Enteroaggregative Escherichia coli (EAEC) impairs growth while malnutrition worsens EAEC infection: a novel murine model of the infection malnutrition cycle.
BACKGROUND
Enteroaggregative Escherichia coli is emerging as an increasingly recognized cause of persistent, mildly inflammatory diarrhea in the United States, especially among patients with AIDS, as well as among children, for whom it is accompanied by growth shortfalls.


METHODS
We describe a novel model of disease induced in neonatal and weaned C57BL/6 mice by pathogenic strains of enteroaggregative E. coli 042 and JM221.


RESULTS
Enteroaggregative E. coli caused growth impairment (up to 47%), persistent stool shedding (for >3 weeks), and a substantial tissue burden of organisms (150,000 organisms per milligram of tissue), as well as histopathological changes in the colonic epithelium (days 4 and 6 of infection) using the model. Undernutrition in neonatal mice, as well as in weaned mice, intensified infection by 1-4 logs, as assessed by quantitative polymerase chain reaction for fecal shedding of organisms. Growth impairment was dependent on both microorganism burden and challenge dose.


CONCLUSIONS
Both neonatal and weaned mice provide models for a vicious cycle of enteroaggregative E. coli infection that causes growth shortfalls and undernutrition, thus worsening infection. Hence, these neonatal and weaned mice provide the opportunity to dissect mechanisms of this cycle in childhood malnutrition, as well as to define the role played by innate and acquired host defenses in this important infection.
Roche
James K
JK
Center for Global Health, Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
Cabel
Ace
A
Sevilleja
Jesus
J
Nataro
James
J
Guerrant
Richard L
RL
D000818:Animals; D000831:Animals, Newborn; D003106:Colon / Q000382:microbiology / Q000473:pathology; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000150:complications* / Q000382:microbiology / Q000473:pathology*; D005243:Feces / Q000382:microbiology; D005260:Female; D006130:Growth Disorders / Q000209:etiology; D006651:Histocytochemistry; D006801:Humans; D044342:Malnutrition / Q000150:complications* / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008853:Microscopy; D014886:Weaning