Microorganisms (Jul 2024)

Characterization of <i>Clostridioides difficile</i> Persister Cells and Their Role in Antibiotic Tolerance

  • Osvaldo Inostroza,
  • Juan A. Fuentes,
  • Paulina Yáñez,
  • Giovanni Espinoza,
  • Omar Fica,
  • Camila Queraltó,
  • José Rodríguez,
  • Isidora Flores,
  • Ruth González,
  • Jorge A. Soto,
  • Iván L. Calderón,
  • Fernando Gil

DOI
https://doi.org/10.3390/microorganisms12071394
Journal volume & issue
Vol. 12, no. 7
p. 1394

Abstract

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Clostridioides difficile is a Gram-positive pathogen known for its toxin production and spore formation. It is primarily responsible for most cases of antibiotic-associated diarrhea. Bacterial persisters are a small subset of the population that exhibits transient tolerance to bactericidal substances, and they are of significant medical concern due to their association with the emergence of antibiotic resistance and difficult-to-treat chronic or recurrent infections. Vancomycin, the predominant antibiotic utilized in the management of C. difficile infection, is extensively applied in the realm of clinical practice. Previous studies have demonstrated a persister-like phenotype with treatments involving this antibiotic. However, the mechanism in C. difficile remains largely unknown, primarily due to the challenge of isolating this small population at any given time. To better characterize C. difficile persister cells, we present a study that enables the enrichment and characterization of persister cells from bacterial cultures in both the exponential and stationary phases. Moreover, we could differentiate between triggered (induced using antibiotics such as vancomycin) and spontaneous (stochastic) persister cells. Additionally, we observed the involvement of toxin-antitoxin systems and Clp proteases in persister cell formation.

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