XRE transcription factors conserved in Caulobacter and [phi]CbK modulate adhesin development and phage production

• Published in: PLoS genetics 2023-11, Vol.19 (11), p.e1011048
• Main Authors: McLaughlin, Maeve, Fiebig, Aretha, Crosson, Sean
• Format: Article
• Language: English
• Subjects: Adhesion; Analysis; Bacteria; Bacteriophages; Caulobacter; Cell organelles; DNA binding proteins; Genetic aspects; Health aspects; Identification and classification; Infection; Microbiological research; Physiological aspects; Radiation; Transcription factors
• ISSN: 1553-7390
• DOI: 10.1371/journal.pgen.1011048

The xenobiotic response element (XRE) family of transcription factors (TFs), which are commonly encoded by bacteria and bacteriophage, regulate diverse features of bacterial cell physiology and impact phage infection dynamics. Through a pangenome analysis of Caulobacter species isolated from soil and aquatic ecosystems, we uncovered an apparent radiation of a paralogous XRE TF gene cluster, several of which have established functions in the regulation of holdfast adhesin development and biofilm formation in C. crescentus. We further discovered related XRE TFs throughout the class Alphaproteobacteria and its phages, including the [phi]CbK Caulophage, suggesting that members of this cluster impact host-phage interactions. Here we show that a closely related group of XRE transcription factors encoded by both C. crescentus and [phi]CbK can physically interact and function to control the transcription of a common gene set, influencing processes including holdfast development and the production of [phi]CbK virions. The [phi]CbK-encoded XRE paralog, tgrL, is highly expressed at the earliest stages of infection and can directly inhibit transcription of host genes including hfiA, a potent holdfast inhibitor, and gafYZ, an activator of prophage-like gene transfer agents (GTAs). XRE proteins encoded from the C. crescentus chromosome also directly repress gafYZ transcription, revealing a functionally redundant set of host regulators that may protect against spurious production of GTA particles and inadvertent cell lysis. Deleting the C. crescentus XRE transcription factors reduced [phi]CbK burst size, while overexpressing these host genes or [phi]CbK tgrL rescued this burst defect. We conclude that this XRE TF gene cluster, shared by C. crescentus and [phi]CbK, plays an important role in adhesion regulation under phage-free conditions, and influences host-phage dynamics during infection.