PT - JOURNAL ARTICLE AU - Maeve McLaughlin AU - David M. Hershey AU - Leila Reyes Ruiz AU - Aretha Fiebig AU - Sean Crosson TI - A cryptic transcription factor regulates <em>Caulobacter</em> adhesin development AID - 10.1101/2022.05.23.493133 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.05.23.493133 4099 - http://biorxiv.org/content/early/2022/05/23/2022.05.23.493133.short 4100 - http://biorxiv.org/content/early/2022/05/23/2022.05.23.493133.full AB - Alphaproteobacteria commonly produce an adhesin that is anchored to the exterior of the envelope at one cell pole. In Caulobacter crescentus, this adhesin enables permanent attachment to solid surfaces and is known as the holdfast. An ensemble of two-component signal transduction (TCS) proteins control C. crescentus holdfast biogenesis by indirectly regulating expression of HfiA, a potent inhibitor of holdfast synthesis. A genetic selection to discover direct hfiA regulators that function downstream of this adhesion TCS system identified a hypothetical gene that we have named rtrC. Though the primary structure of RtrC bears no resemblance to any defined protein family, RtrC directly binds and regulates dozens of sites on the C. crescentus chromosome via a pseudo-palindromic motif. Among these binding sites is the hfiA promoter, where RtrC functions to directly repress transcription and thereby activate holdfast development. RtrC, the DNA-binding response regulator SpdR, and the transcription factor RtrB together form an OR-gated type I coherent feedforward loop (C1-FFL) that regulates hfiA transcription. C1-FFL motifs are known to buffer gene expression against transient loss of regulating signals, which often occurs in fluctuating natural environments. We conclude that the formerly hypothetical gene, rtrC, encodes a transcription factor that functions downstream of the C. crescentus TCS adhesion control system to regulate development of the holdfast adhesin.Competing Interest StatementThe authors have declared no competing interest.