Control, patterns, and resistance in bacterial populations

Time-lapse fluorescence images of a bacterial colony developing metabolic layering (13.4–14.7 h) — Time-lapse of a diffusion-limited bacterial colony developing metabolic layering, driven by an engineered feedback circuit (Bittihn, Didovyk, Tsimring, Hasty, Nat. Microbiol. 2020).

Bacteria coordinate through chemical signals, physical forces, and metabolic gradients, giving rise to collective behavior far richer than that of a single cell. Combining synthetic biology with quantitative modeling, we study these phenomena to uncover physical principles and to point toward new control strategies.

We showed that an engineered quorum-sensing circuit undergoes a Hopf bifurcation into sustained population oscillations that can stabilize otherwise competing strains, and that metabolic gradients in diffusion-limited colonies drive characteristic growth oscillations. The same metabolic layering strongly shapes antibiotic resistance — a mechanism we study together with the Schultz lab (Dartmouth).

Complementary work develops stochastic theory for evolutionary dynamics in growing populations, from the suppression of beneficial mutations to gene conversion on rugged fitness landscapes.

Selected publications

Dynamical model of antibiotic responses linking expression of resistance to metabolism explains emergence of heterogeneity during drug exposures

M. Stevanovic, J. P. Teuber Carvalho, P. Bittihn, D. Schultz

Physical Biology 21, 036002 (2024)

DOI

Nutrient gradients mediate complex colony-level antibiotic responses in structured microbial populations

M. Stevanovic, T. Boukéké-Lesplulier, L. Hupe, J. Hasty, P. Bittihn, D. Schultz

Frontiers in Microbiology 13 (2022)

Genetically engineered control of phenotypic structure in microbial colonies

P. Bittihn, A. Didovyk, L. S. Tsimring, J. Hasty

Nature Microbiology 5, 697 (2020)

DOI

Divergent aging of isogenic yeast cells revealed through single-cell phenotypic dynamics

M. Jin, Y. Li, R. O'Laughlin, P. Bittihn, L. Pillus, L. S. Tsimring, J. Hasty, N. Hao

Cell Systems 8, 242 (2019)

DOI

Rational engineering of synthetic microbial systems: From single cells to consortia

P. Bittihn, M. O. Din, L. S. Tsimring, J. Hasty

Current Opinion in Microbiology 45, 92 (2018)

DOI

Gene conversion facilitates adaptation on rugged fitness landscapes

P. Bittihn, L. S. Tsimring

Genetics 207, 1577 (2017)

DOI

Suppression of beneficial mutations in dynamic microbial populations

P. Bittihn, J. Hasty, L. S. Tsimring

Physical Review Letters 118, 028102 (2017)

Multi-generational silencing dynamics control cell aging

Y. Li, M. Jin, R. O'Laughlin, P. Bittihn, L. S. Tsimring, L. Pillus, J. Hasty, N. Hao

PNAS 114, 11253 (2017)

DOI

A stabilized microbial ecosystem of self-limiting bacteria using synthetic quorum-regulated lysis

S. R. Scott, M. O. Din, P. Bittihn, L. Xiong, L. S. Tsimring, J. Hasty

Nature Microbiology 2, 17083 (2017)