TY - JOUR

T1 - Cyclic-di-GMP signaling controls metabolic activity in Pseudomonas aeruginosa

AU - Lichtenberg, Mads

AU - Kragh, Kasper Nørskov

AU - Fritz, Blaine

AU - Kirkegaard, Julius B.

AU - Tolker-Nielsen, Tim

AU - Bjarnsholt, Thomas

N1 - Publisher Copyright: Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2022

Y1 - 2022

N2 - Bacteria in biofilms are embedded in extracellular matrix and display low metabolic activity, partly due to insufficient diffusive exchange of metabolic substrate. The extracellular matrix and low metabolic activity both contribute to the high antibiotic tolerance-the hallmark of biofilm bacteria. The second messenger molecule, c-di-GMP, regulates biofilm development in Pseudomonas aeruginosa, where high internal levels lead to biofilm formation and low levels are associated with planktonic bacteria. Using a microcalorimetric approach, we show that c-di-GMP signaling is a major determinant of the metabolic activity of P. aeruginosa, both in planktonic culture and in two biofilm models. The high c-di-GMP content of biofilm bacteria forces them to rapidly spend a large amount of energy on the production of exopolysaccharides, resulting in a subsequent low metabolic state. This suggests that the low metabolic state of bacteria in mature biofilms, to some extent, is a consequence of a c-di-GMP-regulated survival strategy.

AB - Bacteria in biofilms are embedded in extracellular matrix and display low metabolic activity, partly due to insufficient diffusive exchange of metabolic substrate. The extracellular matrix and low metabolic activity both contribute to the high antibiotic tolerance-the hallmark of biofilm bacteria. The second messenger molecule, c-di-GMP, regulates biofilm development in Pseudomonas aeruginosa, where high internal levels lead to biofilm formation and low levels are associated with planktonic bacteria. Using a microcalorimetric approach, we show that c-di-GMP signaling is a major determinant of the metabolic activity of P. aeruginosa, both in planktonic culture and in two biofilm models. The high c-di-GMP content of biofilm bacteria forces them to rapidly spend a large amount of energy on the production of exopolysaccharides, resulting in a subsequent low metabolic state. This suggests that the low metabolic state of bacteria in mature biofilms, to some extent, is a consequence of a c-di-GMP-regulated survival strategy.

KW - biofilm

KW - c-di-GMP

KW - CP: Microbiology

KW - exopolysaccharides

KW - matrix

KW - metabolism

KW - microcalorimetry

KW - Pseudomonas aeruginosa

U2 - 10.1016/j.celrep.2022.111515

DO - 10.1016/j.celrep.2022.111515

M3 - Journal article

C2 - 36260996

AN - SCOPUS:85140415314

VL - 41

SP - 111515

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 3

ER -