It is a matter of whether we allow microbes to enter the food chain

Even fine smelling food might still contain pathogens. Meet Professor Martin Loessner, the microLife section editor for bacteriophages, who developed new approaches to detect foodborne pathogens.

(No) lack of resistance

When Martin Loessner decided as a little boy to become a scientist, he was already showing a lot of resistance. Even during Carnival—the so-called ‘Fifth Season’ in the western parts of Germany celebrated with street parades and costume balls—he gave his mum ‘a hard time finding costumes to dress him (me) up as a researcher or explorer’. Since then, Martin followed his curiosity and studied biology in Freiburg i. Br., Germany, and Michigan, USA, and eventually embarked on a PhD at the Bacteriological Institute at the Technical University in Munich, Germany. Here, he further stayed as a postdoctoral researcher, habilitated and became an Assistant Professor.

During his early research years, he discovered his passion for bacteriophages and how they interact with their bacterial hosts. Especially, the function of the bacterial cell envelope in the uptake and release of bacteriophages fascinated him and he was at the forefront of research into endolysins (Loessner et al. 1995). These enzymes are encoded by the bacteriophage and activated at the end of the phage multiplication cycle. At that stage, new phage particles are assembled inside the bacterial cells and the bacteria start producing endolysins. With that, they decide their own fate: the endolysin recognizes the peptidoglycan of the bacterial envelope while its catalytic domain hydrolyses the cell wall from within. Together with a membrane pore-forming holin, endolysin activity destroys the host bacterium to release the newly produced phage particles (Loessner et al. 1997).

Having found ‘a new agent that works as an antimicrobial, the next question you ask is: What about resistance?’. The answer to that question was unexpected. Since endolysins target highly conserved bonds within the cell wall (Korndörfer et al. 2006), bacteria are essentially unable to modify them, which prevents them from developing resistance. As any microbiologist can imagine, the discovery of a lack of resistance to an effective antibacterial agent can be mind-blowing. So, Martin had to withstand opposing opinions from many researchers and colleagues from the field. However, up to this day, it seems to be worth the effort; researchers have not been able to find any stable bacterial resistance mechanism to endolysins.

Applying phages to improve lives

While unravelling the molecular basics of phage–host interactions and endolysin activity, it was always important for Martin that he would not ‘do fundamental research in the lab just for the textbook’. His background in food microbiology first motivated him to combat dairy pathogens. Yet, later he realized that phages could be used for many other applications. Hence, from the beginning, Martin knew that with his research he wanted ‘to improve food safety and possibly even save the lives of people infected with drug-resistant pathogens’.

Now, as a full Professor at the Institute of Food Nutrition and Health at the ETH Zurich, Switzerland, he still continues to develop bacteriophage-based approaches to detect and control pathogens. Martin decided to focus on the food pathogen Listeria monocytogenes since it still happens too often that we let this bacterium enter the food chain. When consumed, it can cause severe infections in both humans and animals termed listeriosis. This disease is associated with symptoms as a meningitis, skin or eye infection and often results in miscarriages, with a 20%–30% fatality rate. That is why many of Martin’s approved patents are for diagnostic approaches and platforms to detect L. monocytogenes at an early stage in contaminated foods (Hagens and Loessner 2014).

Additionally, Martin and his team also address other important disease-causing bacteria like Bacillus cereus, Staphylococcus aureus, Burkholderia pseudomallei, and Salmonella enterica. For example, the Gram-negative B. pseudomallei causes the life-threatening disease meliodosis that can lead to rapid death. Martin and his team developed an assay that contains latex beads coupled to the tail affinity protein of a specific bacteriophage. This simple assay can agglutinate the bacterium and detect the pathogen quickly in a sample (Muangsombut et al. 2021).

Transforming and stabilizing the system

Despite these results, Martin’s overall goal was to optimize bacteriophage-based diagnostics and control measures. Hence, for many years, his lab was looking for ways to develop a platform-like system to design and produce novel bacteriophages. They started to investigate bacterial L-forms and found that these are excellent candidates for biotechnological applications. Bacterial L-forms are cells that lost their cell walls but retain the ability to undergo cell division. So, they could be applied as ‘membrane vesicles for the transformation and expression of large DNA molecules, such as entire bacteriophage genomes’. However, as it turned out, L-form bacteria would not take up phage DNA easily and its was pure serendipity that Martin’s team discovered the right conditions to transfer large bacteriophage DNA into L-form cells. This new platform now provides them with an endless synthetic biology toolbox for creating synthetic phages (Kilcher et al. 2018).

As one can guess, these longer-term research projects were not always straight-forward and Martin had to make sure his lab members stayed motivated throughout the years. His secret formula is to establish ‘a great working and team spirit so that everyone feels comfortable and all people in the lab enjoy what they do’. He even prioritizes this over ongoing research and organizes regular social outings with his team. His motivation to ‘take proper care of the individual personalities of the people to create a comfortable atmosphere’ is actually based on the elementary rules of (microbial) ecology: diversity stabilizes the system.

Conflict of interest statement

None declared.

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