Dataset Information

Induction of macrophage pyroptosis-related factors by pathogenic E. coli high pathogenicity island (HPI) in Yunnan Saba pigs.

ABSTRACT:

Background

Pyroptosis plays a pivotal role in the pathogenesis of many inflammatory diseases. The molecular mechanism by which pyroptosis is induced in macrophages following infection with pathogenic E. coli high pathogenicity island (HPI) will be evaluated in our study.

Results

After infection with the HPI⁺/HPI^- strains and LPS, decreased macrophage cell membrane permeability and integrity were demonstrated with propidium iodide (PI) staining and the lactate dehydrogenase (LDH) assay. HPI⁺/HPI^--infection was accompanied by upregulated expression levels of NLRP3, ASC, caspase-1, IL-1β, IL-18 and GSDMD, with significantly higher levels detected in the HPI⁺ group compared to those in the HPI^- group (P < 0.01 or P < 0.05). HPI⁺ strain is more pathogenic than HPI^- strain.

Conclusion

Our findings indicate that pathogenic E. coli HPI infection of Saba pigs causes pyroptosis of macrophages characterized by upregulated expression of pyroptosis key factors in the NLRP3/ASC/caspase-1 signaling pathway, direct cell membrane pore formation, and secretion of the inflammatory factor IL-1β and IL-18 downstream of NLRP3 and caspase-1 activation to enhance the inflammatory response.

SUBMITTER: Shan C

PROVIDER: S-EPMC7938518 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Publications

Induction of macrophage pyroptosis-related factors by pathogenic E. coli high pathogenicity island (HPI) in Yunnan Saba pigs.

Shan Chunlan C Miao Shushu S Liu Chaoying C Zhang Bo B Zhao Weiwei W Wang Hao H Yang Wei W Cha Jinlong J Zhao Ru R Xiao Peng P Gao Hong H

BMC veterinary research 20210307 1

<h4>Background</h4>Pyroptosis plays a pivotal role in the pathogenesis of many inflammatory diseases. The molecular mechanism by which pyroptosis is induced in macrophages following infection with pathogenic E. coli high pathogenicity island (HPI) will be evaluated in our study.<h4>Results</h4>After infection with the HPI<sup>+</sup>/HPI<sup>-</sup> strains and LPS, decreased macrophage cell membrane permeability and integrity were demonstrated with propidium iodide (PI) staining and the lactate ...[more]

PMID: 33678162

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Project description:The high-pathogenicity island irp-HPI is widespread in Vibrionaceae and encodes the siderophore piscibactin, as well as the regulator PbtA that is essential for its expression. In this work, we aim to study whether PbtA directly interacts with irp-HPI promoters. Furthermore, we hypothesize that PbtA, and thereby the acquisition of irp-HPI island, may also influence the expression of other genes elsewhere in the bacterial genome. To address this question, an RNAseq analysis was conducted to identify differentially expressed genes after pbtA deletion in Vibrio anguillarum RV22 genetic background. The results showed that PbtA not only modulates the irp-HPI genes but also modulates the expression of a plethora of V. anguillarum core genome genes, inducing nitrate, arginine, and sulfate metabolism, T6SS1, and quorum sensing, while repressing lipopolysaccharide (LPS) production, MARTX toxin, and major porins such as OmpV and ChiP. The direct binding of the C-terminal domain of PbtA to piscibactin promoters (PfrpA and PfrpC), quorum sensing (vanT), LPS transporter wza, and T6SS structure- and effector-encoding genes was demonstrated by electrophoretic mobility shift assay (EMSA). The results provide valuable insights into the regulatory mechanisms underlying the expression of irp-HPI island and its impact on Vibrios transcriptome, with implications in pathogenesis.IMPORTANCEHorizontal gene transfer enables bacteria to acquire traits, such as virulence factors, thereby increasing the risk of the emergence of new pathogens. irp-HPI genomic island has a broad dissemination in Vibrionaceae and is present in numerous potentially pathogenic marine bacteria, some of which can infect humans. Previous works showed that certain V. anguillarum strains exhibit an expanded host range plasticity and heightened virulence, a phenomenon linked to the acquisition of the irp-HPI genomic island. The present work shows that this adaptive capability is likely achieved through comprehensive changes in the transcriptome of the bacteria and that these changes are mediated by the master regulator PbtA encoded within the irp-HPI element. Our results shed light on the broad implications of horizontal gene transfer in bacterial evolution, showing that the acquired DNA can directly mediate changes in the expression of the core genome, with profounds implications in pathogenesis.

Dataset Information

Induction of macrophage pyroptosis-related factors by pathogenic E. coli high pathogenicity island (HPI) in Yunnan Saba pigs.

Background

Results

Conclusion

Publications

Induction of macrophage pyroptosis-related factors by pathogenic E. coli high pathogenicity island (HPI) in Yunnan Saba pigs.

Similar Datasets

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