Enteropathogenic<i>Escherichia coli</i>(EPEC) Infection Induces Diarrhea, Intestinal Damage, Metabolic Alterations and Increased Intestinal Permeability in a Murine Model

Ledwaba, Solanka Ellen; Costa, Deiziane Viana da Silva; Bolick, David T.; Giallourou, Natasa; Medeiros, Pedro Hqs; Swann, Jonathan R.; Traore-Hoffman, Afsatou; Potgieter, Natasha; Nataro, James P.; Guerrant, Richard L.

doi:10.1101/2020.06.12.148593

Cited by 3 publications

(2 citation statements)

References 79 publications

(109 reference statements)

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“… 44 , 47 Most recently, we have also published that EPEC can also cause diarrhea and intestinal inflammation in our antibiotic-treated C57Bl/6 mouse model. 55 …”

Section: Roles Of Specific Pathogensmentioning

confidence: 99%

Modeling Enteropathy or Diarrhea with the Top Bacterial and Protozoal Pathogens: Differential Determinants of Outcomes

2021

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Developing effective therapeutics or preventive interventions for important health threats is greatly enhanced whenever accessible models can enable the assessment of clinically important outcomes. While no non-human model is ever perfect, inexpensive in vivo small animal models in such as mice are often of great help in assessing the relevant efficacy of potential interventions. In addition to acute diarrhea, the long-term growth and developmental effects of enteric infections, with or without overt diarrhea, are increasingly recognized. To address these diverse effects, inexpensive animal models are proving to be very helpful. Herein, we review the major clinical concerns with enteric parasitic and bacterial infections that are extremely common worldwide, especially in vulnerable young children living in impoverished areas, and the recently published murine models of these infections and their outcomes. We find that common dietary deficiencies seen in children in developing areas have striking effects on diarrhea and enteropathy outcomes in mice. However, these effects differ with different pathogens. Specifically, the effects of protein or zinc deficiency differ considerably with different major protozoal and bacterial pathogens, suggesting different pathogenetic pathways and intervention effects. The pathogens reviewed are the seven top parasitic and bacterial pathogens seen in children, namely, Cryptosporidium , Giardia , Campylobacter , Shigella , enterotoxigenic Escherichia coli (ETEC), enteroaggregative E. coli (EAEC), and enteropathogenic E. coli (EPEC).

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“… 44 , 47 Most recently, we have also published that EPEC can also cause diarrhea and intestinal inflammation in our antibiotic-treated C57Bl/6 mouse model. 55 …”

Section: Roles Of Specific Pathogensmentioning

confidence: 99%

Modeling Enteropathy or Diarrhea with the Top Bacterial and Protozoal Pathogens: Differential Determinants of Outcomes

2021

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“…This manuscript has been released as a pre-print at bioRxiv 2020.06.12.148593 (Ledwaba et al, 2020).…”

Section: Author's Notementioning

confidence: 99%

Enteropathogenic Escherichia coli Infection Induces Diarrhea, Intestinal Damage, Metabolic Alterations, and Increased Intestinal Permeability in a Murine Model

Ledwaba

Costa

Bolick

et al. 2020

Front. Cell. Infect. Microbiol.

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Enteropathogenic E. coli (EPEC) are recognized as one of the leading bacterial causes of infantile diarrhea worldwide. Weaned C57BL/6 mice pretreated with antibiotics were challenged orally with wild-type EPEC or escN mutant (lacking type 3 secretion system) to determine colonization, inflammatory responses and clinical outcomes during infection. Antibiotic disruption of intestinal microbiota enabled efficient colonization by wild-type EPEC resulting in growth impairment and diarrhea. Increase in inflammatory biomarkers, chemokines, cellular recruitment and pro-inflammatory cytokines were observed in intestinal tissues. Metabolomic changes were also observed in EPEC infected mice with changes in tricarboxylic acid (TCA) cycle intermediates, increased creatine excretion and shifts in gut microbial metabolite levels. In addition, by 7 days after infection, although weights were recovering, EPEC-infected mice had increased intestinal permeability and decreased colonic claudin-1 levels. The escN mutant colonized the mice with no weight loss or increased inflammatory biomarkers, showing the importance of the T3SS in EPEC virulence in this model. In conclusion, a murine infection model treated with antibiotics has been developed to mimic clinical outcomes seen in children with EPEC infection and to examine potential roles of selected virulence traits. This model can help in further understanding mechanisms involved in the pathogenesis of EPEC infections and potential outcomes and thus assist in the development of potential preventive or therapeutic interventions.

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Etiología infecciosa de la diarrea aguda pediátrica, un problema de la Salud Pública

Urbina-Salazar,

Renato Inca-Torres,

Urbina-Salazar

et al. 2023

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La enfermedad diarreica aguda (EDA) es una de las enfermedades con alta mortalidad en pacientes pediátricos se caracteriza por un inicio brusco de signos en el que se destaca diarrea, flatulencias, incluyendo nauseas, emesis, elevación de la temperatura, abdominoalgia entre otras, debido a una infección del aparato gastrointestinal ocasionado por agentes infecciosos patógenos. Esta enfermedad actualmente es uno de los mayores problemas en la salud pública de los países en vías de desarrollo, por su alta repercusión de morbilidad y mortalidad durante la etapa pediátrica, debido a la carencia de ensayos para la detección del agente infeccioso. Se ha reportado que E. coli es uno de los agentes más frecuentes asociada a esta enfermedad, ya que puede encontrarse en varios alimentos contaminados contribuyendo la infección al huésped susceptible. Esta patología al momento es catalogada como autolimitada, considerándose que, en casi la totalidad de los casos será exclusivamente necesario la realización de una historia clínica pediátrica, donde se encuentre todos los acápites necesarios, para posteriormente realizar un examen físico exhaustivo. Es por ello que es necesario abordar más sobre su etiología, mecanismos de transmisión, el manejo y prevención del agente patógeno y principalmente el tratamiento farmacológico de la patología. Palabras clave: E. coli; diarrea; pediatrica; tratamiento médico.

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EnteropathogenicEscherichia coli(EPEC) Infection Induces Diarrhea, Intestinal Damage, Metabolic Alterations and Increased Intestinal Permeability in a Murine Model

Cited by 3 publications

References 79 publications

Modeling Enteropathy or Diarrhea with the Top Bacterial and Protozoal Pathogens: Differential Determinants of Outcomes

Modeling Enteropathy or Diarrhea with the Top Bacterial and Protozoal Pathogens: Differential Determinants of Outcomes

Enteropathogenic Escherichia coli Infection Induces Diarrhea, Intestinal Damage, Metabolic Alterations, and Increased Intestinal Permeability in a Murine Model

Etiología infecciosa de la diarrea aguda pediátrica, un problema de la Salud Pública

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