New Paper from Dietrich lab shows biofilm anatomy affects susceptibility to drugs

February 01, 2024

Bacteria are traditionally imagined as single-cell organisms, spread out sparsely over surfaces or suspended in liquids, but in many environments the true bacterial mode of growth is in sticky clusters called biofilms. Biofilm formation can be useful to humans—it is integral for example to the production of kombucha tea–but it is more often problematic, because it makes it more difficult to control bacterial growth. Bacteria in biofilms differ biologically from bacteria that grow on their own; they diversify, using specialized metabolic pathways and adjusting their growth rate. These changes help to make the overall population more robust, because metabolic status affects how a bacterium responds to environmental changes or antibiotics. Combined with other features of biofilms, they contribute to the healthcare burden caused by biofilm-based infections worldwide.

Little is known about how bacteria are arranged in biofilms and whether this is relevant to biofilm physiology. A new study published in PLOS Biology from the Dietrich lab, and spearheaded by graduate student Hannah Dayton, has addressed these questions.  It revealed that biofilms formed by an important pathogen, called Pseudomonas aeruginosa, contain bacteria arranged in an ordered pattern and that this arrangement affects their metabolism and drug susceptibility. Using scanning electron microscopy and fluorescence microscopy paired with cell labeling, Dietrich and coworkers found that P. aeruginosa cells in biofilms are packed lengthwise and arranged perpendicularly to their growth substrate. They also found that mutations that modify the cell surface disrupt this arrangement. When they tested the effects of a sugar or an antibiotic added from the outside to a fully formed biofilm, they observed that a disordered cellular arrangement enhanced the responsiveness of cells in biofilm subzones. Collaborating with the research groups of Wei Min (Columbia Chemistry), Raju Tomer (Columbia Biological Sciences), Jasmine Nirody (University of Chicago), and Anu Janakiraman (CUNY) they showed that biofilm anatomy influences the location of peak metabolic activity within biofilms and affects the distribution of substrate. Together, these observations indicate that biofilm microstructure is a property that can be tuned to influence the metabolism of resident subpopulations and affect the overall survival of the group. They have implications for our approaches to treating infections caused by P. aeruginosa and other biofilm-forming pathogens.