Seth-Smith, H.M.B. et al. "Phenotypic and Genomic Analyses of Burkholderia stabilis Clinical Contamination, Switzerland". Accepted by Emerg Infect Dis
Cunrath, O., ...Seth-Smith, H.M.B. (7th) et al. "Quantitative contribution of efflux to multi-drug resistance of clinical Escherichia coli and Pseudomonas aeruginosa strains". Accepted by EBioMedicine
Agnetti, J., Seth-Smith, H.M.B. et al. "Clinical impact of the type VI secretion system on virulence of Campylobacter species during infection". BMC Infect Dis 19:237
Wuethrich, D., ...Seth-Smith, H.M.B. (8th) et al. (2019) "Air-conditioner cooling towers as complex reservoirs and continuous source of Legionella pneumophila infection evidenced by genomic analysis". Eurosurveill 24(4): pii=1800192
Borel, N., ...Seth-Smith, H.M.B. (7th) et al. (2018) "Chlamydiae in human intestinal biopsy samples". Pathog Dis 76(8): fty081
Seth-Smith, H.M.B. et al. "Discovery and characterization of Mycobacterium basiliense sp. nov., a nontuberculous mycobacterium isolated from human lungs". Front Microbiol 9: 3184
Hinic, V., Seth-Smith, H.M.B. (joint 1st) et al. "First report of sexually transmitted multi-drug resistant Shigella sonnei infections in Switzerland, investigated by whole genome sequencing". Submitted to Swiss Med Weekly
Longbottom, D., ...Seth-Smith, H.M.B. (final author). "Genomic evidence that the live Chlamydia abortus vaccine strain 1B is not attenuated and has the potential to cause disease". Vaccine 36(25): 3593-3598
Qi, W., ...Seth-Smith, H.M.B. (final author). "Ca. Endozoicomonas cretensis: a novel fish pathogen characterised by genome plasticity". Gen Biol Evol 10(6): 1363–1374
Staub E., ...Seth-Smith, H.M.B. (2nd last) et al. (2018) "Novel Chlamydia species isolated from snakes are temperature-sensitive and exhibit decreased susceptibility to azithromycin". Sci Rep 8(1):5660
Last, A.R., ...Seth-Smith, H.M.B. (9th) et al. (2018) "Population-based analysis of ocular Chlamydia trachomatis in trachoma-endemic West African communities identifies genomic markers of disease severity". Genome Med 10(1):15.
Stadler, T., ...Seth-Smith, H.M.B. (6th) et al. (2018) "Transmission of ESBL-producing Enterobacteriaceae and their mobile genetic elements - identification of sources by whole genome sequencing: study protocol for an observational study in Switzerland". BMJOpen 8(2):e021823
Jahn K., Baettig V., Seth-Smith H.M.B. et al. (2018) "Rare cases of Blastobotrys raffinosifermentans as cause of FEV1 decline in two CF patients - whole genome sequencing to exclude transmission". J Cyst Fibros 7(2):e17-e19
Sommerstein, R., ...Seth-Smith, H.M.B. (6th) et al. (2017) "Burkholderia stabilis outbreak associated with contaminated commercially-available washing gloves, Switzerland, May 2015 to August 2016". Eurosurveill 22 (49): pii
Hadfield, J., ... Seth-Smith, H.M.B. (3rd) et al. (2017) "Evolutionary and recombination dynamics of Chlamydia trachomatis: recent expansions and a conspicuous absence of antibiotic resistance". Genome Res 27 (7): 1220-1229.
Seth-Smith, H.M.B. et al. (2017)"European Chlamydia abortus livestock isolate genomes reveal unusual stability and limited diversity, reflected in geographical signatures". BMC Genomics 18:344.
Seth-Smith, H.M.B. et al. (2017) "Ca. Similichlamydia in epitheliocystis co-infection of gilthead seabream gills: unique morphological features of a deep branching chlamydial family". Front Microbiol 8: 508.
Seth-Smith, H.M.B. et al. (2017)"Chlamydia suis demonstrates unprecedented genome diversity, plasticity and mobile antibiotic resistance: comparative genomics of a recent livestock cohort shows influence of treatment regimes". Genome Biol Evol 9 (3): 750-60.
Taylor-Browne, A., ...Seth-Smith, H.M.B. (2nd last) et al. (2017) "Culture-independent genomics of a novel chlamydial pathogen of fish provides new insight into host-specific adaptations utilised by these intracellular bacteria". Env Microbiol 19 (5): 1899-1913.
Wanninger, S., ...Seth-Smith, H.M.B. (6th) et al. (2016) "Selective Pressure Promotes Tetracycline Resistance of Chlamydia suis in Fattening Pigs". PLoS One 11 (11): e0166917.
Bünter, J.P., Seth-Smith, H.M.B. et al. (2016) "Naturally agr-negative livestock-associated MRSA exhibits high adhesive capacity to human and porcine cells". Res Microbiol 168 (2): 130-138.
Fehr, A., ... Seth-Smith, H.M.B. (3rd) et al. (2016) "A zebrafish model for Chlamydia infection with the obligate intracellular pathogen Waddlia chondrophila". Front Microbiol 7:1829.
Qi, W., ... Seth-Smith, H.M.B. (final author). (2016) "Host-associated genomic features of the novel uncultured intracellular pathogen Ca. Ichthyocystis revealed by direct sequencing of epitheliocysts". Genome Biol Evol (doi: 10.1093/gbe/evw111).
Andersson, P., ... Seth-Smith, H.M.B. (3rd) et al. (2016) "Chlamydia trachomatis from Aboriginal people with trachoma are from novel lineages". Nature Communications 7:10688 (doi:10.1038/ncomms10688).
Seth-Smith, H.M.B. et al. (2016) "Emerging pathogens of gilthead seabream: characterisation and genomic analysis of novel intracellular beta-proteobacteria". The ISME Journal (doi.10.1038/ismej.2015.223).
Jelocnik, M., ... Seth-Smith, H.M.B. (3rd) et al. (2016) "Molecular characterisation of the Chlamydia pecorum plasmid from porcine, ovine, bovine, and koala strains indicates plasmid-strain co-evolution". Peer J 4: e1661 (10.7717/peerj.1661).
Guevara Soto, M., ... Seth-Smith, H.M.B. (4th) et al. (2016) "The emergence of epitheliocystis in the upper Rhone region: evidence for Chlamydiae in wild and farm salmonid populations". Archives of Microbiology (doi: 10.1007/s00203-016-1192-x).
Katharios, P., Seth-Smith, H.M.B. (joint 1st author) et al. (2015) "Environmental marine pathogen isolation using mesocosm culture of sharpsnout seabream: striking genomic and morphological features of novel Endozoicomonas sp.". Scientific Reports 5: 17609 (doi:10.1038/srep17609).
Langridge, G.C., ... Seth-Smith, H.M.B. (7th) et al. (2015) "Patterns of genome evolution that have accompanied host adaptation in Salmonella". Proceedings of the National Academy of Sciences USA 112 (3): 863-8 (doi: 10.1073/pnas.1416707112).
Gillespie, S.H., ... Seth-Smith, H.M.B. (11th) et al. (2015) "Genomic investigations unmask Mycoplasma amphoriforme, a new respiratory pathogen". Clinical Infectious Diseases 60(3):381-8 (doi: 10.1093/cid/ciu820).
Seth-Smith, H.M.B. et al. (2013). "Generating whole bacterial genome sequences of low-abundance species from complex samples with IMS-MDA". Nature Protocols 8: 2404-2412 (doi:10.1038/nprot.2013.147).
Sigar, I., ... Seth-Smith, H.M.B. (6th) et al. (2013). "Plasmid deficiency in urogenital isolates of Chlamydia trachomatis reduces infectivity and virulence in a mouse model". Pathogens and Disease. (doi:10.1111/2049-632X.12086).
Seth-Smith, H.M.B. et al. (2013). "Whole genome sequences of Chlamydia trachomatis directly from clinical samples without culture". Genome Research 23(5):855-66 (doi: 10.1101/gr.150037.112).
O'Neill, C.E., Seth-Smith, H.M.B. et al. (2013). "Chlamydia trachomatis clinical isolates identified as tetracycline resistant do not exhibit resistance in vitro: whole genome sequencing reveals a mutation in porB but no evidence for tetracycline resistance genes". Microbiology 159(4): 748-756 (doi: 10.1099/mic.0.065391-0).
Seth-Smith, H.M.B., Sait, M., Sachse, K., Gaede, W., Longbottom, D., Thomson, N.R. (2013). "Genome sequence of Chlamydia psittaci strain 01DC12 originating from swine". Genome Announcements 1(1): e00078-12 (doi: 10.1128/genomeA.00078-12).
Harris, S.R., Clarke, I.N., Seth-Smith, H.M.B. et al. (2012). "Whole genome analysis of diverse Chlamydia trachomatis strains identifies phylogenetic relationships masked by current clinical typing". Nature Genetics 44: 413-9 (doi:10.1038/ng.2214).
Seth-Smith, H.M.B. et al. (2012). "Structure, Diversity, and Mobility of the Salmonella Pathogenicity Island 7 Family of Integrative and Conjugative Elements within Enterobacteriaceae". Journal of Bacteriology, 194(6): 1494-504 (doi: 10.1128/JB.06403-11).
Fookes, M., ...Seth-Smith, H. (7th) et al. (2011). "Salmonella bongori provides insights into the evolution of the Salmonellae". PLoS Pathogens, 7(8): e1002191 (doi:10.1371/journal.ppat.1002191).
Seth-Smith, H.M.B. et al. (2011). "Genome sequence of the zoonotic pathogen Chlamydophila psittaci". Journal of Bacteriology (doi:10.1128/JB.01435-10).
Unemo, M., Seth-Smith, H.M.B. et al. (2010). "The Swedish new variant of Chlamydia trachomatis: Genome sequence, morphology, cell tropism and phenotypic characterization". Microbiology, 156: 1394-1404 (doi: 10.1099/mic.0.036830-0).
He, M., ...Seth-Smith, H.M.B. (8th) et al. (2010). "Evolutionary dynamics of Clostridium difficile over short and long time scales". Proceedings of the National Academy of Sciences USA, 107: 7527-7532. (doi: 10.1073/pnas.0914322107).
Seth-Smith, H.M.B., et al. (2009). "Co-evolution of genomes and plasmids within Chlamydia trachomatis and the emergence in Sweden of a new variant strain". BMC Genomics, 10: 239 (doi:10.1186/1471-2164-10-239).
Holden, M.T.G., Seth-Smith, H.M.B. et al. (2009). "The Genome of Burkholderia cenocepacia J2315, an Epidemic Pathogen of Cystic Fibrosis Patients". Journal of Bacteriology, 191 (1): 261-277 (doi:10.1128/JB.01230-08).
Seth-Smith, H.M.B., Edwards, J., Rosser, S.J., Rathbone, D.A. and Bruce, N.C. (2008). "The Explosive-Degrading Cytochrome P450 System Is Highly Conserved Among Strains of Rhodococcus spp.". Applied and Environmental Microbiology, 74 (14): 4550-4552 (doi: 10.1128/AEM.00391-08).
Rylott, E.L., ...Seth-Smith (5th) et al. (2006). "An explosive-degrading cytochrome P450 activity and its targeted application for the phytoremediation of RDX". Nature Biotechnology, 24: 216-219 (doi:10.1038/nbt1184).
Seth-Smith, H.M.B. (2002). "Microbial degradation of RDX". Ph.D. thesis
Seth-Smith, H.M.B., Rosser, S.J., Basran, A., Travis, E.R., Dabbs, E.R., Nicklin, S. and Bruce, N.C. (2002). "Cloning, Sequencing and Characterization of the RDX Degradation Gene Cluster from Rhodococcus rhodochrous". Applied and Environmental Microbiology, 68 (10): 4764-4771 (doi: 10.1128/AEM.68.10.4764-4771.2002).
Kominami, K., Seth-Smith, H. and Toda, T. (1998). "Apc10 and Ste9/Srw1, two regulators of the APC-cyclosome, as well as the CDK inhibitor Rum1 are required for G1 cell-cycle arrest in fission yeast". EMBO Journal, 17: 5388-5399 (doi:10.1093/emboj/17.18.5388).
Seth-Smith, H.M.B. and Thomson, N.R. (2013). "Whole genome sequencing of bacterial STI pathogens: implications for clinicians". Current Opinion in Infectious Diseases 26(1):90-8 (doi: 10.1097/QCO.0b013e32835c2159).
Seth-Smith, H. (2013). "Playing the 'Next-Generation Game'". Nature Reviews Microbiology, 11:74 (doi:10.1038/nrmicro2956).
Seth-Smith, H. (2012). "Beyond the palaeomicrobiology". Nature Reviews Microbiology, 10:240 (doi:10.1038/nrmicro2768).
Seth-Smith, H. (2011). "Genome Watch: Pneu tricks". Nature Reviews Microbiology, 9:230 (doi:10.1038/nrmicro2547).
Rylott, E.L., ...Seth-Smith, H.M. (4th) et al. (2010). "The explosive-degrading cytochrome P450 XplA: biochemistry, structural features and prospects for bioremediation". Biochimica et Biophysica Acta, 1814 (1):230-6 (doi:10.1016/j.bbapap.2010.07.004).
Seth-Smith, H. (2010). "Genome Watch: 'Slick' operation". Nature Reviews Microbiology 8:538 (doi:10.1038/nrmicro2407).
Seth-Smith, H. and Croucher, N.J. (2009). "Genome Watch: Breaking the ICE". Nature Reviews Microbiology, 7:328-329 (doi:10.1038/nrmicro2137).
Seth-Smith, H.M.B. (2008)."SPI-7: Salmonella's Vi-Encoding Pathogenicity Island". Journal of Infection in Developing Countries, 2 (4): 267-271.
Seth-Smith, H. and Walker, A. (2008). "Genome Watch: Opportunity knocks". Nature Reviews Microbiology, 6:652-653 (doi:10.1038/nrmicro1985).
Seth-Smith, H. (2008). "Genome Watch: A poultry existence". Nature Reviews Microbiology, 6:8 (doi:10.1038/nrmicro1830).
Walker, A. and Seth-Smith, H. (2007). "Genome Watch: Urbane decay". Nature Reviews Microbiology, 5: 748-749 (doi:10.1038/nrmicro1763).
Seth-Smith, H. (2007). "Genome Watch: A more convenient truth". Nature Reviews Microbiology, 5: 248-250 (doi:10.1038/nrmicro1644).
Seth-Smith, H. (2007). "Genome Watch: Ocean's elevenses". Nature Reviews Microbiology, 5: 9 (doi:10.1038/nrmicro1589).
Seth-Smith, H. and Bentley, S. (2006). "Genome Watch: Where there's muck there's microbes". Nature Reviews Microbiology, 4: 646-647 (doi:10.1038/nrmicro1497).
Seth-Smith, H. (2017). "Chlamydia trachomatis: evolution and epidemiology ". Presented at NGS symposium: Whole Genome Sequencing for Clinical Microbiology - Translation into routine applications, Basel. (Invited speaker.)
Seth-Smith, H., Meinel, D. Blanc, D., Abdelbary, M., Droz, S., Fuehrer, U., Casanova, C., Lang, C, Dubuis, O., Schlegel, M., Sommerstein, R., Widmer, A., Keller, P., Marschall, J., Egli, A. (2017). "Burkholderia stabilis outbreak associated with contaminated wash gloves: description and genome sequence of an opportunistic pathogen. Presented at Joint annual meeting 2017 of SSM, SSI, SSHH, SSTMP, SSTTM, Basel.
Seth-Smith, H., Meinel, D. Blanc, D., Abdelbary, M., Droz, S., Fuehrer, U., Casanova, C., Lang, C, Dubuis, O., Schlegel, M., Sommerstein, R., Widmer, A., Keller, P., Marschall, J., Egli, A. (2017). "Burkholderia stabilis outbreak associated with contaminated wash gloves: description and genome sequence of an opportunistic pathogen". Presented at ECCMID, Vienna.
Seth-Smith, H., Harris, S., Schlapbach, R., Vaughan, L., Thomson, N. (2015). "Whole-genome sequencing of Chlamydia directly from clinical samples". Presented at ESCCAR Conference, Lausanne. (Invited speaker.)
Seth-Smith, H., Katharios, P., Dourala, N., Fehr, A., Ruetten, M., Nufer, L., Schlapbach, R., Vaughan, L. (2014). "Chlamydial agents of epitheliocystis: a cautionary tale". Presented at Australian Chlamydia Conference, University of the Sunshine Coast, Australia. (Invited speaker.)
Seth-Smith, H., Sait, M., Livingstone, M., Harris, S., Thomson, N., Longbottom, D. (2014). "The contrast in Chlamydia: a genomic survey of European Chlamydia abortus". Presented at Australian Chlamydia Conference, University of the Sunshine Coast, Australia. (Invited speaker.)
Seth-Smith, H., Katharios, P., Dourala, N., Fehr, A., Ruetten, M., Nufer, L., Schlapbach, R., Vaughan, L. (2014). "Novel epitheliocystis agents in Sparus aurata and Diplodus puntazzo investigated using detailed molecular tools". Presented at Aquaculture Europe 14 (European Aquaculture Society), San Sebastian, Spain.
Seth-Smith, H.M.B., Harris, S.R., Thomson, N.R., Schlapbach, R., Vaughan, L. (2014). "Sequencing bacterial genomes from clinical samples without cultivation". Presented at Microbiology and Infection (DGHM-VAAM), Dresden, Germany. (Invited speaker.)
Seth-Smith, H.M.B., Harris, S.R., O'Neill, C., Parmar, S., Skilton, R., Jalal, H., Clarke, I.N. and Thomson, N.R. (2012). "Sequencing the genome of Chlamydia trachomatis directly from clinical samples". Presented at 7th Meeting of the European Society for Chlamydia Research, Amsterdam, Netherlands.
Seth-Smith, H.M.B., Harris, S.R., Croucher, N., Mutreja, A., Connor, T., Bentley, S., Thomson, N., Parkhill, J. (2012). "Pathogen Genomics". Presented at What can DNA do for you?: DNA technology and applications, SCI, London, U.K.
Seth-Smith, H.M.B., Harris, S.R., Parmar, S., Skilton, R., Jalal, H., Clarke, I.N. and Thomson, N.R. (2011). "Chlamydia trachomatis: whole genomes from clinical swabs". Presented at the Applied Bioinformatics & Public Health Microbiology conference, Hinxton Conference Centre, U.K.
Seth-Smith, H.M.B., Fookes, M.C., Okoro, C., Parkhill, J., Thomson, N.R. (2010). "A family of integrative and conjugative elements in Salmonella, including SPI-7". Presented at the ASM conference on Mobile DNA, Montreal, Canada, S2:8.
Seth-Smith, H.M.B., Okoro, C., Thomson, N.R., Parkhill, J. (2009). "Salmonella pathogenicity island SPI-7 is an integrative and conjugative element with a close relative in Salmonella bongori". Presented at the ASM conference on Salmonella, Aix-en-Provence, France, 35A. [Poster]
Seth-Smith, H.M.B., Holden, M., and Parkhill, J. (2006). "Mobile Elements within the Burkholderiaceae". Presented at the ASM conference on Mobile DNA, Banff, Alberta, Canada, A55. [Poster]
Seth-Smith, H.M.B., Dennis, A., Holden, M., Crossman, L.C., Mahenthiralingham, E. and Parkhill, J. (2005). "Comparative Genomics for the Identification of Virulence Factors in Burkholderia cepacia complex" Presented at the International Conference on Microbial Genomes, Halifax, Nova Scotia, Canada. [Poster]
Edwards, J., Seth-Smith, H.M.B, Rathbone, D.A. and Bruce, N.C. (2005). "Biodegradation of the high explosive RDX by Rhodococcus sp." Presented at the SGM 156th meeting, Heriot-Watt University, Edinburgh, U.K.
Seth-Smith, H.M.B., Dennis, A., Mahenthiralingam, E. and Parkhill, J. (2004). "Comparative genomics for the identification of virulence factors in Burkholderia cepacia complex". Presented at the International Burkholderia cepacia Working Group, 9th Annual meeting, Vancouver, A13.
Seth-Smith, H.M.B., Dennis, A., Mahenthiralingam, E. and Parkhill, J. (2003). "Comparative genomics for the identification of virulence factors in Burkholderia cepacia" Presented at the Burkholderia Genomes Workshop, Hinxton Conference Centre, U.K. [Poster]
Seth-Smith, H.M.B., Rosser, S.J., Basran, A., Nicklin, S. and Bruce, N.C. (2001). "Biodegradation of RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine) by Rhodococcal species". Presented at the ASM conference on Biodegradation, Biotransformation and Biocatalysis, San Juan, Puerto Rico, A42. [Poster]
Department of Biomedicine, University of Basel, Switzerland. "Using genomics to study the evolutionary strategies of pathogens". (2016)
Institute of Veterinary Pathology, University of Zürich, Switzerland. "Looking in the wrong place: the novel bacteria causing fish gill disease". (2014)
Computational Evolution Group, D-BSSE, ETH Zürich, Basel, Switzerland. "Bacterial Infections in Aquaculture: Causative Agents & Genomic Analysis ". (2014)
Hellenic Centre for Marine Research, Crete, Greece. "Epitheliocystis Pathogens: Identifying Novel Agents and In-depth Genomic Investigation". (2014)
Institute of Veterinary Pathology, University of Zürich, Switzerland. "Genomic epidemiology hooking into uncultured fish pathogens". (2013)
Swiss Tropical and Public Health Institute, Basel, Switzerland. "Investigating pathogen diversity using high throughput genome sequencing". (2012)
Biozentrum, University of Basel, Switzerland. "Investigating pathogen diversity using high throughput genome sequencing". (2012)
Mobile Elements within the Burkholderiaceae (2006)
Seth-Smith, Helena M.B., Matthew
Holden, Julian Parkhill.
Pathogen Sequencing Unit, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, U.K.
The genus Burkholderia, formerly described as Pseudomonas, contains in excess of 30 species, which occupy a wide range of ecological niches. They have been reported as soil organisms, plant root colonisers, biocontrol agents, bioremediation agents and pathogens of plants, animals and humans. B. mallei and B. pseudomallei are category B biothreat agents, causing glanders and meliodosis, respectively, and some members of the B. cepacia complex are considered to be opportunistic human pathogens. Many Burkholderia genomes, each of which comprise multiple replicons, are in the process of being sequenced. Five of these have been completed and released, covering four different species. In addition, the high coverage shotgun sequencing of microbes from the Sargasso Sea identified a species which is a member of the Burkholderiaceae. A wealth of data now exists, from which information on mobile DNA elements can be extracted. The importance of IS elements in the evolution and diversification of Burkholderia is discussed. It has already been shown that many of the phenotypic differences between B. pseudomallei and B. mallei can be attributed to the expansion of IS elements in the latter, causing extensive genome rearrangements and gene inactivation. In this case, the effects of mobile elements within the genome are very clear. The consequences of mobile element insertion within other Burkholderia sp. genomes may not be so extreme, but may cause subtle changes in gene expression which may be related to the lifestyle of the organism. The prevalence and effect of group I and group II introns within the Burkholderiaceae will also be discussed.
Comparative Genomics for the Identification of Virulence Factors in
Burkholderia cepacia complex (2005)
Seth-Smith, Helena M.B.1*, Alison Dennis1*, Matthew
Holden1, Lisa C. Crossman 1, Eshwar
Mahenthiralingham2, Julian Parkhill1.
1Pathogen Sequencing Unit, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, U.K.
2Cardiff School of Biosciences, Cardiff University, Cardiff, Wales, U.K.
*Presenting authors.
The Burkholderia cepacia complex of bacteria contains ten species (previously genomovars) with a wide range of phenotypes. Several species, most notably B. cenocepacia (GIII) and B. multivorans (GII) are significant human pathogens, of particular concern to immunocompromised patients, or those with cystic fibrosis (CF). Others, such as B. ambifaria (GVII) are rarely encountered in clinical situations, but are widespread in the natural environment where they have been shown to act as biopesticidal agents. The genetics of the Burkholderia cepacia complex have not been characterised; in particular the pathogenesis of B. cepacia infection is not well understood and few virulence factors have been identified. The genome of Burkholderia cenocepacia strain J2315 has been sequenced at the Wellcome Trust Sanger Institute and is currently being annotated. It consists of three replicons (and one plasmid), with the smaller replicons being more associated with accessory functions. In addition to the sequencing project, differential genomic DNA hybridisation is being used to compare Burkholderia cenocepacia strain J2315 with strains of B. multivorans and B. ambifaria. This technique allows the isolation of DNA which is uniquely present or absent in each strain. These regions will then be characterised and used to provide an insight into the phenotypic differences between species. We present preliminary annotation of putative virulence-associated regions from Burkholderia cenocepacia strain J2315 as well as preliminary data from the comparisons between Burkholderia cepacia complex species.
Royal Demolition Explosive (RDX) is an important and widely manufactured high explosive but is now a recognised environmental pollutant owing to its toxicity and recalcitrance. Concern is growing regarding the large areas of land and ground water contaminated worldwide as a result of the continued manufacture, use and disposal of this compound. We have isolated 19 strains of bacteria belonging to the genus Rhodococcus that are capable of growth on RDX as a nitrogen source. We have cloned the two genes responsible for RDX degradation from R. rhodochrous strain 11Y, shown to be a highly unusual cytochrome P450, xplA and its partner oxidoreductase, xplB. Investigations of the remaining strains using a P450 inhibitor (metyrapone) greatly reduced RDX degradation suggesting P450 involvement in these strains. Furthermore, by using a combination of Southern Hybridisations and PCR, we have evidence to show that the xplA and xplB genes are present in both our RDX degrading strains, and in other strains isolated from different geographical sites from the UK and Australia. Interestingly, the homologues cloned thus far have a remarkable degree of similarity to one another (>99% amino acid identity).
Strains belonging to the Burkholderia cepacia complex are significant human pathogens, particularly causing infectious disease in patients with cystic fibrosis (CF). The pathogenesis of B. cepacia complex infection is not well understood and few virulence factors have been identified to date. The B. cepacia complex consists of at least ten distinct species. The virulence and transmissibility of each species is variable, although all are capable of causing infections in CF patients. Burkholderia cenocepacia the most predominant clinical species, is frequently found to be highly transmissible, virulent and is associated with a poor prognosis in CF patients. Strains of B. multivorans are the second most prevalent in CF sufferers and can also be virulent and transmissible. However, strains of B. ambifaria are rarely encountered in clinical situations, leading to the suggestion that they are significantly less virulent than B. cenocepacia and B. multivorans.
A comparative genomic technique was used in order to identify regions associated with pathogenesis, and to complement the genome sequence of B. cenocepacia strain J2315, currently being completed. The genetic differences between strain J2315 and the following strains were investigated: B. multivorans strain C1576 (Glasgow epidemic strain) and B. ambifaria strain AMMD (LMG 19182, a plant-associated bio-control strain). Differential genomic DNA hybridisation was performed on macroarrays to identify DNA which is uniquely present or absent in each strain. Preliminary results indicate several genes present in B. ambifaria which are absent from, or significantly different in, the sequenced strain J2315. The extent of these insertions will be determined, and the prevalence of these regions within further clinical isolates will be investigated. The results of this may lead to the further investigation of putative virulence factors by site-directed mutagenesis and infection model testing. In this way the information provided by the genome sequencing project can be employed, and novel B. cepacia complex virulence genes can be rapidly investigated.
Strains of Burkholderia cepacia are significant human pathogens, particularly causing infectious disease in patients with cystic fibrosis (CF). To date, the pathogenesis of B. cepacia infection is not well understood and few virulence factors have been identified. Nine genomovars of B. cepacia have been identified, each with distinct patterns of virulence and transmissibility. Genomovar III strains are the most predominant clinical species, being highly transmissible, highly virulent and associated with a poor prognosis in CF patients. Strains of genomovar II, also known as Burkholderia multivorans, are the second most prevalent in CF, whereas those of genomovar VII (B. ambifaria) are rarely encountered in clinical situations and are thought to be significantly less virulent. To complement the data being gathered through sequencing the genome of a genomovar III strain, and to identify regions associated with pathogenesis, a comparative genomic technique is proposed, in order to investigate differences between the genomes of B. cepacia from genomovars II, III and VII. Differential genomic DNA hybridisation will be performed to isolate DNA which is uniquely present or absent in each strain. The prevalence of these regions within further clinical isolates will be investigated, and the regions characterised using either the genome sequence data or direct sequence analysis. The results of this may lead to the further investigation of putative virulence factors by site directed mutagenesis and infection model testing. In this way the information provided by the genome sequencing project can be employed and novel B. cepacia virulence genes can be rapidly investigated.
Large amounts of land and groundwater are contaminated with explosives as a result of their manufacture and disposal. Explosives are xenobiotic compounds, highly recalcitrant in the environment, and have been shown to be toxic to biological systems. One of the main pollutants is RDX. Current methods used for the remediation of contaminated sites are uneconomical and there is evidence that toxic compounds remain. Both these problems could be addressed with the development of a biodegradation-based system. Previous work has demonstrated biotransformation of RDX by anaerobes and mixed cultures. Selective enrichments were performed on cultures from RDX contaminated soils, which resulted in the isolation of 21 strains of bacteria that possess the ability to utilise RDX as a sole nitrogen source for growth. The bacterial strains were investigated using 16S rDNA analysis and were identified as species of Rhodococcus and Phyllobacterium. One strain, identified as Rhodococcus rhodochrous, was chosen for further investigation. The products of RDX degradation by this strain have been identified and indicate the potential for mineralisation of RDX. Genetic studies are underway to determine the basis for the ability of this strain to degrade RDX.
Last updated: March 2019
Helena Seth-Smith, Basel, Switzerland
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