Dear Listeria, what is your preferred niche?

Abstract

Seeing Pascale Cossart in one of her many science outreach videos online, one can usually recognize two major features: a lot of scientific expertise and a big smile. Both stem from her experience of being a microbiologist and her passion for the field. After her PhD in chemistry at the University of Paris, Pascale came across the microbial world by studying protein–DNA interactions. She learned about microbial physiology and started to study how microbes interact with their hosts. She then got more and more fascinated by microbes and the fact that they ‘are not only everywhere, but they are absolutely critical for the equilibrium of the human body, animals, plants, insects and the environment’. From early on, Pascale decided to focus on the Gram-positive pathogen Listeria monocytogenes, which can live silently in the gastro-intestinal tract of some healthy humans. However, in immuno-compromised people, newborns, elderly, or pregnant women, it can lead to severe infections and meningitis, encephalitis, or even miscarriage. Pascale was the first to sequence the hlyA gene, which encodes listeriolysin O—a major virulence factor— in Listeria. Together with her team, Pascale then discovered internalin, the protein that allows Listeria to enter mammalian cells, as well as its receptor on mammalian cells, the protein E-cadherin. She then became interested in how Listeria would enter host cells, and she identified many important key molecules whose role in bacterial cell entry had never been suspected. Her work on Listeria specificity for human cells versus murine was remarkable and led to the generation of a transgenic animal model for human listeriosis. As an early-stage Professor at the Institut Pasteur in Paris, Pascale made a discovery that ‘triggered a whole tsunami in the field’. She discovered the mechanisms of how L. monocytogenes uses the actin of a host to move and spread across tissue. Once inside the cytosol of the host cell, the bacterial surface protein ActA nucleates and polymerizes actin and recruits other proteins to these actin filaments (Kocks et al. 1992). Through this polymerization process, ActA triggers the formation of long actin tails and ultimately of bacteria-containing membrane protrusions. These help L. monocytogenes contact and enter neighbouring cells without ever leaving the host cytosol (Lecuit et al. 2001). Thanks to growing techniques like fluorescence microscopy, Pascale and her team managed to visualize these microbe-induced processes and establish herself in the field of infection microbiology.