Talk and poster at Final Scientific Conference of ImResFun
The BiMM robots alow efficien high throughput analysis of growth phenotypes. We investigated growth under diverse conditions of 240 C. galbrata strains originating from the Vienna General Hospital. The results were presensted at the Final Scientific Conference of ImResFun.
Talk and poster with the title:
The broad and malleable phenotypic space of clinical Candida glabrata strains. A high throughput mapping of phenotypes reveals highly
individualistic adaptations to a fluctuating environment.
Candida glabrata is a successful commensal and able to adapt to a variety of environmental situations and a cause of vulvo-vaginal candidiasis and shows high resistance to azole antifungals. To explore how this flexibility is possible, we investigated the phenotypic variation of several hundred C.glabrata clinical isolates collected by the Vienna General Hospital. Our quantitative high-throughput determination of growth parameters revealed a broad variation of phenotypes. For example temperature influenced growth rate in an unexpected range. We found that many strains tolerated either higher or
lower temperatures while all strains had a temperature optimum at around 39°C. The collection was also scored for resistance to low pH, weak
acid, osmotic stress, carbon source utilization and resistance to antifungals. Interestingly, the population spread for heat stress resistance while it remained confined for osmitic stress. This argues for the polygenetic basis of heat stress versus only few key processes contribute to osmotic stress.
Furthermore, about 15% of these strains are efficiently forming biofilms. We further investigated the stability of some phenotypes. We tried
to manipulate fluconazole resistance by adapting sensitive strains to intermediate fluconazole concentrations. This succeeded but lead to a simultaneous post-adaption loss of growth rate on rich medium, indicating that adaptation to fluconazole comes at a cost. Genome sequencing of selected phenotypically eye-catching strains revealed that their genomic profiles differed in up to 105 bases making specific assignments difficult.
For stress resistance we analyzed the general role of CgHog1 and found a widely differing spectrum of basal Hog1 phosphorylation and stress response rates. The overall change of CgHog1 phosphorylation correlated with stress resistance of the particular strains. We conclude that these C. glabrata clinical isolates exhibit a broad phenotypic spectrum. Further investigation of the genetic and epigenetic basis of these variations and their stability are required to understand the success of C. glabrata as an opportunistic commensal.
Christoph Schüller, Reinhard Beyer, Birgit Willinger, Joseph Strauss
1 Universität für Bodenkultur, Konrad Lorenz Strasse 24, Tulln a.d.
Donau 3430, Austria
2 Medizinische Universität Wien, Klinische Abteilung für Klinische
Mikrobiologie Währinger Gürtel 18-20, Wien
Publikation: Butyrate influences intracellular levels of adenine and adenine derivatives in the fungus Penicillium restrictum
Zutz C, Chiang YM, Faehnrich B, Bacher M, Hellinger R, Kluger B, Wagner M, Strauss J, Rychli K (2017)
Microbiol Res. 2017 Apr;197:1-8. doi: 10.1016/j.micres.2016.12.013. Epub 2017 Jan 11.
Butyrate, a small fatty acid, has an important role in the colon of ruminants and mammalians including the inhibition of inflammation and the regulation of cell proliferation. There is also growing evidence that butyrate is influencing the histone structure in mammalian cells by inhibition of histone deacetylation. Butyrate shows furthermore an antimicrobial activity against fungi, yeast and bacteria, which is linked to its toxicity at a high concentration.
⇒ weiterlesen: http://dx.doi.org/10.1016/j.micres.2016.12.013
BiMM Poster Presentation at ÖGMBT Annual Meeting
8th ÖGMBT Annual Meeting – Life Sciences for the Next Generation – 2016, Graz, Austria.
Poster Title: The open research platform „BiMM -Bioactive microbial metabolites“ – a high-throughput biotic and chemical interaction approach to discover novel bioactive compounds
Abstract: Novel metabolic products are needed for health and biotechnology. Production of metabolites of axenic cultures has been exploited in the last decades. More recently, it has been realized that interactions of microorganisms can lead to production of dormant enzyme activities and even the exchange of metabolites between organisms can occur. Thus co-culture of microorganisms leads to a multitude of new biosynthetic possibilities. Moreover, mass sequencing results of microbial genomes predict a much richer diversity of microbial metabolites than previously anticipated. The exploitation of the potential of this microbial genetic
dark matter has recently moved again into focus. Here we report on our approach to discover and characterize bioactive compounds and enzymes. We are using a variety of environmental and chemical conditions in which biotic interactions between different microbial genera trigger production of novel metabolites. Bioactivity testing of produced metabolites, enzymes, effectors and other compounds is performed in a
high-throughput format using automated liquid and solid handling systems. Possible hits are followed up and characterized using a metabolomics platform developed at the Center for Analytical Chemistry. We have screened in a pilot study approximately 15k co-cultures of different bacteria and fungi combinations. Among these we identified about 30 interactions producing extracts with antibacterial and antifungal activity. Identification of the compounds responsible activity is under way.
The newly created HTP infrastructure is designed as open research platform providing hardware and expertise for dedicated collaborative projects in the field of innovative bioactive metabolite and enzyme production and characterization of their properties and function.
Christoph Zutz 1, Christoph Schüller 2, Roland Hellinger 3, Kathrin Rychli 1, Martin Wagner 1, Rainer Schumacher 3, Scot Wallace 2, Joseph Strauss 2
1 Institute of Milk Hygiene, Milk Technology and Food Science, VETMED
2 Department of Applied Genetics and Cell Biology, BOKU
3 Center for Analytical Chemistry, BOKU
BiMM Vortrag auf der ICAR 2016 in Spanien
ICAR – the IV International Conference on Antimicrobial Research 28.6.2016 bis 1.7.2016 in Malaga, Spanien
Die BiMM war auf der diesjährigen ICAR mit einem Vortrag vertreten und stellte den Chair für die Session „Antimicrobial natural products II – Terrestrial and marine organisms“. Auf der dreitägigen Konferenz wurden Ergebnisse und Trends aus der Antimikrobiota Forschung, aus Industrie und akademischer Forschung, vorgestellt. Ein Schwerpunkt lag dabei auf antimikrobiellen Polymeren und Machbarkeitsstudien für deren mögliche Applikation. Die BiMM präsentierte Ergebnisse aus der laufenden Forschung an filamentösen Pilzen und identifizierten Stoffwechselprodukten dieser Pilze.
⇒ ICAR: http://www.icar-2016.org/
Lange Nacht der Forschung
Die BiMM präsentiert ihre Roboter bei der Langen Nacht der Forschung einem breiten Publikum. Rund 1000 Besucher haben die BiMM besucht und sich ihr persönliches „NÖ“ gespottet.
Publikation: Valproic Acid Induces Antimicrobial Compound Production in Doratomyces microspores
Zutz, C., Bacher, M., Parich, A., Kluger, B., Gacek-Matthews, A., Schuhmacher, R., … Strauss, J. (2016). Valproic Acid Induces Antimicrobial Compound Production in Doratomyces microspores. Frontiers in Microbiology, 7, 510.
One of the biggest challenges in public health is the rising number of antibiotic resistant pathogens and the lack of novel antibiotics. In recent years there is a rising focus on fungi as sources of antimicrobial compounds due to their ability to produce a large variety of bioactive compounds and the observation that virtually every fungus may still contain yet unknown so called “cryptic,” often silenced, compounds.
Feierliche Eröffnung der BiMM am Universitäts- und Forschungszentrum Tulln
Im Rahmen einer Festveranstaltung wurde am Universitäts- und Forschungszentrum Tulln die Core Facility und Forschungsplattform BiMM (Bioactive Microbial Metabolites) von Landeshauptmann Dr. Erwin Pröll und Sektionschef Mag. Elmar Pichl im Beisein von Univ.-Prof. DI Dr. Dr.h.c.mult. Martin Gerzabek, Rektor der Universität für Bodenkultur Wien (BOKU), Dr. Sonja Hammerschmid, Rektorin der Veterinärmedizinischen Universität Wien (Vetmeduni), und dem wissenschaftlichen Leiter Univ.-Prof. Dr. Josef Strauss eröffnet.