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Evaluación de la fagoterapia frente a infecciones producidas por Klebsiella pneumoniae productora de carbapenemasas en un modelo de Galleria mellonella

Authors: Alcantara Lozano, Gabriela Ivett; Quispe Villegas, Gustavo Alonso;

Evaluación de la fagoterapia frente a infecciones producidas por Klebsiella pneumoniae productora de carbapenemasas en un modelo de Galleria mellonella

Abstract

Antecedente: La emergencia de Klebsiella pneumoniae productoras de carbapenemasas y la reducción de alternativas terapéuticas constituye un serio problema de salud pública. Debido a ello, la fagoterapia resulta una alternativa para ser evaluada frente a la amenaza de la multidrogorresistencia del patógeno. Objetivo: Evaluar la actividad terapéutica de bacteriófagos de Klebsiella pneumoniae productoras de carbapenemasas, empleando como modelo in vivo larvas de Galleria mellonella aplicando una terapia de rescate de bacteriófagos líticos obtenidos a partir de aguas servidas, en un hospital público de nivel III. Materiales y Métodos: se realizó un estudio experimental. Se aisló un bacteriófago denominado GA23 de aguas residuales hospitalarias y se determinó su capacidad lítica frente a cepas de Klebsiella pneumoniae de origen clínico. La optimización de la multiplicidad de infección permitió elaborar ensayos de supervivencia con el modelo de Galleria mellonella; evaluada mediante una curva de Kaplan-Meier. Resultados: De la totalidad de cepas bacterianas evaluadas, sólo la C25 permitió generar bacteriófagos líticos (1/12, 8.3%); en la curva de un solo paso, la fase exponencial corresponde a 30 minutos, y el tamaño de explosión a 164 PFU/bacteria. El 100% de larvas sobrevivieron al inóculo conjunto del fago GA23 y la cepa C25 a las 96 horas. Conclusiones: El fago GA23 en el modelo de Galleria mellonella carece de actividad lítica in vitro hacia Klebsiella pneumoniae productora de carbapenemasas, pero prolonga la sobrevida frente a la infección por Klebsiella pneumoniae C25.

Background: The emergence of carbapenemase-producing Klebsiella pneumoniae and the drastic decrease of therapeutic alternatives to treat them constitutes a significant public health challenge. Consequently, phage therapy stands out as a potential alternative to be evaluated against the threat of multidrug resistance of this pathogen. Objective: To assess the therapeutic activity of bacteriophages targeting carbapenemase-producing Klebsiella pneumoniae, using Galleria mellonella larvae as an in vivo model and applying a rescue therapy with lytic bacteriophages obtained from hospital wastewater in a level III public hospital. Materials and Methods: An experimental study was conducted. A bacteriophage named GA23 was isolated from hospital wastewater, and its lytic capacity against clinical strains of Klebsiella pneumoniae was determined. Optimization of the multiplicity of infection allowed for survival assays using the Galleria mellonella model, assessed through a Kaplan-Meier curve. Results: Among all strains, only strain C25 allowed the generation of lytic bacteriophages (1/12, 8.3%); the exponential phase corresponds to 30 minutes, and the burst size to 164 PFU/bacteria. Up to 100% of larvae survived the combined inoculum of the GA23 phage and the C25 strain at 96 hours. Conclusions: In the Galleria mellonella model, phage GA23 lacks in vitro lytic activity against carbapenemase-producing Klebsiella pneumoniae but extends survival against Klebsiella pneumoniae C25 infection.

Country
Peru
Keywords

Klebsiella pneumoniae, Galleria mellonella, Bacteriófagos, http://purl.org/pe-repo/ocde/ford#3.03.08, http://purl.org/pe-repo/ocde/ford#1.06.01, http://purl.org/pe-repo/ocde/ford#1.06.03, Carbapenemase-Producing Enterobacteriaceae

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
0
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