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Less vulnerable as a community - Timon Baltisberger wins master’s prize for analysis of biofilms
Timon Baltisberger is to receive the prize for the best master’s thesis in nanosciences at the University of Basel in 2022. In the prizewinning thesis, he proved that Vibrio cholerae bacteria inside a biofilm are more tolerant to various antibiotics than cultures grown in agitated liquid medium. The results help to improve our understanding of biofilms, which play a major role in nature and can lead to stubborn infections in humans.
In nature, bacteria are not generally present as individual organisms. Instead, they often live in communities, embedded in an extracellular matrix that allows them to exchange metabolic products and provides better protection against environmental influences.
What is beneficial for bacteria turns out to be a problem when it comes to fighting them. If an implant is colonized by a biofilm, for example, it makes it hard to bring the bacteria under control. As a community, the microorganisms are less vulnerable to various antibiotics. At present, however, it remains to be clarified whether this increased tolerance is due to the limited metabolic activity of dormant cells inside the biofilm, limited diffusion of the antibiotics, or complex communication between bacteria in the biofilm.
Comparison of planktonic form with a biofilm
In his master’s thesis in Professor Knut Drescher’s group at the Biozentrum of the University of Basel, Timon Baltisberger investigated antibiotic tolerance in the model bacterium Vibrio cholerae in greater depth by comparing planktonic bacteria in an agitated liquid medium with those in a biofilm.
To analyze the planktonic bacteria, he first cultured the microorganisms in agitated multi-well plates and monitored their multiplication based on changes in optical density. “I then used seven different antibiotics to investigate how quickly the bacteria were killed off,” Baltisberger says. Given that numerous parallel cultures and dilution series were needed in order to provide statistical confirmation of this data, Baltisberger carried out the pipetting work using a robot that he had also programmed himself as part of his work.
As a result of these analyses using planktonic bacteria, Baltisberger established that, six hours after the antibiotic was administered, six of the seven tested antibiotics had caused over 99% of the bacteria to die off — provided that the dose was above the minimum level.
Biofilms in microfluidic channels
With the biofilms, however, the situation was completely different. Here, bacteria inside the biofilm survived similar quantities of antibiotics for a longer period of time.
For these analyses, Baltisberger cultured the Vibrio bacteria in microfluidic channels, ten of which were arranged on a chip and connected to pumps. This pump system continuously fed culture medium through the channels and could then also be used to administer antibiotic solutions.
“To monitor the effect of these solutions, we positioned the system under a confocal microscope and first measured the signal from a red fluorescent protein produced continuously by the cells. After the antibiotics were administered, we induced production of a different, green fluorescent protein in the Vibrio bacteria, so that only those cells that were still alive were marked,” says Baltisberger, who carried out the work involving biofilm bacteria in collaboration with doctoral students from the Drescher laboratory. “This method offered an elegant way of observing whether — and where in the biofilm — bacteria exhibit certain tolerance to the tested antibiotics.”
“Timon’s master’s thesis has laid the groundwork for how we can study the efficacy of antibiotics in bacterial communities.”
Prof. Knut Drescher, Biozentrum, University of Basel
Higher tolerance
The results confirmed the hypothesis that the center of the biofilm is home to less vulnerable subpopulations of the bacterium that can survive the administration of antibiotics for longer. Theoretically, these Vibrio bacteria can then also recolonize dead regions once antibiotic administration is complete.
“These are not examples of resistance but rather of increased tolerance at the center of the biofilm — and were common to all of the tested antibiotics,” summarizes Baltisberger. “Further investigations are needed to clarify the underlying mechanisms and to develop suitable measures for tackling biofilms.”
A change of plan
Baltisberger really enjoyed working in Knut Drescher’s group and was fascinated not only by the different methods but also by the topical nature of the subject matter.
When he began his studies, however, he would have been surprised to learn that he’d end up doing his master’s thesis in a biophysics laboratory at the Biozentrum. After all, in his time at the cantonal school in Zofingen, he was primarily interested in chemistry. “I was even planning to study chemistry at university,” he recalls.
When he heard about the nanoscience degree at the University of Basel, however, he decided to embark on this interdisciplinary degree course after a series of conversations at the bachelor’s information day. “I particularly liked that the nanoscience degree program was so broad-based and that I didn’t need to commit to a single subject right from the outset,” says Baltisberger, who is originally from the Canton of Aargau. He didn’t regret his choice:
“Coming to Basel to study nanoscience was undoubtedly the right decision.” It’s clear from his choice of subjects during the program that he has a very broad interest in the natural sciences. As well as chemistry, he realized during the block courses as part of the bachelor’s degree that biology and physics were also fascinating fields.
When it came to completing his project work as part of the master’s program, he therefore chose one physical and one biological topic in the teams led by Professors Stefan Willitsch and Daniel Müller before choosing the project in Professor Knut Drescher’s group for his master’s thesis.
“For the next four years, however, I’ll once again be devoting my time to quantum physics,” says Timon Baltisberger with regard to his immediate future. In May 2023, he took up a PhD position in Professor Richard Warburton’s group at the Department of Physics, where he’ll optimize a single-photon source and seek to use it as a source of entangled particles. As in his various previous projects, he is enthusiastic about the topic and confident about the challenges that lie ahead.
We’d like to congratulate Timon on receiving the master’s prize and thank him for his help and support with numerous SNI outreach activities in recent years.