and share 100 % similarity, however, similarity to other type strains (ANIb 73.2-88.8 %, ANIm 83.5-89.9 % and OrthoANI 83.2-89.3 %) indicates that 6399T and 7641 do not belong to any of the reported type species. The major cellular fatty acids of 6399T were C16 : 0 (32.1 %) C17 : 0cyclo (18.7 %) and C18 : 1ω7c (14.5 %), while Q-8 was the only respiratory quinone detected. The major polar lipids identified were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. The genomic DNA G+C content of 6399T was 62.9 (mol%). Strain 6399T can be differentiated from other members of Pandoraea by the absence of C19 : 0ω8c cyclo and by the presence of C17 : 0ω8c cyclo. Together our data show that the bacterial strains 6399T and 7641 represent a novel species of the genus Pandoraea, for which the name Pandoraea fibrosis sp. nov. is proposed (type strain 6399T).
Dubern, JF, Cigana, C, De Simone, M, Lazenby, J, Juhas, M, Schwager, S, Bianconi, I, Döring, G, Eberl, L, Williams, P, Bragonzi, A & Cámara, M 2015, 'Integrated whole-genome screening for Pseudomonas aeruginosa virulence genes using multiple disease models reveals that pathogenicity is host specific', Environmental Microbiology, vol. 17, no. 11, pp. 4379-4393.View/Download from: Publisher's site
© 2015 Society for Applied Microbiology and John Wiley & Sons Ltd. Pseudomonas aeruginosa is a multi-host opportunistic pathogen causing a wide range of diseases because of the armoury of virulence factors it produces, and it is difficult to eradicate because of its intrinsic resistance to antibiotics. Using an integrated whole-genome approach, we searched for P.aeruginosa virulence genes with multi-host relevance. We constructed a random library of 57 360 Tn5 mutants in P.aeruginosaPAO1-L and screened it in vitro for those showing pleiotropic effects in virulence phenotypes (reduced swarming, exo-protease and pyocyanin production). A set of these pleiotropic mutants were assayed for reduced toxicity in Drosophila melanogaster,Caenorhabditis elegans, human cell lines and mice. Surprisingly, the screening revealed that the virulence of the majority of P.aeruginosa mutants varied between disease models, suggesting that virulence is dependent on the disease model used and hence the host environment. Genomic analysis revealed that these virulence-related genes encoded proteins from almost all functional classes, which were conserved among P.aeruginosa strains. Thus, we provide strong evidence that although P.aeruginosa is capable of infecting a wide range of hosts, many of its virulence determinants are host specific. These findings have important implication when searching for novel anti-virulence targets to develop new treatments against P.aeruginosa.
Ee, R, Ambrose, M, Lazenby, J, Williams, P, Chan, KG & Roddam, L 2015, 'Genome sequences of two Pandoraea pnomenusa isolates recovered 11 months apart from a cystic fibrosis patient', Genome Announcements, vol. 3, no. 1.View/Download from: Publisher's site
© 2015 Ee et al. Pandoraea is an emerging respiratory pathogen capable of causing chronic lung infections in people with cystic fibrosis (CF), but the clinical significance of this infection is ambiguous. We have sequenced and annotated the genomes of two multidrugresistant Pandoraea pnomenusa isolates recovered 11 months apart from the same CF patient.
Lazenby, JJ, Griffin, P, Kyd, J, Whitchurch, CB & Cooley, M 2013, 'A Quadruple Knockout Of LasIR And RhlIR Of Pseudomonas Aeruginosa PAO1 That Retains Wild-type Twitching Motility Has Equivalent Infectivity And Persistence To PAO1 In A Mouse Model Of Lung Infection', Plos One, vol. 8, no. 4, pp. 1-10.View/Download from: UTS OPUS or Publisher's site
It has been widely reported that quorum-sensing incapable strains of Pseudomonas aeruginosa are less virulent than wild type strains. However, quorum sensing mutants of P. aeruginosa have been shown to develop other spontaneous mutations under prolonged culture conditions, and one of the phenotypes of P. aeruginosa that is frequently affected by this phenomenon is type IV pili-dependent motility, referred to as twitching motility. As twitching motility has been reported to be important for adhesion and colonisation, we aimed to generate a quorum-sensing knockout for which the heritage was recorded and the virulence factor production in areas unrelated to quorum sensing was known to be intact. We created a lasIRrhlIR quadruple knockout in PAO1 using a published technique that allows for the deletion of antibiotic resistance cartridges following mutagenesis, to create an unmarked QS knockout of PAO1, thereby avoiding the need for use of antibiotics in culturing, which can have subtle effects on bacterial phenotype. We phenotyped this mutant demonstrating that it produced reduced levels of protease and elastase, barely detectable levels of pyoverdin and undetectable levels of the quorum sensing signal molecules N-3-oxododecanoly-L-homoserine lactone and N-butyryl homoserine lactone, but retained full twitching motility. We then used a mouse model of acute lung infection with P. aeruginosa to demonstrate that the lasIRrhlIR knockout strain showed equal persistence to wild type parental PAO1, induced equal or greater neutrophil infiltration to the lungs, and induced similar levels of expression of inflammatory cytokines in the lungs and similar antibody responses, both in terms of magnitude and isotype. Our results suggest, in contrast to previous reports, that lack of quorum sensing alone does not significantly affect the immunogenicity, infectiveness and persistence of P. aeruginosa in a mouse model of acute lung infection
Skindersoe, ME, Zeuthen, LH, Brix, S, Fink, LN, Lazenby, J, Whittall, C, Williams, P, Diggle, SP, Froekiaer, H, Cooley, M & Givskov, M 2009, 'Pseudomonas aeruginosa quorum-sensing signal molecules interfere with dendritic cell-induced T-cell proliferation', FEMS Immunology and Medical Microbiology, vol. 55, no. 3, pp. 335-345.View/Download from: Publisher's site
Pseudomonas aeruginosa releases a wide array of toxins and tissue-degrading enzymes. Production of these malicious virulence factors is controlled by interbacterial communication in a process known as quorum sensing. An increasing body of evidence reveals that the bacterial signal molecule N-(3-oxododecanoyl)-l-homoserine lactone (OdDHL) exhibits both quorum-sensing signalling and immune-modulating properties. Recently, yet another quorum-sensing signal molecule, the Pseudomonas quinolone signal (PQS), has been shown to affect cytokine release by mitogen-stimulated human T cells. In the present article we demonstrate that both OdDHL and PQS decrease the production of interleukin-12 (IL-12) by Escherichia coli lipopolysaccharide-stimulated bone marrow-derived dendritic cells (BM-DCs) without altering their IL-10 release. Moreover, BM-DCs exposed to PQS and OdDHL during antigen stimulation exhibit a decreased ability to induce T-cell proliferation in vitro. Collectively, this suggests that OdDHL and PQS change the maturation pattern of stimulated DCs away from a proinflammatory T-helper type I directing response, thereby decreasing the antibacterial activity of the adaptive immune defence. OdDHL and PQS thus seem to possess dual activities in the infection process: as inducers of virulence factors as well as immune-modulators facilitating the infective properties of this pathogen. © 2009 Federation of European Microbiological Societies.
Ritchie, AJ, Whittall, C, Lazenby, JJ, Chhabra, SR, Pritchard, DI & Cooley, MA 2007, 'The immunomodulatory Pseudomonas aeruginosa signalling molecule N-(3-oxododecanoyl)-L-homoserine lactone enters mammalian cells in an unregulated fashion', Immunology and Cell Biology, vol. 85, no. 8, pp. 596-602.View/Download from: Publisher's site
The Pseudomonas aeruginosa quorum-sensing signal molecule N-3-oxododecanoyl)-L-homoserine lactone (OdDHL) has been reported to affect the function of a wide range of mammalian cell types, including cells of the immune system. In T cells, it has been reported to inhibit the production of most cytokines, and it has been reported to inhibit the function of antigen-presenting cells. The intracellular target of OdDHL in these cells remains to be identified, although the lipophilic nature of the molecule suggested that the target could be membrane associated. We explored the association of radiolabelled OdDHL with the membrane and cytoplasm of Jurkat T-cell lines and of primary murine T cells and dendritic cells. We found that not only did 3H-OdDHL enter the cytoplasm of Jurkat cells without disproportionate association with the cell membrane, it also reached maximum levels in the cytoplasm very quickly, and that the intracellular concentration was proportional to the extracellular concentration. Similar results were obtained when 3H-OdDHL was incubated with primary murine T cells or cultured dendritic cells. In addition, we show that the cellular distribution of OdDHL does not significantly alter after stimulation of Jurkat cells or primary murine CD4 T cells with immobilized anti-CD3, with little activity being associated with nuclear fractions. Together, these data strongly suggest that OdDHL enters mammalian cells by passive mechanisms, and that it does not preferentially associate with the membrane or nucleus upon T-cell receptor ligation. © 2007 Australasian Society for Immunology Inc. All rights reserved.
Lazenby, JJ & Chang, CY 2014, 'Pathogens' in Medical Sciences at a Glance, John Wiley & Sons, USA, pp. 130-133.
The definitive companion for medical science study and revision Medical Sciences at a Glance consolidates the scientific knowledge a student needs to know to provide a solid framework of key facts to build on.