Transcriptional alterations in bladder epithelial cells in response to infection with different morphological states of uropathogenic Escherichia coli

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.

Serine Deamination as a New Acid Resistance Mechanism in Escherichia coli

“…These serine deaminase mutants exhibit increased filamentation. In the context of UTI, filamentous UPEC are deficient in invading bladder cells, forming secondary intracellular bacterial communities, and in establishing quiescent intracellular reservoirs (42, 43). Thus, loss of serine deamination would detrimentally affect E. coli’s ability to form reservoirs in addition to its ability to tolerate low pH.…”

Serine Deamination Is a New Acid Tolerance Mechanism Observed in Uropathogenic Escherichia coli

“…These serine deaminase mutants exhibit increased filamentation. In the context of UTI, filamentous UPEC are deficient in invading bladder cells, forming secondary intracellular bacterial communities, and in establishing quiescent intracellular reservoirs ( 42 , 43 ). Thus, loss of serine deamination could detrimentally affect the ability of UPEC to form reservoirs in addition to its ability to tolerate low pH.…”

Bacterial filamentation during urinary tract infections

“…As daughter cells pinch off from the mother filaments, they divide at faster rates than typically observed for normal E. coli binary fission in standard laboratory growth conditions (e.g., 37˚C in LB) [31,32]. The current understanding is that filaments cannot invade further BECs but must first revert into many rods, which can individually restart the infection cycle by infecting thus far uninfected epithelial cells, making reversal a crucial part of the bacterial morphology cycle during UTIs [33].…”