Mutual enhancement of virulence by enterotoxigenic and enteropathogenic Escherichia coli.
Enterotoxigenic Escherichia coli (ETEC) and enteropathogenic E. coli (EPEC) are common causes of diarrhea in children in developing countries. Dual infections with both pathogens have been noted fairly frequently in studies of diarrhea around the world. In previous laboratory work, we noted that cholera toxin and forskolin markedly potentiated EPEC-induced ATP release from the host cell, and this potentiated release was found to be mediated by the cystic fibrosis transmembrane conductance regulator. In this study, we examined whether the ETEC heat-labile toxin (LT) or the heat-stable toxin (STa, also known as ST) potentiated EPEC-induced ATP release. We found that crude ETEC culture filtrates, as well as purified ETEC toxins, did potentiate EPEC-induced ATP release in cultured T84 cells. Coinfection of T84 cells with live ETEC plus EPEC bacteria also resulted in enhanced ATP release compared to EPEC alone. In Ussing chamber studies of chloride secretion, adenine nucleotides released from the host by EPEC also significantly enhanced the chloride secretory responses that were triggered by crude ETEC filtrates, purified STa, and the peptide hormone guanylin. In addition, adenosine and LT had additive or synergistic effects in inducing vacuole formation in T84 cells. Therefore, ETEC toxins and EPEC-induced damage to the host cell both enhance the virulence of the other type of E. coli. Our in vitro data demonstrate a molecular basis for a microbial interaction, which could result in increased severity of disease in vivo in individuals who are coinfected with ETEC and EPEC.
Department of Medicine, Division of Infectious Diseases, Room 317, Biomedical Research Bldg., 3435 Main St., Buffalo, NY 14214, USA. jcrane@buffalo.edu
John K
JK
Crane
Shilpa S
SS
Choudhari
Tonniele M
TM
Naeher
Michael E
ME
Duffey
D000255:Adenosine Triphosphate / Q000378:metabolism; D001427:Bacterial Toxins / Q000378:metabolism*; D002460:Cell Line; D004768:Enterotoxins / Q000276:immunology* / Q000378:metabolism; D004926:Escherichia coli / Q000276:immunology / Q000472:pathogenicity*; D004927:Escherichia coli Infections / Q000503:physiopathology*; D029968:Escherichia coli Proteins; D014774:Virulence / Q000502:physiology*
D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; C034151:heat stable toxin (E coli); D000255:Adenosine Triphosphate