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

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Katarina Persson ◽  
Ulrika Petersson ◽  
Charlotte Johansson ◽  
Isak Demirel ◽  
Robert Kruse
Keyword(s):  
Escherichia Coli ◽  
Epithelial Cells ◽  
Host Cell ◽  
Host Responses ◽  
Filamentous Bacteria ◽  
Pathogenic Potential ◽  
Filamentous Form ◽  
Morphological Alterations ◽  
Host Genes ◽  
In Cells

AbstractUropathogenic 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.

Interactions Between Salmonella Typhimurium, Enteropathogenic Escherichia Coli (EPEC), and Host Epithelial Cells

1995 ◽  
Vol 9 (1) ◽  
pp. 31-36 ◽  
Author(s):  
B.B. Finlay
Keyword(s):  
Escherichia Coli ◽  
Epithelial Cells ◽  
Salmonella Typhimurium ◽  
Host Cell ◽  
Inositol Phosphate ◽  
Enteric Pathogens ◽  
Host Protein ◽  
Host Cells ◽  
Enteropathogenic Escherichia Coli ◽  
Sequence Of Events

The interactions that occur between pathogenic micro-organisms and their host cells are complex and intimate. We have used two enteric pathogens, Salmonella typhimurium and enteropathogenic Escherichia coli (EPEC), to examine the interactions that occur between these organisms and epithelial cells. Although these are enteric pathogens, the knowledge and techniques developed from these systems may be applied to the study of dental pathogens. Both S. typhimurium and EPEC disrupt epithelial monolayer integrity, although by different mechanisms. Both pathogens cause loss of microvilli and re-arrangement of the underlying host cytoskeleton. Despite these similarities, both organisms send different signals into the host cell. EPEC signal transduction involves generation of intracellular calcium and inositol phosphate fluxes, and activation of host tyrosine kinases that results in tyrosine phosphorylation of a 90-kDa host protein. Bacterial mutants have been identifed that are deficient in signaling to the host. We propose a sequence of events that occur when EPEC interacts with epithelial cells. Once inside a host cell, S. typhimurium remains within a vacuole. To define some of the parameters of the intracellular environment, we constructed genetic fusions of known genes with lacZ, and used these fusions as reporter probes of the intracellular vacuolar environment. We have also begun to examine the bacterial and host cell factors necessary for S. typhimurium to multiply within epithelial cells. We found that this organism triggers the formation of novel tubular lysosomes, and these structures are linked with intracellular replication.

scholarly journals Efficient Translocation of EspC into Epithelial Cells Depends on Enteropathogenic Escherichia coli and Host Cell Contact

2006 ◽  
Vol 74 (4) ◽  
pp. 2293-2303 ◽  
Author(s):  
Jorge E. Vidal ◽  
Fernando Navarro-García
Keyword(s):  
Escherichia Coli ◽  
Epithelial Cells ◽  
Host Cell ◽  
Cytopathic Effect ◽  
Cell Interaction ◽  
Cell Contact ◽  
Internalization Mechanism ◽  
Cell Cytosol ◽  
Cytoskeletal Disruption

ABSTRACT EspC is an autotransporter protein secreted by enteropathogenic Escherichia coli (EPEC). The pathogenic role of EspC in EPEC infection is unknown. We have shown that the purified EspC produces enterotoxicity and cytotoxicity; for the latter effect, EspC must be internalized. However, the internalization mechanism is unknown. Here we show that azithromycin (an inhibitor of pinocytosis), but not drugs affecting caveole-, clathrin-, or receptor-mediated endocytosis, inhibited purified EspC internalization and cytoskeletal disruption, suggesting that purified EspC is internalized by pinocytosis. Furthermore, unlike in cholera toxin, we were unable to detect a receptor on epithelial cells by pretreatment at 4°C. Upon EspC entry, it is delivered directly into the cell cytosol, as shown by the fact that drugs that inhibit intracellular trafficking had no effect on cytoskeletal disruption. All these data suggest that purified EspC internalization is not a physiological internalization mechanism; hence, we explored EspC internalization during the infection of epithelial cells by EPEC. Like other EPEC virulence factors, EspC secretion is stimulated by EPEC when it is grown in cell culture medium and enhanced by the presence of epithelial cells. Physiologically secreted EspC was efficiently internalized during EPEC and host cell interaction. Additionally, the lack of EspC internalization caused by using an isogenic mutant prevented the cytopathic effect caused by EPEC. These data suggest that EPEC uses an efficient mechanism to internalize milieu-secreted EspC into epithelial cells; once inside the cells, EspC is able to induce the cytopathic effect caused by EPEC.

scholarly journals Comprehensive Transcriptomic Analysis Identifies Novel Antiviral Factors Against Influenza A Virus Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Ao Zhou ◽  
Xia Dong ◽  
Mengyun Liu ◽  
Bin Tang
Keyword(s):  
Epithelial Cells ◽  
Virus Infection ◽  
Influenza A Virus ◽  
Broad Spectrum ◽  
Influenza A ◽  
Cell Types ◽  
Immune Defense ◽  
Host Responses ◽  
Different Cell Types ◽  
Host Genes

Influenza A virus (IAV) has a higher genetic variation, leading to the poor efficiency of traditional vaccine and antiviral strategies targeting viral proteins. Therefore, developing broad-spectrum antiviral treatments is particularly important. Host responses to IAV infection provide a promising approach to identify antiviral factors involved in virus infection as potential molecular drug targets. In this study, in order to better illustrate the molecular mechanism of host responses to IAV and develop broad-spectrum antiviral drugs, we systematically analyzed mRNA expression profiles of host genes in a variety of human cells, including transformed and primary epithelial cells infected with different subtypes of IAV by mining 35 microarray datasets from the GEO database. The transcriptomic results showed that IAV infection resulted in the difference in expression of amounts of host genes in all cell types, especially those genes participating in immune defense and antiviral response. In addition, following the criteria of P<0.05 and |logFC|≥1.5, we found that some difference expression genes were overlapped in different cell types under IAV infection via integrative gene network analysis. IFI6, IFIT2, ISG15, HERC5, RSAD2, GBP1, IFIT3, IFITM1, LAMP3, USP18, and CXCL10 might act as key antiviral factors in alveolar basal epithelial cells against IAV infection, while BATF2, CXCL10, IFI44L, IL6, and OAS2 played important roles in airway epithelial cells in response to different subtypes of IAV infection. Additionally, we also revealed that some overlaps (BATF2, IFI44L, IFI44, HERC5, CXCL10, OAS2, IFIT3, USP18, OAS1, IFIT2) were commonly upregulated in human primary epithelial cells infected with high or low pathogenicity IAV. Moreover, there were similar defense responses activated by IAV infection, including the interferon-regulated signaling pathway in different phagocyte types, although the differentially expressed genes in different phagocyte types showed a great difference. Taken together, our findings will help better understand the fundamental patterns of molecular responses induced by highly or lowly pathogenic IAV, and the overlapped genes upregulated by IAV in different cell types may act as early detection markers or broad-spectrum antiviral targets.

scholarly journals Enterohemorrhagic Escherichia coli O157:H7 Disrupts Stat1-Mediated Gamma Interferon Signal Transduction in Epithelial Cells

2003 ◽  
Vol 71 (3) ◽  
pp. 1396-1404 ◽  
Author(s):  
Peter J. M. Ceponis ◽  
Derek M. McKay ◽  
Joyce C. Y. Ching ◽  
Perpetual Pereira ◽  
Philip M. Sherman
Keyword(s):  
Escherichia Coli ◽  
Signal Transduction ◽  
Epithelial Cells ◽  
Host Cell ◽  
Tyrosine Phosphorylation ◽  
Gamma Interferon ◽  
Enterohemorrhagic Escherichia Coli ◽  
Cell Protein ◽  
E Coli ◽  
Ifn Γ

ABSTRACT Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a clinically important bacterial enteropathogen that manipulates a variety of host cell signal transduction cascades to establish infection. However, the effect of EHEC O157:H7 on Jak/Stat signaling is unknown. To define the effect of EHEC infection on epithelial gamma interferon (IFN-γ)-Stat1 signaling, human T84 and HEp-2 epithelial cells were infected with EHEC O157:H7 and then stimulated with recombinant human IFN-γ. Cells were also infected with different EHEC strains, heat-killed EHEC, enteropathogenic E. coli (EPEC) O127:H6, and the commensal strain E. coli HB101. Nuclear and whole-cell protein extracts were prepared and were assayed by an electrophoretic mobility shift assay (EMSA) and by Western blotting, respectively. Cells were also processed for immunofluorescence to detect the subcellular localization of Stat1. The EMSA revealed inducible, but not constitutive, Stat1 activation upon IFN-γ treatment of both cell lines. The EMSA also showed that 6 h of EHEC O157:H7 infection, but not 30 min of EHEC O157:H7 infection, prevented subsequent Stat1 DNA binding induced by IFN-γ, whereas infection with EPEC did not. Immunoblotting showed that infection with EHEC, but not infection with EPEC, eliminated IFN-γ-induced Stat1 tyrosine phosphorylation in both dose- and time-dependent fashions and disrupted inducible protein expression of the Stat1-dependent gene interferon regulatory factor 1. Immunofluorescence revealed that EHEC infection did not prevent nuclear accumulation of Stat1 after IFN-γ treatment. Also, Stat1 tyrosine phosphorylation was suppressed by different EHEC isolates, including intimin-, type III secretion- and plasmid-deficient strains, but not by HB101 and heat-killed EHEC. These findings indicate the novel disruption of host cell signaling caused by EHEC infection but not by EPEC infection.

scholarly journals A diarrheal pathogen, enteropathogenic Escherichia coli (EPEC), triggers a flux of inositol phosphates in infected epithelial cells.

1994 ◽  
Vol 179 (3) ◽  
pp. 993-998 ◽  
Author(s):  
V Foubister ◽  
I Rosenshine ◽  
B B Finlay
Keyword(s):  
Escherichia Coli ◽  
Epithelial Cells ◽  
Host Cell ◽  
Tyrosine Phosphorylation ◽  
Inositol Phosphates ◽  
Protein Kinase Inhibitors ◽  
Cell Protein ◽  
Bacterial Invasion ◽  
Enteropathogenic Escherichia Coli ◽  
Cytoskeletal Rearrangement

Enteropathogenic Escherichia coli (EPEC) is a bacterial pathogen that causes diarrhea in infants by adhering to intestinal epithelial cells. EPEC induces host cell protein phosphorylation and increases intracellular calcium levels that may function to initiate cytoskeletal rearrangement. We found that EPEC triggers the release of inositol phosphates (IPs) after adherence of bacteria to cultured epithelial cells. We also demonstrated that the EPEC-induced flux of IPs precedes actin rearrangement and bacterial invasion. EPEC mutants and tyrosine protein kinase inhibitors were used to establish that formation of IPs is dependent on tyrosine phosphorylation of a 90-kD HeLa protein. Collectively these results suggest that EPEC-induced tyrosine phosphorylation of a host cell substrate(s) leads to release of IPs, which may then trigger cytoskeletal rearrangement.

scholarly journals The impact of acid stress on escherichia coli O157:H7 virulence

2021 ◽  
Author(s):  
Belinda House
Keyword(s):  
Escherichia Coli ◽  
Cell Adhesion ◽  
Epithelial Cells ◽  
Host Cell ◽  
Virulence Factors ◽  
Acid Stress ◽  
Mrna Levels ◽  
E Coli ◽  
Acid Shock ◽  
The Impact

Escherichia coli 0157:H7 infection is a leading cause of hemorrhagic colitis, and hemolytic uremic syndrome. Many opportunities for acid stress exposure exist for this food and waterborne pathogen, including gastric acid shock. Yet little is known how this affects E.coli 0157:H7 virulence. The effect of various acid stress protocols on E. coli 0157:H7 survival, verotoxin production, and the ability to adhere to host epithelial cells was examined. Brief acid shock alone at pH 3.0 decreased the host cell adhesion capability by a factor of 4.3-4.8, yet when the acid shock was preceded by adaptation at pH 5.0, a 1.6-3.2 fold enhanced adhesion of surviving organisms to epithelial cells relative to unstressed organisms was observed. However, acid stress did not affect verotoxin production. Pretreatment of acid stressed bacteria with erythromycin eliminated the acid-induced adhesion enhancement, suggesting that protein synthesis is a requirement for the enhanced adhesion observed with acid-adapted acid-shocked E.coli 0157:H7. Real time PCR analysis of locus for enterocyte effacement (LEE)-encoded virulence factors, intimin and EspA, revealed no significant upregulation for the acid stress treatments associated with the increased host cell adhesion. On the contrary, elevated mRNA levels for both intimin and EspA were observed for bacteria subjected to brief acid shock alone even though the host-cell adhesion was significatly decreased with these treatments. These results suggest that complex regulation mechanisms for LEE encoded virulence factors exists and that E. coli 0157:H7 virulence can be enhanced after acid stress through increased adhesion to host epithelial cells.

scholarly journals The impact of acid stress on escherichia coli O157:H7 virulence

2021 ◽  
Author(s):  
Belinda House
Keyword(s):  
Escherichia Coli ◽  
Cell Adhesion ◽  
Epithelial Cells ◽  
Host Cell ◽  
Virulence Factors ◽  
Acid Stress ◽  
Mrna Levels ◽  
E Coli ◽  
Acid Shock ◽  
The Impact

Escherichia coli 0157:H7 infection is a leading cause of hemorrhagic colitis, and hemolytic uremic syndrome. Many opportunities for acid stress exposure exist for this food and waterborne pathogen, including gastric acid shock. Yet little is known how this affects E.coli 0157:H7 virulence. The effect of various acid stress protocols on E. coli 0157:H7 survival, verotoxin production, and the ability to adhere to host epithelial cells was examined. Brief acid shock alone at pH 3.0 decreased the host cell adhesion capability by a factor of 4.3-4.8, yet when the acid shock was preceded by adaptation at pH 5.0, a 1.6-3.2 fold enhanced adhesion of surviving organisms to epithelial cells relative to unstressed organisms was observed. However, acid stress did not affect verotoxin production. Pretreatment of acid stressed bacteria with erythromycin eliminated the acid-induced adhesion enhancement, suggesting that protein synthesis is a requirement for the enhanced adhesion observed with acid-adapted acid-shocked E.coli 0157:H7. Real time PCR analysis of locus for enterocyte effacement (LEE)-encoded virulence factors, intimin and EspA, revealed no significant upregulation for the acid stress treatments associated with the increased host cell adhesion. On the contrary, elevated mRNA levels for both intimin and EspA were observed for bacteria subjected to brief acid shock alone even though the host-cell adhesion was significatly decreased with these treatments. These results suggest that complex regulation mechanisms for LEE encoded virulence factors exists and that E. coli 0157:H7 virulence can be enhanced after acid stress through increased adhesion to host epithelial cells.

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