Interaction dynamics of bacterial biofilms with bacteriophages


Biofilms are antibiotic-tolerant, sessile bacterial communities that occupy most moist surfaces on Earth and represent a major mode of bacterial life. Another common feature of bacterial life is exposure to viral parasites (termed phages), which are a dominant force in bacterial population control throughout nature. Little is known about the interactions between biofilm-dwelling bacteria and phages. This project is designed to fill this gap using a combination of novel methodology, experimental systems, and mathematical modeling. By genetically manipulating bacterial hosts and their phages, and by varying environmental conditions, we are investigating the fundamental biological and physical determinants of phage spread within biofilm communities. In addition, this project investigates how biofilms respond to phage attack, focusing in particular on proximate response mechanisms and the population dynamics of phage-resistant and phage-susceptible cells as a function of biofilm spatial structure. This project is uncovering the major mechanistic and evolutionary elements of biofilm-phage interactions. This project greatly enriches our knowledge of microbial ecology and will motivate novel strategies for bacterial biofilm control, an increasingly urgent priority in light of widespread antibiotic ineffectiveness.


  • Clarifying the biological, environmental, and physical determinants of phage spread: tool development and foundational work.
  • Biofilm response to phage infection on the intra-generational and evolutionary time scales.
  • Using species-specific phages to modify the composition and phenotypic properties of multi-species biofilms.

Project results


Multispecies phase diagram of biofilm architectures reveals biophysical principles of biofilm development
H. Jeckel*, F. Diaz-Pascual*, D.J. Skinner*, B. Song*, E. Jimenez Siebert, K. Strenger, E. Jelli, S. Vaidya, J. Dunkel, K. Drescher
PLOS Biology, in press (2022). (* equal contribution) [bioRxiv] [journal link]

Vibrio cholerae biofilm dispersal regulator causes cell release from matrix through type IV pilus retraction
P.K. Singh*, D.K.H. Rode*, P. Buffard, K. Nosho, M. Bayer, H. Jeckel, E. Jelli, K. Neuhaus, E. Jiménez-Siebert, N. Peschek, T. Glatter, K. Papenfort, K. Drescher
submitted (2021). (* equal contribution) [bioRxiv] [journal link]

Journal articles

Interkingdom assemblages in human saliva display group-level surface mobility and disease-promoting emergent functions
Z. Ren*, H. Jeckel*, A. Simon-Soro, Z. Xiang, Y. Liu, I.M. Cavalcanti, J. Xiao, N.-N. Tin, A. Hara, K. Drescher#, H. Koo#
PNAS 119, e2209699119 (2022). (* equal contribution) [journal link]

VxrB influences antagonism within biofilms by controlling competition through extracellular matrix production and type 6 secretion
J.K. Teschler, E. Jiménez-Siebert, H. Jeckel, P.K. Singh, J.H. Park, S. Pukatzki, C.D. Nadell, K. Drescher, F.H. Yildiz
mBio, 13:e01885-22 (2022). [journal link]

Spatial alanine metabolism determines local growth dynamics of Escherichia coli colonies
F. Díaz-Pascual, M. Lempp, K. Nosho, H. Jeckel, J.K. Jo, K. Neuhaus, R. Hartmann, E. Jelli, M.F. Hansen, A. Price-Whelan, L.E.P. Dietrich, H. Link, K. Drescher
eLife, 10:e70794 (2021). [journal link] [bioRxiv]

Matrix-trapped viruses can prevent invasion of bacterial biofilms by colonizing cells
M.C. Bond, L. Vidakovic, P.K. Singh, K. Drescher, C.D. Nadell
eLife, 10:e65355 (2021). [journal link]

Single-objective high-resolution confocal light sheet fluorescence microscopy for standard biological sample geometries
S. Yordanov, K. Neuhaus, R. Hartmann, F. Díaz-Pascual, L. Vidakovic, P.K. Singh, K. Drescher
Biomedical Optics Express 12, 3372-3391 (2021). [journal link]

Quantitative image analysis of microbial communities with BiofilmQ
R. Hartmann*, H. Jeckel*, E. Jelli*, P.K. Singh, S. Vaidya, M. Bayer, D. Rode, L. Vidakovic, F. Díaz-Pascual, J.C.N. Fong, A. Dragoš, O. Besharova, J.G. Thöming, N. Netter, S. Häussler, C.D. Nadell, V. Sourjik, A.T. Kovács, F.H. Yildiz, K. Drescher
Nature Microbiology 6, 151-156 (2021). (* equal contribution) [journal link]
       -- download/use the BiofilmQ software tool, view video tutorials.
       -- see perspective by Divya Choudhary and Chloé J. Cassaro in Nature Rev. Microbiol.

Advances and opportunities in image analysis of bacterial cells and communities
H. Jeckel, K. Drescher
FEMS Microbiology Reviews, fuaa062 (2021). [journal link]

Topological metric detects hidden order in disordered media
D.J. Skinner, B. Song, H. Jeckel, E. Jelli, K. Drescher, J. Dunkel
Physical Review Letters 126, 048101 (2021). [journal link]
       -- see viewpoint by Suraj Shankar in Physics.

Vibrio cholerae biofilm scaffolding protein RbmA shows an intrinsic, phosphate‐dependent autoproteolysis activity
M. Maestre‐Reyna, W.‐C. Huang, W.‐J. Wu, P.K. Singh, R. Hartmann, P.‐H. Wang, C.‐C. Lee, T. Hikima, M. Yamamoto, Y. Bessho, K. Drescher, M.‐D. Tsai, A.H.‐J. Wang
IUBMB Life 73, 418-431 (2021). [journal link]

RNA-mediated control of cell shape modulates antibiotic resistance in Vibrio cholerae
R. Herzog, N. Peschek, P.K. Singh, M. Sprenger, F. Meyer, K.S. Fröhlich, L. Schröger, M. Bramkamp, K. Drescher, K. Papenfort
Nature Communications 11, 6067 (2020). [journal link]

Multicellular and unicellular responses of microbial biofilms to stress
D.K.H. Rode*, P.K. Singh*, K. Drescher
Biological Chemistry 401, 1365–1374 (2020). (* equal contribution) [journal link]

BacStalk: a comprehensive and interactive image analysis software tool for bacterial cell biology
R. Hartmann*, M.C.F. van Teeseling*, M. Thanbichler, K. Drescher
Molecular Microbiology 114, 140-150 (2020). (* equal contribution) [journal link]
       -- download/use the BacStalk software tool, view video tutorials.

Privatization of biofilm matrix in structurally heterogeneous biofilms
S.B. Otto, M. Martin, D. Schäfer, R. Hartmann, K. Drescher, S. Brix, A. Dragoš, A.T. Kovács
mSystems 5, e00425-20 (2020). [journal link]

A tyrosine phosphoregulatory system controls exopolysaccharide biosynthesis and biofilm formation in Vibrio cholerae
C. Schwechheimer, K. Hebert, S. Tripathi, P.K. Singh, K.A. Floyd, E.R. Brown, M.E. Porcella, J. Osorio, J.T.M. Kiblen, F.A. Pagliai, K.Drescher, S.M. Rubin, F.H. Yildiz
PLOS Pathogens 16, e1008745 (2020). [journal link]

Upregulation of virulence genes promotes Vibrio cholerae biofilm hyperinfectivity
A.L. Gallego-Hernandez, W.H. DePas, J.H. Park, J.K. Teschler, R. Hartmann, H. Jeckel, K. Drescher, S. Beyhan, D.K. Newman, F.H. Yildiz
PNAS 117, 11010–11017 (2020). [journal link]

Biofilm structure promotes coexistence of phage-resistant and phage-susceptible bacteria
E.L. Simmons, M.C. Bond, B. Koskella, K. Drescher, V. Bucci, C.D. Nadell
mSphere 5, e00877-19 (2020). [bioRxiv] [journal link]

Breakdown of Vibrio cholerae biofilm architecture induced by antibiotics disrupts community barrier function
F. Diaz-Pascual, R. Hartmann, M. Lempp, L. Vidakovic, B. Song, H. Jeckel, K.M. Thormann, F.H. Yildiz, J. Dunkel, H. Link, C.D. Nadell, K. Drescher
Nature Microbiology 4, 2136-2145 (2019). [Free Access] [journal link]
       -- see perspective by Divya Choudhary and Chloé J. Cassaro in Nature Rev. Microbiol.

Flow-induced symmetry breaking in growing bacterial biofilms
P. Pearce, B. Song, D.J. Skinner, R. Mok, R. Hartmann, P.K. Singh, H. Jeckel, J.S. Oishi, K. Drescher, J. Dunkel
Physical Review Letters 123, 258101 (2019). [journal link] [bioRxiv]

Learning the space-time phase diagram of bacterial swarm expansion
H. Jeckel, E. Jelli, R. Hartmann, P.K. Singh, R. Mok, J.F. Totz, L. Vidakovic, B. Eckhardt, J. Dunkel, K. Drescher
PNAS 116, 1489-1494 (2019). [Open Access] [dataset explorer]
       -- Youtube video summary.

Emergence of three-dimensional order and structure in growing biofilms
R. Hartmann, P.K. Singh*, P. Pearce*, R. Mok*, B. Song, F. Diaz-Pascual, J. Dunkel, K. Drescher
Nature Physics 15, 251-256 (2019). (* equal contribution) [journal link] [Europe PMC] [data repository]
       -- see Jordi Garcia-Ojalvo's Perspective in Nature Physics.
       -- see Phil Pearce's "Behind the paper" story.

Selective enrichment of slow-growing bacteria in a metabolism-wide CRISPRi library with a TIMER protein
D. Beuter, J. Gomes-Filho, L. Randau, F. Díaz-Pascual, K. Drescher, H. Link
ACS Synthetic Biology 7, 2775-2782 (2018). [journal link]

Division of labor during biofilm matrix production
A. Dragos, H.T. Kiesewalter, M. Martin, C.-Y. Hsu, R. Hartmann, T. Wechsler, K. Drescher, N. Stanley-Wall, R. Kümmerli, A.T. Kovacs
Current Biology 28, 1-11 (2018). [journal link]
       -- see highlight in Nature Rev. Microbiol. by A. York [link]
       -- see highlight in Current Biology by B. Momeni [link]
       -- see "Behind the Paper" story [link]

Cell adhesion and fluid flow jointly initiate biofilm genetic structure
R. Martinez-Garcia, C.D. Nadell, R. Hartmann, K. Drescher, J.A. Bonachela
PLoS Computational Biology 14, e1006094 (2018). [Open Access]

Dynamic biofilm architecture confers individual and collective mechanisms of viral protection
L. Vidakovic, P.K. Singh, R. Hartmann, C.D. Nadell, K. Drescher
Nature Microbiology 3, 26-31 (2018). [Free Access] [journal link] [Europe PMC]
       -- see perspective by J. Price & M.R. Chapman in Nature Microbiol. [link]

Phage mobility is a core determinant of phage-bacteria coexistence in biofilms
M. Simmons, K. Drescher, C.D. Nadell, V. Bucci
ISME Journal 12, 531-543 (2018). [Open Access]

Vibrio cholerae combines individual and collective sensing to trigger biofilm dispersal
P.K. Singh, S. Bartalomej, R. Hartmann, H. Jeckel, L. Vidakovic, C.D. Nadell, K. Drescher
Current Biology 27, 1-8 (2017). [Open Access]
       -- see F1000 recommendation by Chris Waters


  • Funded by: European Research Council