Sponge RNA controlled quorum sensing transition in Vibrio cholerae

• Applicant: Professor Dr. Kai Papenfort
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms ; Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology ; Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2015 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 285804960

• Final Report Year: 2024

Final Report Abstract

Quorum sensing (QS) is a critical mechanism for coordinating behaviors in many microorganisms. In Vibrio cholerae, a significant human pathogen and model organism for studying microbial communication, QS is essential for collective behaviors like biofilm formation and virulence. To perform QS effectively, V. cholerae must detect, interpret, and integrate extracellular chemical signals (autoinducers) and convert them into gene expression changes. This process involves a network of transcriptional regulators and small regulatory RNAs (sRNAs) that work together to ensure optimal QS function. This project focused on investigating a newly identified component of this network, called QrrX. QrrX is part of a less understood group of sponge RNAs - non-coding regulators that specifically counteract other non-coding regulators. Our results revealed that QrrX base-pairs with and inhibits the activity of Qrr1-4 sRNAs, which are the main regulatory elements of the QS pathway in V. cholerae. Notably, we observed that cells lacking qrrX are impaired to transition accurately from low to high cell density, suggesting that QrrX influences gene expression on a broad scale. Additionally, we have identified a novel transcriptional regulator (QrrT) that drives qrrX expression. Together, we believe this research significantly advanced our understanding of the QS pathway in V. cholerae and provided insights into the broader architecture of QS networks and the role of sponge RNAs within them.

Publications

• Regulation outside the box: New mechanisms for small RNAs. Molecular Microbiology, 114(3), 363-366.
  Fröhlich, Kathrin S. & Papenfort, Kai
  
• An RNA sponge controls quorum sensing dynamics and biofilm formation in Vibrio cholerae. Nature Communications, 13(1).
  Huber, Michaela; Lippegaus, Anne; Melamed, Sahar; Siemers, Malte; Wucher, Benjamin R.; Hoyos, Mona; Nadell, Carey; Storz, Gisela & Papenfort, Kai
  
• Microbial Communication via Pyrazine Signaling: A New Class of Signaling Molecules Identified in Vibrio cholerae. Israel Journal of Chemistry, 63(5-6).
  Silpe, Justin E.; Duddy, Olivia P. & Papenfort, Kai
  
• Small regulatory RNAs in Vibrio cholerae. microLife, 4.
  Ghandour, Rabea & Papenfort, Kai
  
• Small RNAs, Large Networks: Posttranscriptional Regulons in Gram-Negative Bacteria. Annual Review of Microbiology, 77(1), 23-43.
  Papenfort, Kai & Melamed, Sahar