Competitive behaviors in Serratia marcescens are coordinately regulated by a lifestyle switch frequently inactivated in the clinical environment

TY - JOUR

T1 - Competitive behaviors in Serratia marcescens are coordinately regulated by a lifestyle switch frequently inactivated in the clinical environment

AU - Williams, David

AU - Hawkins, Alexandra

AU - Hernandez, Ruth

AU - Mariano, Giuseppina

AU - Mathers, Katharine

AU - Buchanan, Grant

AU - Stonier, Barnaby

AU - Inkster, Teresa

AU - Leanord, Alistair

AU - Chalmers, James

AU - Thomson, Nicholas R.

AU - Holden, Matthew

AU - Coulthurst, Sarah

N1 - Publisher Copyright: © 2025 The Authors

PY - 2025/2/12

Y1 - 2025/2/12

N2 - Opportunistic bacterial pathogens must compete with other bacteria and switch between host and environment-adapted states. Type VI secretion systems (T6SSs) occur widely in Gram-negative bacteria and can efficiently kill neighbouring competitors. We determined the distribution of T6SSs across the genus Serratia and observed that a highly-conserved antibacterial T6SS is differentially-active between closely-related clinical isolates of Serratia marcescens. By combining genomic and experimental approaches, we identified a genus-core two-component system, BetR-Reg1-Reg2, that controls T6SS activity and exhibits frequent inactivating mutations, exclusively in S. marcescens isolates of clinical origin. This regulatory system controls a number of lifestyle-related traits at transcriptional and post-translational levels, including T6SS activity, antibiotic production, motility and adhesion, with loss of BetR increasing virulence in an in vivo infection model. Our data support a model whereby this system represents a conserved, modular switch from sessile to pioneering and aggressive behaviour, which is subject to selection pressure in clinical environments.

AB - Opportunistic bacterial pathogens must compete with other bacteria and switch between host and environment-adapted states. Type VI secretion systems (T6SSs) occur widely in Gram-negative bacteria and can efficiently kill neighbouring competitors. We determined the distribution of T6SSs across the genus Serratia and observed that a highly-conserved antibacterial T6SS is differentially-active between closely-related clinical isolates of Serratia marcescens. By combining genomic and experimental approaches, we identified a genus-core two-component system, BetR-Reg1-Reg2, that controls T6SS activity and exhibits frequent inactivating mutations, exclusively in S. marcescens isolates of clinical origin. This regulatory system controls a number of lifestyle-related traits at transcriptional and post-translational levels, including T6SS activity, antibiotic production, motility and adhesion, with loss of BetR increasing virulence in an in vivo infection model. Our data support a model whereby this system represents a conserved, modular switch from sessile to pioneering and aggressive behaviour, which is subject to selection pressure in clinical environments.

KW - Serratia marcescens

KW - bacterial genomics and evolution

KW - clinical adaptation

KW - inter-bacterial competition

KW - opportunistic bacterial pathogens

KW - type VI secretion system

UR - https://www.scopus.com/pages/publications/85217100157

U2 - 10.1016/j.chom.2025.01.001

DO - 10.1016/j.chom.2025.01.001

M3 - Article

C2 - 39884275

SN - 1931-3128

VL - 33

SP - 252

EP - 266

JO - Cell Host & Microbe

JF - Cell Host & Microbe

IS - 2

M1 - e5

ER -