A genetic switch controls Pseudomonas aeruginosa surface colonization
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A genetic switch controls Pseudomonas aeruginosa surface colonization. / Manner, Christina; Dias Teixeira, Raphael; Saha, Dibya; Kaczmarczyk, Andreas; Zemp, Raphaela; Wyss, Fabian; Jaeger, Tina; Laventie, Benoit Joseph; Boyer, Sebastien; Malone, Jacob G.; Qvortrup, Katrine; Andersen, Jens Bo; Givskov, Michael; Tolker-Nielsen, Tim; Hiller, Sebastian; Drescher, Knut; Jenal, Urs.
In: Nature Microbiology, Vol. 8, 2023, p. 1520–1533.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - A genetic switch controls Pseudomonas aeruginosa surface colonization
AU - Manner, Christina
AU - Dias Teixeira, Raphael
AU - Saha, Dibya
AU - Kaczmarczyk, Andreas
AU - Zemp, Raphaela
AU - Wyss, Fabian
AU - Jaeger, Tina
AU - Laventie, Benoit Joseph
AU - Boyer, Sebastien
AU - Malone, Jacob G.
AU - Qvortrup, Katrine
AU - Andersen, Jens Bo
AU - Givskov, Michael
AU - Tolker-Nielsen, Tim
AU - Hiller, Sebastian
AU - Drescher, Knut
AU - Jenal, Urs
N1 - Publisher Copyright: © 2023, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2023
Y1 - 2023
N2 - Efficient colonization of mucosal surfaces is essential for opportunistic pathogens like Pseudomonas aeruginosa, but how bacteria collectively and individually adapt to optimize adherence, virulence and dispersal is largely unclear. Here we identified a stochastic genetic switch, hecR–hecE, which is expressed bimodally and generates functionally distinct bacterial subpopulations to balance P. aeruginosa growth and dispersal on surfaces. HecE inhibits the phosphodiesterase BifA and stimulates the diguanylate cyclase WspR to increase c-di-GMP second messenger levels and promote surface colonization in a subpopulation of cells; low-level HecE-expressing cells disperse. The fraction of HecE+ cells is tuned by different stress factors and determines the balance between biofilm formation and long-range cell dispersal of surface-grown communities. We also demonstrate that the HecE pathway represents a druggable target to effectively counter P. aeruginosa surface colonization. Exposing such binary states opens up new ways to control mucosal infections by a major human pathogen.
AB - Efficient colonization of mucosal surfaces is essential for opportunistic pathogens like Pseudomonas aeruginosa, but how bacteria collectively and individually adapt to optimize adherence, virulence and dispersal is largely unclear. Here we identified a stochastic genetic switch, hecR–hecE, which is expressed bimodally and generates functionally distinct bacterial subpopulations to balance P. aeruginosa growth and dispersal on surfaces. HecE inhibits the phosphodiesterase BifA and stimulates the diguanylate cyclase WspR to increase c-di-GMP second messenger levels and promote surface colonization in a subpopulation of cells; low-level HecE-expressing cells disperse. The fraction of HecE+ cells is tuned by different stress factors and determines the balance between biofilm formation and long-range cell dispersal of surface-grown communities. We also demonstrate that the HecE pathway represents a druggable target to effectively counter P. aeruginosa surface colonization. Exposing such binary states opens up new ways to control mucosal infections by a major human pathogen.
U2 - 10.1038/s41564-023-01403-0
DO - 10.1038/s41564-023-01403-0
M3 - Journal article
C2 - 37291227
AN - SCOPUS:85161361452
VL - 8
SP - 1520
EP - 1533
JO - Nature Microbiology
JF - Nature Microbiology
SN - 2058-5276
ER -
ID: 357057691