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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. difficileinfections. 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 ΔrelQ 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.
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The role of extracellular structures in Clostridioides difficile biofilm formation
C. difficile infection (CDI) is a costly and increasing burden on the healthcare systems of many 11 developed countries due to the high rates of nosocomial infections. Despite the availability of 12 several antibiotics with high response rates, effective treatment is hampered by recurrent 13 infections. One potential mechanism for recurrence is the existence of C. difficile biofilms in the 14 gut which persist through the course of antibiotics. In this review, we describe current 15 developments in understanding the molecular mechanisms by which C. difficile biofilms form 16 and are stabilized through extracellular biomolecular interactions.
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- Award ID(s):
- 2310647
- PAR ID:
- 10518125
- Publisher / Repository:
- Elsevier
- Date Published:
- Journal Name:
- Anaerobe
- ISSN:
- 1075-9964
- Page Range / eLocation ID:
- 102873
- Subject(s) / Keyword(s):
- Biofilm, protein-DNA interactions, spores, Clostridioides difficile, type IV pili, flagella, host-pathogen interactions
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1016/j.anaerobe.2024.102873
