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RelQ-mediated alarmone signalling regulates growth, stress-induced biofilm formation and spore accumulation in Clostridioides difficile .

Areej MalikAdenrele OludiranAsia PoudelOrlando Berumen AlvarezCharles WoodwardErin B Purcell
Published in: Microbiology (Reading, England) (2024)
The bacterial stringent response (SR) is a conserved transcriptional reprogramming pathway mediated by the nucleotide signalling alarmones, (pp)pGpp. The SR has been implicated in antibiotic survival in Clostridioides difficile , a biofilm- and spore-forming pathogen that causes resilient, highly recurrent C. difficile infections. The role of the SR in other processes and the effectors by which it regulates C. difficile physiology are unknown. C. difficile RelQ is a clostridial alarmone synthetase. Deletion of relQ dysregulates C. difficile growth in unstressed conditions, affects susceptibility to antibiotic and oxidative stressors and drastically reduces biofilm formation. While wild-type C. difficile displays increased biofilm formation in the presence of sublethal stress, the Δ relQ strain cannot upregulate biofilm production in response to stress. Deletion of relQ slows spore accumulation in planktonic cultures but accelerates it in biofilms. This work establishes biofilm formation and spore accumulation as alarmone-mediated processes in C. difficile and reveals the importance of RelQ in stress-induced biofilm regulation.
Keyphrases
  • biofilm formation
  • clostridium difficile
  • candida albicans
  • stress induced
  • pseudomonas aeruginosa
  • staphylococcus aureus
  • escherichia coli
  • cystic fibrosis
  • transcription factor
  • wild type
  • gene expression
  • free survival