Melanie Blokesch

Melanie Blokesch holds a PhD degree from the Ludwig-Maximilians-Universität in Munich, Germany. After a postdoctoral stay at Stanford University (USA; Department of Microbiology and Immunology) she joined EPFL as a tenure-track Assistant Professor in 2009 and was promoted to Associate Professor (tenured) in 2016. In 2018, Melanie Blokesch was nominated as new member of the the Swiss National Science Foundation (SNSF) National Research Council (starting date: April 2019). Melanie Blokesch is also an elected member of the European Academy of Microbiology (EAM; since 2018) and the European Molecular Biology Organization (EMBO; since 2019). Among other awards and grants, Melanie Blokesch has been honored with the Prize for Junior Scientists of the German National Academy of Sciences Leopoldina in 2005, an ERC Starting Grant in 2012, the EPFL teaching award "Polysphère" for best teacher in the School of Life Sciences (academic year 2014-2015), the Research Award by the Association for General and Applied Microbiology (VAAM; Germany) in 2015, and an ERC Consolidator Grant in 2016. In 2017, Melanie Blokesch was awarded a Howard Hughes Medical Institute (HHMI) International Research Scholarship.

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BIO-477: Infection biology

Infectious diseases (ID) are still a major problem to human health. But how do pathogens make us sick? How do they evolve and spread? The discovery and use of antibiotics and vaccination has changed the outcome of some IDs. But resistance mechanisms have evolved and are of major concern.

BIO-666: Practical - Blokesch Lab

How to look at tiny things: visualizing protein localization in bacteria using epifluorescence microscopy.

Vibrio cholerae

Vibrio cholerae (le vibrion cholérique ou le bacille virgule en français) est une bactérie à gram négatif, en forme de bâtonnet incurvé, mobile et responsable chez l'Homme du choléra, une maladi

Compétence (biologie)

En biologie, la compétence est la capacité d'une cellule à prélever une molécule d'ADN libre dans son environnement par le phénomène de transformation. On distingue la compétence naturelle de certain

Transfert horizontal de gènes

vignette|alt=Il s'agit d'une image représentant l'arbre de la vie à 3 domaines. Des croisements entre branches de cet arbre (qui est donc en fait un réseau) indique que la transmission de matériel gén

DNA modifications impact natural transformation of Acinetobacter baumannii

Melanie Blokesch, Nicolas Jean Philippe Guex, Christian Iseli, Nina Vesel

Acinetobacter baumannii is a dangerous nosocomial pathogen, especially due to its ability to rapidly acquire new genetic traits, including antibiotic resistance genes (ARG). In A. baumannii, natural competence for transformation, one of the primary modes of horizontal gene transfer (HGT), is thought to contribute to ARG acquisition and has therefore been intensively studied. However, knowledge regarding the potential role of epigenetic DNA modification(s) on this process remains lacking. Here, we demonstrate that the methylome pattern of diverse A. baumannii strains differs substantially and that these epigenetic marks influence the fate of transforming DNA. Specifically, we describe a methylome-dependent phenomenon that impacts intra- and inter-species DNA exchange by the competent A. baumannii strain A118. We go on to identify and characterize an A118-specific restriction-modification (RM) system that impairs transformation when the incoming DNA lacks a specific methylation signature. Collectively, our work contributes towards a more holistic understanding of HGT in this organism and may also aid future endeavors towards tackling the spread of novel ARGs. In particular, our results suggest that DNA exchanges between bacteria that share similar epigenomes are favored and could therefore guide future research into identifying the reservoir(s) of dangerous genetic traits for this multi-drug resistant pathogen.

2023

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Sporadic type VI secretion in seventh pandemic Vibrio cholerae

Melanie Blokesch, Nicolas René Chiaruttini, Natalia Carolina Drebes Dörr, Sandrine Natacha Isaac, Lisa Christina Metzger, Alexis Joseph Proutière, Sandrine Stutzmann

Vibrio cholerae is a pathogen that causes disease in millions of people every year by colonizing the small intestine and then secreting the potent cholera toxin. How the pathogen overcomes the colonization barrier created by the host’s natural microbiota is, however, still not well understood. In this context, the type VI secretion system (T6SS) has gained considerable attention given its ability to mediate interbacterial killing. Interestingly, and in contrast to non-pandemic or environmental V. cholerae isolates, strains that are causing the ongoing cholera pandemic (7PET clade) are considered T6SS-silent under laboratory conditions. Since this idea was recently challenged, we performed a comparative in vitro study on T6SS activity using diverse strains or regulatory mutants. We show that modest T6SS activity is detectable in most of the tested strains under interbacterial competition conditions. The system’s activity was also observed through immunodetection of the T6SS tube protein Hcp in culture supernatants, a phenotype that can be masked by the strains’ haemagglutinin/protease. We further investigated the low T6SS activity within the bacterial populations by imaging 7PET V. cholerae at the single-cell level. The micrographs showed the production of the machinery in only a small fraction of cells within the population. This sporadic T6SS production was higher at 30 °C than at 37 °C and occurred independently of the known regulators TfoX and TfoY but was dependent on the VxrAB two-component system. Overall, our work provides new insight into the heterogeneity of T6SS production in populations of 7PET V. cholerae strains in vitro and provides a possible explanation of the system’s low activity in bulk measurements.

2023

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A single nucleotide polymorphism determines constitutive versus inducible type VI secretion in Vibrio cholerae

Melanie Blokesch, Milena Jadwiga Jaskolska, Alexis Joseph Proutière, Sandrine Stutzmann

Vibrio cholerae is a well-studied human pathogen that is also a common inhabitant of marine habitats. In both environments, the bacterium is subject to interbacterial competition. A molecular nanomachine that is often involved in such competitive behavior is the type VI secretion system (T6SS). Interestingly and in contrast to non-pandemic or environmental isolates, the T6SS of the O1 El Tor clade of V. cholerae, which is responsible for the ongoing 7th pandemic, is largely silent under standard conditions. Instead, these strains induce their full T6SS capacity only under specific conditions such as growth on chitinous surfaces (signaled through TfoX and QstR) or when the cells encounter low intracellular c-di-GMP levels (TfoY-driven). In this study, we identified a single nucleotide polymorphism (SNP) within an intergenic region of the major T6SS gene cluster of V. cholerae that determines the T6SS status of the cell. We show that SNP conversion is sufficient to induce T6SS production in numerous pandemic strains, while the converse approach renders non-pandemic/environmental V. cholerae strains T6SS-silent. We further demonstrate that SNP-dependent T6SS production occurs independently of the known T6SS regulators TfoX, QstR, and TfoY. Finally, we identify a putative promoter region adjacent to the identified SNP that is required for all forms of T6SS regulation.

2022

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