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Crosstalks between NOD1 and Histone H2A Contribute to Host Defense against Streptococcus agalactiae Infection in Zebrafish.

ABSTRACT: Correlation studies about NOD1 and histones have not been reported. In the present study, we report the functional correlation between NOD1 and the histone H2A variant in response to Streptococcus agalactiae infection. In zebrafish, NOD1 deficiency significantly promoted S. agalactiae proliferation and decreased larval survival. Transcriptome analysis revealed that the significantly enriched pathways in NOD1^-/- adult zebrafish were mainly involved in immune and metabolism. Among 719 immunity-associated DEGs at 48 hpi, 74 DEGs regulated by NOD1 deficiency were histone variants. Weighted gene co-expression network analysis identified that H2A, H2B, and H3 had significant associations with NOD1 deficiency. Above all, S. agalactiae infection could induce the expression of intracellular histone H2A, as well as NOD1 colocalized with histone H2A, both in the cytoplasm and cell nucleus in the case of S. agalactiae infection. The overexpression of H2A variants such as zfH2A-6 protected against S. agalactiae infection and could improve cell survival in NOD1-deficient cells. Furthermore, NOD1 could interact with zfH2A-6 and cooperate with zfH2A-6 to inhibit the proliferation of S. agalactiae. NOD1 also showed a synergetic effect in inducing the expression of many antibacterial genes, especially antibacterial pattern recognition receptors PGRP2, PGRP5, and PGRP6. Collectively, these results firstly highlight the roles of NOD1 deficiency in the regulation of immune-related and metabolic pathways, and the correlation between zebrafish NOD1 and histone H2A variant in the defense against S. agalactiae infection.

SUBMITTER: Wu X

PROVIDER: S-EPMC8300774 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Streptococcus agalactiae is a common pathogen in aquaculture that disrupts the balance of the intestinal microbiota and threatens fish health, causing enormous losses to the aquaculture industry. In this study, we isolated and screened a Lactococcus lactis KUST48 (LLK48) strain with antibacterial effect against S. agalactiae in vitro and used it as a potential probiotic to explore its therapeutic effect on zebrafish (Danio rerio) infected with S. agalactiae. This study divided zebrafish into 3 groups: control group, injected with phosphate-buffered saline; infection group, injected with S. agalactiae; and treatment group, treated with LLK48 after S. agalactiae injection. Then, the 16S rRNA gene sequences of the intestinal microbiota of these 3 groups were sequenced using Illumina high-throughput sequencing technology. The results showed that the relative abundance of intestinal bacteria was significantly decreased in the infection group, and a high relative abundance of S. agalactiae was observed. The relative abundance of the intestinal microbiota was increased in the treatment group, with a decrease in the relative abundance of S. agalactiae compared to that in the control group. In the Cluster of Orthologous Groups of proteins function classification, the relative abundance of each biological function in the infection group was significantly lower than that of the control and treatment groups, showing that LLK48 has a positive therapeutic effect on zebrafish infected with S. agalactiae. This study provides a foundation for exploring the pathogenic mechanism of S. agalactiae on fish and their intestinal symbionts, and also presents a new approach for the treatment of S. agalactiae infections in fish aquaculture systems. IMPORTANCE L. lactis KUST48 (LLK48) with a bacteriostatic effect against S. agalactiae was isolated from tilapia intestinal tracts. S. agalactiae infection significantly reduced the relative abundance of intestinal bacteria and various physiological functions in zebrafish intestines. LLK48 demonstrated infection and subsequent therapeutic effects on the S. agalactiae infection in the zebrafish intestine. Therefore, the potential probiotic LLK48 can be considered as a therapeutic treatment for S. agalactiae infections in aquaculture, which can reduce the use of antibiotics and help maintain fish health.

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Crosstalks between NOD1 and Histone H2A Contribute to Host Defense against Streptococcus agalactiae Infection in Zebrafish.

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