Abstract
Uropathogenic Escherichia coli (UPEC) may undergo a cyclic cascade of morphological alterations that are believed to enhance the potential of UPEC to evade host responses and re-infect host cell. However, knowledge on the pathogenic potential and host activation properties of UPEC during the morphological switch is limited. Microarray analysis was performed on mRNA isolated from human bladder epithelial cells (HBEP) after exposure to three different morphological states of UPEC (normal coliform, filamentous form and reverted form). Cells stimulated with filamentous bacteria showed the lowest number of significant gene alterations, although the number of enriched gene ontology classes was high suggesting diverse effects on many different classes of host genes. The normal coliform was in general superior in stimulating transcriptional activity in HBEP cells compared to the filamentous and reverted form. Top-scored gene entities activated by all three morphological states included IL17C, TNFAIP6, TNF, IL20, CXCL2, CXCL3, IL6 and CXCL8. The number of significantly changed canonical pathways was lower in HBEP cells stimulated with the reverted form (32 pathways), than in cells stimulated with the coliform (83 pathways) or filamentous bacteria (138 pathways). A host cell invasion assay showed that filamentous bacteria were unable to invade bladder cells, and that the number of intracellular bacteria was markedly lower in cells infected with the reverted form compared to the coliform. In conclusion, the morphological state of UPEC has major impact on the host bladder response both when evaluating the number and the identity of altered host genes and pathways.
Highlights
Uropathogenic Escherichia coli (UPEC) may undergo a cyclic cascade of morphological alterations that are believed to enhance the potential of UPEC to evade host responses and re-infect host cell
The filamentous and reverted morphology of UPEC may appear in the urinary tract as a result of the cyclic cascade associated with intracellular invasion and evasion and as a result of antibiotic treatment
In the present study we evaluate changes in gene expression in human primary bladder epithelial cells infected with normal coliform, filamentous and reverted UPEC
Summary
Uropathogenic Escherichia coli (UPEC) may undergo a cyclic cascade of morphological alterations that are believed to enhance the potential of UPEC to evade host responses and re-infect host cell. Uropathogenic Escherichia coli (UPEC) are responsible for the vast majority of UTIs in uncompromised patients and recurrent UTI is often caused by the same clone as the first infection[3,4] This suggests that UPEC have evolved strategies to persist in the urinary tract and evade antibiotic treatment and host response mechanisms. Filamentous E. coli and intracellular colonized bladder epithelial cells have been observed in urine samples from women and children, suggesting that the UPEC cyclic cascade is present in humans[8,11,12]. The filamentous and reverted morphology of UPEC may appear in the urinary tract as a result of the cyclic cascade associated with intracellular invasion and evasion and as a result of antibiotic treatment
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