Enterotoxigenic Escherichia coli infection promotes apoptosis in piglets

Xia, Yaoyao; Peng, Bin; Liu, Shaojuan; Chen, Shuai; Yin, Jie; Liu, Gang; Tang, Zhiyi; Ren, Wenkai

doi:10.1016/j.micpath.2018.09.032

Cited by 24 publications

(18 citation statements)

References 24 publications

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“…Among these executioners, caspase 3 is extremely important as both intrinsic and extrinsic pathways converge at caspase 3 [ 53 ]. In this study, E. coli K88 challenge significantly elevated the expression levels of caspase 3 in the PIEC-J2 cells, which was consistent with a previous study on piglets [ 54 ]. However, DEFB118 can downregulate the expression levels of caspase 3.…”

Section: Discussionsupporting

confidence: 93%

Expression and Functional Characterization of a Novel Antimicrobial Peptide: Human Beta-Defensin 118

Lin

Xie

Chen

et al. 2020

BioMed Research International

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Purpose. β-Defensin 118 (DEFB118) is a novel host defense peptide (HDP) identified in humans. To evaluate its potentials for future utilization, the DEFB118 gene was expressed in Escherichia coli (E. coli) and the recombinant protein was fully characterized. Methods. The DEFB118 protein was obtained by heterologous expression using E. coli Rosetta (DE3). Antibacterial activity of DEFB118 was determined by using various bacterial strains. IPEC-J cells challenged by E. coli K88 were used to determine its influences on inflammatory responses. Results. The E. coli transformants yielded more than 250 μg/mL DEFB118 protein after 4 h induction by 1.0 mM IPTG. The DEFB118 was estimated by SDS-PAGE to be 30 kDa, and MALDI-TOF analysis verified that it is a human β-defensin 118. Importantly, the DEFB118 showed antimicrobial activities against both Gram-negative bacteria (E. coli K88 and E. coli DH5α) and Gram-positive bacteria (S. aureus and B. subtilis), with a minimum inhibitory concentration (MIC) of 4 μg/mL. Hemolytic assays showed that DEFB118 had no detrimental impact on cell viability. Additionally, DEFB118 was found to elevate the viability of IPEC-J2 cells upon E. coli K88 challenge. Moreover, DEFB118 significantly decreased cell apoptosis in the late apoptosis phase and downregulated the expression of inflammatory cytokines such as IL-1β and TNF-α in IPEC-J2 cell exposure to E. coli K88. Conclusions. These results suggested a novel function of the mammalian defensins, and the antibacterial and anti-inflammatory properties of DEFB118 may allow it as a potential substitute for conventionally used antibiotics or drugs.

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Section: Discussionsupporting

confidence: 93%

Expression and Functional Characterization of a Novel Antimicrobial Peptide: Human Beta-Defensin 118

Lin

Xie

Chen

et al. 2020

BioMed Research International

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“…The family of caspases can be further divided into initiator (caspases 8, 9, 10) and executioner (caspases 3, 6, 7) [52]. Among these executioners, caspase3 is extremely important as both intrinsic and extrinsic pathways converge at caspase3 [53].In this study, E. coli k88 challenge significantly elevated the expression levels of caspase3 in the PIEC-J2 cells, which was consistent with previous study on piglets [54]. However, DEFB118 can down-regulate the expression levels of caspase3.…”

Section: Discussionsupporting

confidence: 92%

Expression and functional characterization of a novel antimicrobial peptide: human beta-defensin118

Xie

Chen

et al. 2020

Preprint

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Background: β-defensin 118 (DEFB118 ) is a novel host defence peptide (HDP) identified in human. To evaluate its potentials for future utilization, the DEFB118 gene was expressed in Escherichia coli ( E. coli ) and the recombinant protein was fully characterized. Methods: The DEFB118 protein was obtained by heterologous expression using E. coli Rosetta (DE3). Antibacterical activity of DEFB118 were determined by using various bacterial strains. IPEC-J cells challenged by E. coli K88 were used to determine its influences on inflammatory responses. Results: The E. coli transformants yielded more than 250 mg/mL D EFB118 protein after 4 h induction by 1.0 mM IPTG. The DEFB118 was estimated by SDS-PAGE to be 30 kDa, and MALDI-TOF analysis verified it is a human β-defensin 118. Importantly, the DEFB118 showed antimicrobial activities against both Gram-negative bacteria ( E. coli K88 and E. coli DH5α) and Gram-positive bacteria ( S. aureus and B. subtilis ), with a minimum inhibitory concentration (MIC) of 4 μg/mL. Hemolytic assays showed that DEFB118 had no detrimental impact on cell viability. Additionally, DEFB118 was found to elevate the viability of IPEC-J2 cells upon E. coli K88 challenge. Moreover, DEFB118 significantly decreased cell apoptosis in the late apoptosis phase and down-regulated the expression of inflammatory cytokines such as the IL-1β and TNF-a in the IPEC-J2 cells exposure to E. coli K88. Conclusions: These results suggested a novel function of the mammalian defensins, and the anti-bacterial and anti-inflammatory properties of DEFB118 may allow it a potential substitute for conventionally used antibiotics or drugs.

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“…Therefore, the inhibition of GPR109A on inflammatory response can be regarded as a potential mechanism to maintain the integrity of the barrier. An alternative mechanism is that ETEC promotes apoptosis in epithelial cells ( 35 , 36 ). However, the activation of GPR109A or sodium butyrate treatment can effectively inhibit the apoptosis of epithelial cells ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

G Protein-Coupled Receptor 109A Maintains the Intestinal Integrity and Protects Against ETEC Mucosal Infection by Promoting IgA Secretion

et al. 2021

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Several studies have reported an intricate link between the G protein-coupled receptor 109A (GPR109A) and intestinal health. Upon activation, induced by butyric acid and β-hydroxybutyric acid, GPR109A regulates the expression of tight junction proteins, exerts anti-inflammatory effects, and maintains the integrity of the intestinal barrier. However, its function and the mechanism of action in combating the infection caused by exogenous pathogenic microorganisms remain unclear. This study established an animal model of infection by oral enterotoxigenic Escherichia coli (ETEC) gavage to examine the underlying mechanism(s) and protective effects of GPR109A on the intestinal tract. Experimental GPR109A–/–and GPR109A+/+ mice were orally administered with 1 × 109 colony-forming units (CFUs) of ETEC, and changes in body weight were then observed. The colonization and translocation of ETEC in the intestine were detected by the plate counting method. The expression of tight junction proteins and the levels of inflammatory factors and secretory IgA (SIgA) in the intestine were detected by quantitative real-time polymerase chain reaction (q-PCR), western blotting, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry. The results demonstrated that GPR109A–/–mice were more susceptible to ETEC infection, showing more severe inflammatory reactions and intestinal damage. Moreover, the secretion of IgA in the intestinal tract of GPR109A+/+ mice was significantly increased after ETEC infection, whereas the IgA levels in GPR109A–/–mice did not change significantly. We added 5 g/L sodium butyrate to the drinking water of all mice. The GPR109A+/+ mice were protected against ETEC infection and no effect was observed in GPR109A–/–mice. Similarly, sodium butyrate increased the SIgA content in the gut of the GPR109A+/+ mice and no effect was observed in GPR109A–/–mice. In conclusion, activated GPR109A is effective against the colonization and translocation of ETEC in the gut and maintains the integrity of the intestinal barrier, possibly by promoting the secretion of intestinal IgA.

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Enterotoxigenic Escherichia coli infection promotes apoptosis in piglets

Cited by 24 publications

References 24 publications

Expression and Functional Characterization of a Novel Antimicrobial Peptide: Human Beta-Defensin 118

Expression and Functional Characterization of a Novel Antimicrobial Peptide: Human Beta-Defensin 118

Expression and functional characterization of a novel antimicrobial peptide: human beta-defensin118

G Protein-Coupled Receptor 109A Maintains the Intestinal Integrity and Protects Against ETEC Mucosal Infection by Promoting IgA Secretion

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