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Correlating Antibiotic-Induced Dysbiosis to Clostridioides difficile Spore Germination and Host Susceptibility to Infection Using an Ex Vivo Assay.
Moore, John H; Salahi, Armita; Honrado, Carlos; Warburton, Christopher; Tate, Steven; Warren, Cirle A; Swami, Nathan S.
Afiliación
  • Moore JH; Electrical and Computer Engineering, University of Virginia, Charlottesville, Virginia 22904, United States.
  • Salahi A; Electrical and Computer Engineering, University of Virginia, Charlottesville, Virginia 22904, United States.
  • Honrado C; Electrical and Computer Engineering, University of Virginia, Charlottesville, Virginia 22904, United States.
  • Warburton C; Electrical and Computer Engineering, University of Virginia, Charlottesville, Virginia 22904, United States.
  • Tate S; Electrical and Computer Engineering, University of Virginia, Charlottesville, Virginia 22904, United States.
  • Warren CA; Infectious Diseases, School of Medicine, University of Virginia, Charlottesville, Virginia 22903, United States.
  • Swami NS; Electrical and Computer Engineering, University of Virginia, Charlottesville, Virginia 22904, United States.
ACS Infect Dis ; 9(10): 1878-1888, 2023 10 13.
Article en En | MEDLINE | ID: mdl-37756389
Antibiotic-induced microbiota disruption and its persistence create conditions for dysbiosis and colonization by opportunistic pathogens, such as those causing Clostridioides difficile (C. difficile) infection (CDI), which is the most severe hospital-acquired intestinal infection. Given the wide differences in microbiota across hosts and in their recovery after antibiotic treatments, there is a need for assays to assess the influence of dysbiosis and its recovery dynamics on the susceptibility of the host to CDI. Germination of C. difficile spores is a key virulence trait for the onset of CDI, which is influenced by the level of primary vs secondary bile acids in the intestinal milieu that is regulated by the microbiota composition. Herein, the germination of C. difficile spores in fecal supernatant from mice that are subject to varying degrees of antibiotic treatment is utilized as an ex vivo assay to predict intestinal dysbiosis in the host based on their susceptibility to CDI, as determined by in vivo CDI metrics in the same mouse model. Quantification of spore germination down to lower detection limits than the colony-forming assay is achieved by using impedance cytometry to count single vegetative bacteria that are identified based on their characteristic electrical physiology for distinction vs aggregated spores and cell debris in the media. As a result, germination can be quantified at earlier time points and with fewer spores for correlation to CDI outcomes. This sets the groundwork for a point-of-care tool to gauge the susceptibility of human microbiota to CDI after antibiotic treatments.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Clostridioides difficile / Infecciones por Clostridium Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: ACS Infect Dis Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Clostridioides difficile / Infecciones por Clostridium Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: ACS Infect Dis Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos