Abstract
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.
Original language | English |
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Journal | Nature Microbiology |
Volume | 8 |
Pages (from-to) | 1520–1533 |
ISSN | 2058-5276 |
DOIs | |
Publication status | Published - 2023 |
Bibliographical note
Funding Information:We thank F. Hamburger (Biozentrum, University of Basel) for her help with cloning. We thank E. Maffei and A. Harms (Biozentrum, University of Basel) for their support with phage isolation and characterization. This work was supported by a Biozentrum PhD Fellowship to C.M., the Swiss National Science Foundation (grant no. 310030_189253 to U.J.), the NCCR AntiResist funded by Swiss National Science Foundation (grant no. 51NF40_180541 to K.D. and U.J.), the European Research Council (grant no. 716734 to K.D.) and grants from Sygeforsikring Danmark, Danish Innovation Fund and Novoseed to M.G. and T.T.-N.
Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature Limited.