Abstract
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 neighboring 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 behavior, which is subject to selection pressure in clinical environments.
Original language | English |
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Journal | Cell Host & Microbe |
Volume | In Press |
DOIs | |
Publication status | E-pub ahead of print - 23 Jan 2025 |
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Supporting data for "The genus Serratia revisited by genomics"
Williams, D. (Creator), Grimont, P. A. D. (Creator), Cazares, A. (Creator), Grimont, F. (Creator), Ageron, E. (Creator), A. Pettigrew, K. (Creator), Cazares, D. (Creator), Njamkepo, E. (Creator), Weill, F.-X. (Creator), Heinz, E. (Creator), T. G Holden, M. (Creator), Thomson, N. R. (Creator) & J. Coulthurst, S. (Creator), Figshare, 2022
DOI: 10.6084/m9.figshare.18051824.v2
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