Phagosomal Rupture by Mycobacterium tuberculosis Results in Toxicity and Host Cell Death

Survival within macrophages is a central feature of Mycobacterium tuberculosis pathogenesis. Despite significant advances in identifying new immunological parameters associated with mycobacterial disease, some basic questions on the intracellular fate of the causative agent of human tuberculosis in antigen-presenting cells are still under debate. To get novel insights into this matter, we used a single-cell fluorescence resonance energy transfer (FRET)-based method to investigate the potential cytosolic access of M. tuberculosis and the resulting cellular consequences in an unbiased, quantitative way. Analysis of thousands of THP-1 macrophages infected with selected wild-type or mutant strains of the M. tuberculosis complex unambiguously showed that M. tuberculosis induced a change in the FRET signal after 3 to 4 days of infection, indicating phagolysosomal rupture and cytosolic access. These effects were not seen for the strains M. tuberculosisΔRD1 or BCG, both lacking the ESX-1 secreted protein ESAT-6, which reportedly shows membrane-lysing properties. Complementation of these strains with the ESX-1 secretion system of M. tuberculosis restored the ability to cause phagolysosomal rupture. In addition, control experiments with the fish pathogen Mycobacterium marinum showed phagolysosomal translocation only for ESX-1 intact strains, further validating our experimental approach. Most importantly, for M. tuberculosis as well as for M. marinum we observed that phagolysosomal rupture was followed by necrotic cell death of the infected macrophages, whereas ESX-1 deletion- or truncation-mutants that remained enclosed within phagolysosomal compartments did not induce such cytotoxicity. Hence, we provide a novel mechanism how ESX-1 competent, virulent M. tuberculosis and M. marinum strains induce host cell death and thereby escape innate host defenses and favor their spread to new cells. In this respect, our results also open new research directions in relation with the extracellular localization of M. tuberculosis inside necrotic lesions that can now be tackled from a completely new perspective

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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withdrawn 2017 hrs ehra ecas aphrs solaece expert consensus statement on catheter and surgical ablation of atrial fibrillation

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Christian Koller im Interview mit Sabine Bitter (Radio SRF 2 Kultur): Kritik am IOC: Wieso twittert das IOC ein Plakat aus der Nazizeit?, Radio SRF 2, 14.12.2021

Ein Tweet des Internationalen Olympischen Komitees (IOC) sorgt für Aufruhr: Er zeigt ein Nazi-Plakat der Olympischen Spiele 1936. Warum spielt das IOC mit Symbolen des Nationalsozialismus? Aus Dummheit, sagt der Historiker Christian Koller

What is Already Going On?

The third talk in the Spaces of Contestation series, “What Is Already Going On” features the Vancouver and Vienna based cultural research collective Urban Subjects.  Picking up from Jamie Peck’s previous talk in the series–on processes of urban neoliberalization and the inversion of creativity–Urban Subjects will discuss cultural possibilities and artistic tactics for our unsteady, contradictory, and unevenly developed present

Alternatives to the Housing Crisis: Case Study Vienna

The worldwide crisis of a dramatic lack of affordable housing — even in affluent cities such as Vancouver and Vienna — is part of a larger urban crisis that is based on speculation of urban land, the redistribution of wealth from the poor to the rich, and on the collectivization of losses and the privatization of gains characteristic of neoliberalism. Therefore, a politics aiming at the right to affordable housing for all is necessary in this moment. And housing, of course, is always more than itself — for we are housed in cities and thus also in infrastructural networks, power relations, public spaces, all of which are under pressure from market appropriation. In this talk, Gabu Heindl, architect and urban planner from Vienna, Austria, proposes equality, justice and the enabling of political dissensus as parameters for city planning. Using Vienna as a case study, this lecture explores the relationship of affordable housing to urban planning politics and will discuss historic and current housing policies, not least in a critical cross-analysis with the Vancouver case. Touching upon the re-articulated model function of 1920s Red Vienna, Heindl will present her approach to combining strong claims (Setzungen) in public planning with a critique of paternalistic governance and with maintaining zones of contact with popular agency. Gabu Heindl is an architect/urban planner and theorist in Vienna, Austria. Her practice (GABU Heindl Architecture) specializes in public interventions, cultural and social buildings, urban research and planning. Her current research focuses on a post-foundational theory of planning politics with regard to radical democracy in contemporary urbanism. Gabu currently teaches in the Institute for Architecture at the Academy of Fine Arts in Vienna. Since 2013, she has been president of ÖGFA (Austrian Society for Architects) and a lecturer at the Institute for Art and Architecture at the Academy of Fine Arts. She studied both in Vienna and Tokyo and did postdoctoral work at Princeton University as a Fulbright Scholar. Gabu’s practice also includes the curation of exhibitions and symposia on issues of politics in architecture and urban planning. She is the editor of Just Architecture (ERA21, 2012), Arbeit Zeit Raum (turia+kant, 2008), and anthology on the relationship of post-Fordist work and architecture, and  the co-editor of Position Alltag – Architecture in the Context of Everyday Life (HDA Verlag, 2009).  She has published in numerous architectural journals such as JAE, Umbau, ARPA, Volume, and derive