XRE Transcription Factors in Caulobacter and fCbK Modulate Adhesion and Phage Viability [ChIP-seq]

During infection, transcriptional changes in both the phage and its host bacterium influence the outcome of infection. The xenobiotic response element (XRE) family of transcription factors (TFs), which are commonly encoded by bacteria and phages, regulate diverse aspects of bacterial cell physiology and can impact phage infection dynamics. Through a pangenome analysis of Caulobacter species isolated from soil and aquatic ecosystems, we uncovered an apparent radiation of an 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 across the class Alphaproteobacteria and its phages, including the fCbK Caulophage, suggesting that members of this gene cluster impact host-phage interactions. Here we show that that a closely related group of XRE proteins, encoded by both C. crescentus and fCbK, can interact to form heteromeric associations and control the transcription of a common gene set, influencing processes such as adhesin development and the progression of fCbK infection. The fCbK XRE paralog, tgrL, is highly expressed at the earliest stages of infection and can directly repress transcription of hfiA, a potent adhesion factor, and gafYZ, a transcriptional activator of prophage-like gene transfer agents (GTAs) encoded on the C. crescentus chromosome. A group of C. crescentus XRE proteins 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 host XRE transcription factors reduced fCbK burst size, while overexpressing these genes or fCbK tgrL rescued this burst defect. We conclude that a large XRE TF gene cluster, shared by C. crescentus and fCbK, plays an important role in adhesion regulation under phage-free conditions, and influences host-phage dynamics during infection. Overall design: Chromatin Immunoprecipitation sequencing (ChIP-seq) for 3xFLAG-tagged XRE transcription factors in Caulobacter crescentus CB15