A genetic switch controls Pseudomonas aeruginosa surface colonization

• Published in: Nature microbiology Vol. 8; no. 8; pp. 1520 - 1533
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2023; Nature Publishing Group
• Subjects: 14/35; 14/63; 38/62; 631/326/41/1969; 631/326/421; 631/326/432; 631/326/46; 631/535/1266; 9/10; 96/31; 96/95; Biofilms; Biomedical and Life Sciences; Cell surface; Colonization; Dispersal; Humans; Infectious Diseases; Life Sciences; Medical Microbiology; Microbiology; Mucosa; Opportunist infection; Parasitology; Pathogens; Pseudomonas aeruginosa; Pseudomonas aeruginosa - metabolism; Stochasticity; Virology; Virulence
• ISSN: 2058-5276; 2058-5276
• DOI: 10.1038/s41564-023-01403-0

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. HecRE is identified as a molecular switch regulating cyclic di-GMP levels and promoting binary cell states during Pseudomonas aeruginosa surface colonization and biofilm development.