Molecular mechanism of high force generation by bacterial pili
Final Report Abstract
The question how interbacterial forces control bacterial aggregation and colony dynamics is fundamental to the fields of biophysics and microbiology. The type 4 pilus (T4P) system is a paradigm in which force generation by a complex molecular machine can be studied in a living cell at the single molecule level. Over the years, we have developed the T4P into a tool for controlling interbacterial forces in colonies and early biofilms. We linked T4P-mediated interaction forces between bacteria to structure and dynamics of bacterial colonies. Specifically, we revealed that the activity of extracellular pilus motors enhances local ordering and reduces the fluidity within bacterial colonies. Even a moderate increase in bacterial interaction force triggers a transition from fluidlike to solidlike behavior. Moreover, we correlated bacterial interaction forces and colony fluidity with bacterial fitness. Aggregation into colonies and biofilms can enhance bacterial survivability under antibiotic treatment. We showed that different antibiotics enhance or reduce T4P-mediated attractive forces between neighboring cells in colonies. Even moderate changes in cell-to-cell attraction caused by antibiotics strongly impact on colony fluidity. Vice versa, we revealed that colony fluidity correlates with survivability under antibiotic treatment. In summary, we demonstrated a link between cellular attraction, colony fluidity, and survivability with the potential to optimize the treatment strategy of commonly used drug combinations.
Publications
- (2018) Molecular motors govern liquidlike ordering and fusion dynamics of bacterial colonies, Phys. Rev. Lett., 121, 118102
Welker, A., Cronenberg, T., Zöllner, R., Meel, C., Siewering, K., Bender, N., Hennes, M., Oldewurtel, E.R., Maier, B.
(See online at https://doi.org/10.1103/physrevlett.121.118102) - (2019) Motor properties of PilT- independent type 4 pilus retraction in gonococci, J. Bacteriol., 201(18), e00778
Zöllner, R., Cronenberg, T., Maier, B.
(See online at https://doi.org/10.1128/jb.00778-18) - (2019) Type IV pili: dynamics, biophysics and functional consequences, Nat. Rev. Microbiol. 17(7), 429
Craig, L., Forest, K.T., Maier, B.
(See online at https://doi.org/10.1038/s41579-019-0195-4) - (2019) Type IV pilin post-translational modifications modulate materials properties of bacterial colonies, Biophys. J., 116(5), 938
Zöllner, R., Cronenberg, T., Kouzel, N., Welker, A., Koomey, M., Maier, B.
(See online at https://doi.org/10.1016/j.bpj.2019.01.020) - (2021) Antibiotics modulate attractive interactions in bacterial colonies affecting survivability under combined treatment, PLoS Pathog. 17(2), e1009251
Cronenberg, T., Hennes, M., Wielert, I., Maier, B.
(See online at https://doi.org/10.1371/journal.ppat.1009251) - (2021) How Physical Interactions Shape Bacterial Biofilms, Annu. Rev. Biophys., 50, 401
Maier, B.
(See online at https://doi.org/10.1146/annurev-biophys-062920-063646)