In this ‘behind the paper’ post, Olga Ponomarova discusses how testing many diverse hypothesis brought them to find the relationship between apparently…
As we celebrate our 20th anniversary, Lisa Maier shares the story of how one PLOS Biology paper set the course for her research career.
Countless publications have shaped the research in my lab and some key papers have made my research career, my first group leader position and my first grant possible. But, as with so many things in life, it is the first time that remains the most memorable.
The first paper that had a decisive influence on my career was the 2007 PLOS Biology paper by Stecher et al. “Salmonella enterica serovar Typhimurium exploits inflammation to compete with the intestinal microbiota” from the laboratory of Wolf-Dietrich Hardt.
As with many pivotal moments in life, I remember the exact circumstances and every detail of the first time I read the paper. I was sitting at my desk in my student flat, in front of my laptop. A few days earlier, I had been discussing with a good friend the difficulty of finding the right dissertation topic. My undergraduate studies were packed with a wide variety of subjects, topics and methods. The idea of spending the next few years concentrating on just one seemed strange.
Guided by these reflections and in search of a suitable PhD endeavor, I came across an advertisement for a PhD position at the ETH in Zürich within the laboratory of Wolf-Dietrich Hardt. The project revolved around the concept of “colonization resistance” — a term that was entirely new to me — referencing the work by Stecher et al. As I delved into the paper, I discovered that the gut microbiome acts as a shield against pathogen colonization and, consequently, intestinal infections. The study used the model pathogen Salmonella Typhimurium to elegantly demonstrate that the virulent wild-type breaks colonization resistance by triggering and exploiting the host’s inflammatory immune response. By contrast, an avirulent Salmonella mutant, lacking the ability to elicit inflammation, can only subvert colonization resistance when intestinal inflammation is induced through alternative means such as genetic, chemical, or co-infection triggers.
I was instantly captivated. The gut microbiome had only been covered superficially in my studies. I had the feeling that a novel, largely unexplored realm with enormous potential was unfolding before me. I was intrigued by the concept that triggering the host’s immune defense can shift the balance between the protective microbiota and the pathogen in favor of the pathogen. I found myself pondering: How does Salmonella accomplish this? What molecular mechanisms underlie this phenomenon? Why haven’t the gut bacteria themselves evolved to handle inflammation? Where does the immune response falter? What determines competitiveness in the gut? Can this be leveraged to the host benefit? At the same time, I was a bit skeptical — would this topic keep me fascinated for the next 4-5 years?
I was lucky enough to receive an invitation to Zürich for an interview during the graduate selection process. In the autumn of 2009, I met Bärbel Stecher and Wolf-Dietrich Hardt and got excited not only by the science, but also by the scientists behind the work. Wolf offered me a PhD position in his lab to elucidate the role of the gut microbiome in Salmonella infections. I accepted the position. Bärbel took me under her wing and taught me all the relevant laboratory techniques. Since then, Bärbel and Wolf have become exceptional mentors and constant companions, and I have devoted the vast majority of my time to researching various aspects of the gut microbiome and colonization resistance. It has been gratifying over the years to understand better and better the strategies that Salmonella uses to colonize the already densely populated gut, through my own work, through the work of Wolf’s and Bärbel’s research groups, and also through the work of many other research teams around the world.
Clearly, I wasn’t the sole person who drew inspiration from the paper. A memory stands out from my research trip to Stanford in 2015. During this trip, a postdoc from the research group I was visiting welcomed me warmly, saying, “Ah, you collaborated with Bärbel Stecher! I absolutely adored her 2007 PLOS Biology publication! It was one of the inspirations for my PhD work in Justin Sonnenburg’s lab!” The paper served as a fantastic conversation starter and once again, marked the beginning of another friendship.
By now, the paper is one of the most cited papers by Wolf and Bärbel. I have re-read it countless times and often discovered new aspects. The topic has definitely captivated me beyond my PhD, continues to captivate me and my lab members, and I can well imagine that this will not change for the next decades. Admittedly, the topic becomes even more exciting with each new discovery. I am sure that we will discover countless more mechanisms and facets of how pathogens can outsmart the bacteria of the gut microbiome. Several of the questions I noted in the margins of my printed copy of the paper by Stecher et al. remain unanswered.
Many other publications, excellent mentors, opportunities and personal decisions influenced my further career. However, the PLOS Biology paper by Stecher et al. clearly was the very first trigger: a single paper can have a transformative impact on an individual’s academic journey. It would be wonderful if scientists received more recognition for the lasting impact their research has on future generations!
About the author
A biochemist and infection biologist by training, Lisa Maier earned her PhD from the Institute of Microbiology at ETH Zürich (Switzerland) in 2014. She conducted her postdoctoral training at EMBL Heidelberg (Germany). From 2019 onward, she has headed an independent research group at the University of Tübingen (Germany), reaching the position of full professor in 2022. ORCID: 0000-0002-6473-4762 @lab_maier