Clinical pathology

Event Date: 
Wednesday, February 29, 2012 - 15:45 - 16:15
Institution: 
University of Melbourne
Title: 

Retracing the Recent Emergence of Mycobacterium ulcerans.

Abstract: 

It is more than 60 years since Mycobacterium ulcerans was shown to be the causative agent of Buruli ulcer yet it is still unclear where the bacterium resides in the environment and how it is transmitted to humans. Limited genome comparisons show that M. ulcerans has the characteristics of a niche-adapted microbe, having evolved recently from the fish-associated, opportunistic human pathogen, Mycobacterium marinum by horizontal gene transfer and reductive evolution. To further understand the relationship between these two species of pathogenic mycobacteria and to gain deeper insights into the evolution of M. ulcerans, we have used high throughput short-read DNA sequencing and compared the genomes of 30 strains of M. ulcerans and 5 strains of M. marinum, a strain collection that spans the known genetic diversity of these two species. We used a nucleotide read-mapping approach and objectively defined a 4,362,138 bp M. ulcerans-M. marinum core genome. Pairwise comparisons of every strain against this core revealed 129,416 variable nucleotide positions (3.0% nucleotide overall variation) across the two species and permitted the construction of a high resolution phylogeny for the complex, confirming that all M. ulcerans strains evolved from a common M. marinum progenitor and have diverged again into two distinct sub- lineages. In conjunction with de novo sequence assembly and gene ortholog clustering techniques, we used this phylogeny as a framework for reconstruction of a putative M. ulcerans most recent common ancestor (MRCA). We show that presence of the pMUM plasmid required for production of the polyketide toxin mycolactone (a potent immunosuppressor), high copy number of the insertion sequence IS2404, and loss/mutation of genes associated with, anaerobic respiration, lipid and cell-wall metabolism were all key attributes of the M. ulcerans MRCA before its global dispersal. Interestingly, intact genes involved with lipid metabolism and the cell wall showed evidence of positive selection with significantly higher dN/dS ratios than M. marinum strains. These data provide clues regarding the characteristics of the niche(s) M. ulcerans occupies and are guiding efforts to control the spread of Buruli ulcer.

Event Date: 
Wednesday, January 25, 2012 - 19:15 - 20:00
Institution: 
University of Technology Sydney
Title: 

The unusual life and cell cycles of extreme Archaea

Abstract: 

Environments that pose chemical and physical challenges to life generally provide a less competitive habitat to those organisms that can adapt to these “extreme” environments. Of the three domains of life, the Archaea have proven to be the most successful in this regard; some environments are almost exclusively inhabited by archaea, with few or no representatives from the bacterial and eukaryotic domains. Archaea in such environments show some unusual properties that are thought to be related to adaption or a lack of inter-species competition. My research has focussed on the molecular cell biology of two model species of extreme archaea; Sulfolobus solfataricus, which lives in sulphurous hot springs with optimal growth at around 80 C and pH 2-3, and Haloferax volcanii, which lives in high-salt environments such as the salt lakes in Australia and the “Dead” sea in Israel. Genomic and cell cycle studies of these species have shown that genetic multiplicity is a common theme in Archaea. Multiple chromosomes, DNA replication origins, and paralogs of cell-cycle related genes are evident in these species. In this seminar, I will present cell cycle and cell biological studies and I will discuss how the basic cell biological features of archaea might relate to their adaption to extreme environments.

Many scientific minds gathered together for a series of talks on a warm October evening at the Australian Museum.

The first presenter, Martin Ostrowski from Macquarie University continued from last month’s marine microbiology theme by presenting the genetics and ecology of Synechococcus. He demonstrated the distribution patterns of Synechococcus lineages are similar in different ocean systems with comparable environmental conditions. However, specific Synechococcus lineages show a distinct distribution pattern at a global scale. This finding may be useful to predict bacterial community structures in marine ecosystems.
Event Date: 
Wednesday, November 30, 2011 - 19:15 - 20:00
Institution: 
UNSW
Title: 

Rocking the cradle of life: Functional complexity of modern stromatolites.

Abstract: 
One of the major challenges in science is to identify modern living systems that present unique opportunities to address fundamental questions in diverse fields ranging from microbiology, geology, evolution, chemical biology, functional genomics, and biotechnology. The living stromatolites of Shark Bay on the western coast of Australia represent such a system. The overarching aim of our research program is to comprehensively characterise the functional complexity of modern stromatolites, in particular the diversity, biogeochemistry, and key interactions of the microorganisms forming the Shark Bay stromatolites. Understanding modern stromatolite systems is of fundamental significance to shed light on the evolution of early microbial life and the impacts of these ecosystems on both past and present global nutrient cycling.

Shark Bay is notable for its living marine stromatolites, and is listed as a World Heritage Site. In addition to their established evolutionary significance, these stromatolites, located in a hypersaline environment, are an ideal biological system for studying survival strategies of microorganisms to a range of stresses and their metabolic cooperation with other microorganisms. To further our understanding of these geobiological structures, detailed analyses of associated microbial communities and their functional characteristics are crucial.

This presentation will summarise the platform of our work over the last several years, focusing on recent discoveries and how these have led to new research directions employing a range of cutting edge technologies. This includes a comprehensive study elucidating major microbial populations, novel organism characterisation, signature lipid profiles, adaptive mechanisms of novel stromatolite isolates, creating a detailed biogeochemical profile of living stromatolites, whole genome analyses, and mechanisms of communication in these systems.

Finally, from an educational perspective, an interactive virtual field trip is being developed that will be an invaluable tool for both future research and conservation. Through the application of a rational and integrated approach, this research has provided valuable insights into these evolutionally significant biological systems. We now know who the key microbial players are, and can use this knowledge to examine specific functional characteristics to take the research to the next level, utilising the new suite of techniques now revolutionising the field of environmental microbiology.

  1. Allen MA, et al. (2010) Lipid biomarkers in Hamelin Pool microbial mats and stromatolites. Org Geochem 41, 1207-1218.
  2. Leuko S, et al. (2011) Molecular assessment of UVC radiation-induced DNA damage repair in the stromatolitic halophilic archaeon, Halococcus hamelinensis. J Photochem Photobiol B: Biology 102, 140–145.
  3. Goh F, et al. (2011) Osmoadaptive strategies of the archaeon Halococcus hamelinensis isolated from a hypersaline stromatolite environment. Astrobiology 11, 529-536.
Event Date: 
Wednesday, November 30, 2011 - 18:00 - 18:15
Institution: 
University of Technology Sydney
Title: 

Metagenomic insights into microbial community control: From the global to the microscale.

Abstract: 

The recent application of next-generation DNA sequencing tools has provided a wealth of new information about the diversity of microbial life, however the ecological factors which determine spatial patterns in prokaryotic gene abundance remain elusive. Using metagenomics and high-throughput sequencing of taxonomic marker genes, we have demonstrated shifts in microbial taxonomy and function along a salinity and nutrient gradient in the Coorong lagoon, South Australia. Functionally, genes showing the greatest response to physiochemical variability are related to salinity tolerance and photosynthesis. Taxonomically, Cyanobacteria and Archaea showed the greatest shifts in abundance along the gradient. Despite this variability however, the overall signature of metagenomic profiles remained remarkably conserved between sampling sites, and when compared to metagenomes from diverse habitats clustered with diverse sediment and soil habitats, regardless of salinity. This data indicates that the substrate type of the sample, fluid or porous, is a fundamental determinant of patterns in microbial community function globally, regardless of local chemical conditions. Whilst microbial community structure is determined on varying global and local scales, as demonstrated by the above data, the behaviour of microorganisms is determined on the microscale, with individual cells responding to gradients in specific nutrients in a patchy ecosystem. Using novel in situ sampling devices, and next-generation DNA sequencing techniques, our future work will focus on describing the microscale interactions between cells and nutrients in the ocean and how this relationship relates to ocean scale biogeochemical processes within the Carbon, Nitrogen and Sulfur cycles.

A keen crowd of about 35 braved the rain to attend the September JAMS, which this month was held within the more spacious setting of the 4th floor at the Australian Museum. This month’s presentations all had a marine flavour, with the audience enjoying three entertaining talks focussed on the community dynamics and biogeochemical capabilities of marine microorganisms.

An enthusiastic crowd of around 50 gathered to see out the winter months on the last day of August at another great JAMS meeting at the Australian Museum. The JAMS series brings together research microbiologists, including post-docs, PhD students and senior researchers, working in non-clinical projects from institutes throughout the Sydney region. The JAMS organisers would like to thank the Australian Museum for providing the fantastic venue for the meetings, as well as the Australian Society for Microbiology for sponsoring the event to provide pizza and drinks.

Event Date: 
Wednesday, August 31, 2011 - 19:15 - 20:00
Institution: 
Oregon State University
Title: 

Genomics-guided discovery of novel traits in Pseudomonas fluorescens

Abstract: 

Pseudomonas fluorescens is a diverse bacterial species known for its ubiquity in natural habitats and the production of structurally diverse, bioactive secondary metabolites. The high degree of ecological and metabolic diversity represented in P. fluorescens is reflected in the genomic diversity displayed among strains. Certain strains, such as the biological control bacterium P. fluorescens Pf-5, live in association with plants, protecting them from infection by plant pathogens. Strain Pf-5 produces an array of structurally-characterized secondary metabolites that are toxic to plant pathogenic bacteria, fungi and Oomycetes. Biosynthetic gene clusters for many of these metabolites are located in lineage-specific regions absent from the genomes of other strains of P. fluorescens. Orphan gene clusters, which encode for the biosynthesis of unknown natural products, have also been identified in lineage-specific regions of the Pf-5 genome and the following products identified through combined bioinformatic and chemical analyses. The novel cyclic lipopeptide orfamide A lyses zoospores produced by phytopathogenic Phytophthora spp. The FitD insect toxin contributes to the newly-discovered insecticidal activity of Pf-5, and several analogs of rhizoxin, a macrocyclic lactone, exhibit antifungal activity. Recently, orphan gene clusters expressed under the control of global regulators such as GacA have been identified via transcriptome analysis of Pf-5, demonstrating the value of global-regulator-based genome mining as an approach to decipher the secondary metabolome of Pseudomonas spp. We are also employing microarrays to gain a holistic view of genome expression profiles of Pf-5 living on seed surfaces, the environment where the bacterium interacts with seed-infecting fungi and Oomycetes to affect biocontrol. A series of Pf-5 mutants having deletions in one or many (up to seven) known or orphan gene clusters have been derived and are being tested in a series of bioassays. These approaches are providing new insights into the metabolic capacity of this bacterium, its activity on plant surfaces, and its interactions with plants, insects and other microorganisms.

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