UropathogenicEscherichia coliEpigenetically Manipulate Host Cell Death Pathways

Abstract

Urinary tract infections caused by uropathogenic Escherichia coli (UPEC) pathovars belong to the most frequent infections in human. It is well established that UPEC can subvert innate immune responses, but the role of UPEC in interfering with host cell death pathways is not known. Here, we show that UPEC abrogates activation of the host cell prosurvival protein kinase B signaling pathway, which results in the activation of mammalian forkhead box O (FOXO) transcription factors. Although FOXOs were localized in the nucleus and showed increased DNA-binding activity, no change in the expression levels of FOXO target genes were observed. UPEC can suppress BIM expression induced by LY249002, which results in attenuation of caspase 3 activation and blockage of apoptosis. Mechanistically, BIM expression appears to be epigenetically silenced by a decrease in histone 4 acetylation at the BIM promoter site. Taken together, these results suggest that UPEC can epigenetically silence BIM expression, a molecular switch that prevents apoptosis.

Epigenetic Mechanisms Regulate Innate Immunity against Uropathogenic and Commensal-Like Escherichia coli in the Surrogate Insect Model Galleria mellonella

“…Histone acetylation in G. mellonella differed qualitatively (spectrum of histone markers) and quantitatively (level of HAT/HDAC gene expression and abundance of the corresponding modified histones) following infection with the ABU and UPEC strains. The transcriptional induction of HDACs correlates with lower levels of H3 and H4 acetylation, with the exception of H4K5 acetylation, which specifically increased within 1 h of infection with the UPEC strain (40). After 24 h, we observed the hyperacetylation of histone H3K9, supporting similar observations in a mammalian model for Staphylococcus aureus infection (41).…”

Characterization of the Micro-Environment of the Testis that Shapes the Phenotype and Function of Testicular Macrophages

“…Quantitative real time PCR (qRT-PCR) was performed as previously described (4,25). The primer sequences are listed in Table I.…”

“…Following treatments, cell lysates and immunoblot analyses were performed as previously described (25). The Abs are listed in Table II.…”

“…For liquid-liquid extraction, 200-ml samples were incubated with extraction buffer containing 600 ml of ethyl acetate, 100 ml of 150 mM EDTA, and 20 ml of internal standard solution (25 4 ]-6-keto-PGF 1a in methanol). The samples were homogenized using a Mixer Mill MM400 (Retsch, Haan, Germany) and centrifuged at 20,000 3 g for 150 s. The extraction was repeated, and extraction solvents were removed at 45˚C under a gentle stream of nitrogen and stored at 280˚C until measurement.…”

UropathogenicEscherichia colivirulence factor hemolysin A causes programmed cell necrosis by altering mitochondrial dynamics

“…The prototype RTX poreforming toxin HlyA, frequently encoded by strains of UPEC, has distinct effects on host cells aside from outright lysis (12,13). Although it has been long known that HlyA has proinflammatory, cytolytic, and cytotoxic properties, many recent studies have shown that HlyA can also subvert the innate immune response by suppressing secretion of proinflammatory cytokines and by manipulating host survival signaling pathways, including NF-kB, MAPK, and AKT (12,14,15).…”