Living a bacterial lifestyle as an academic researcher

About the scientific life of Melanie Blokesch


Establishing a niche
In Lausanne, Melanie became interested in the DNA uptake machinery of this pathogen (Seitz and Blokesch 2013). In a study that she considers 'one of the most complete and elegant work from [my] her lab', her team unravelled how a periplasmic protein translocates foreign DNA across the outer membrane (Seitz et al. 2014). They also started investigating how V. cholerae adheres to and settles down on biotic surfaces in their natural aquatic environments. With that new research focus, she and her team found a link between the pathogen's killing weapon and its competence machinery. It was already known that those V. cholerae strains that are not responsible for the currently ongoing 7th pandemic of cholera use their antibacterial Type 6 Secretion System to fire lethal toxins into neighbouring competitors. And if these competitors-either bacteria or amoeba-were lacking the corresponding immunity proteins to the fired toxin, they are unlikely to survive the attack. To the surprise of the microbiology community, pandemic V. cholerae strains co-regulate their Type 6 Secretion System with the competence regulon when growing on chitinous surfaces. In this major publication, Melanie and her team suggested that V. cholerae would first get rid of microbial competitors by killing them and then take up the dead microbe's DNA (Borgeaud et al. 2015).
But V. cholerae is not able to kill them all. Interestingly, some bacteria living in the intestinal tracts of animals are resistant to V. cholerae's Type 6 Secretion System attacks. These bacteria might contribute to the colonization barrier that usually protects the host from the devastating cholera disease. Melanie and her team explored the underlying mechanisms of this resistance strategy. They found that members of the Enterobacter cloacae complex and the Klebsiella genus achieved resistance against Vibrio's Type 6 Secretion System attacks without the help of immunity proteins. Indeed, these human gut commensals rely on superior molecular weapons or their capsular polysaccharides as physical barriers around their cells-a new defensive mechanism within microbial communities (Flaugnatti et al. 2021).
Learning more and more about how V. cholerae settles down in its environment, this very same research topic helped Melanie establish her own niche within the Vibrio community. As an independent researcher, always having her previous projects in mind, Melanie then 'extended the research topics based on interesting experimental observations and open questions that [she] identified in the literature'. Hence, with more incoming grants, she could tackle a larger array of topics and spread out to new directions over the years. Eventually, this success led to her election to prestigious societies like the European Academy of Microbiology (EAM), European Molecular Biology Organisation (EMBO), the German National Academy of Sciences Leopoldina and the American Academy of Microbiology (AAM).

Interacting with the environment
Yet, being a full professor didn't mean for Melanie to leave the lab bench, since she enjoys the immediate and quick results from experiments. Indeed, she still 'checks plates in the incubator in the morning before even having [her] first coffee' and works closely with her technician who's performing experiments under her guidance. Melanie even says that 'what seemed annoying as a student or postdoc, such as pouring agar plates or re-streaking hundreds of colonies, becomes almost meditation as a PI'. One can also follow that passion on her Twitter account, where every now and then she publishes photos or anecdotes from her recent lab experiences.
That passion and persistence also led Melanie to her most recent large project. She finally decided to tackle a problem that has been keeping her puzzled for many years. Ever since she started working with V. cholerae, she realised that while this bacterium has no issues taking up free foreign DNA, it 'doesn't do so well with plasmids'. However, her mindset taught her-and now she teaches her lab members the same: 'don't just look for the expected results and be disappointed when things turn out in a different way; because that's often when the more interesting findings emerge that you should definitively follow up on'. Even though she usually told new lab members to avoid plasmids and add everything onto the chromosome, it was always in the back of her mind that something must be going on. During her postdoc, she already 'saw some weird morphological changes in plasmid-carrying V. cholerae when imaged during exponential phase'.
Then, after a general discussion with a friend and colleague on Vibrios, she had two lab members 'taking on the challenge to actually address the question of why plasmids are badly tolerated' by V. cholerae. After testing many different strains, they showed that it is 'exclusively the 7th pandemic clade of V. cholerae that doesn't tolerate plasmids' and they managed to unravel the molecular mechanisms behind it. This study was recently published (Jakólska et al. 2022) and shows once again that the unexpected often results in the most exciting discoveries. Having studied V. cholerae and its abilities to acquiring genetic material and establishing a niche, Melanie has finally tools to engineer new strains to study them. Hopefully, this will bring us closer to understanding this devastating bacterium and the disease it causes! Conflict of interest statement. The author was commissioned by the Federation of European Microbiological Societies (FEMS) to write this article.