Dataset Information

Butyrate-mediated autophagy inhibition limits cytosolic Salmonella Infantis replication in the colon of pigs treated with a mixture of Lactobacillus and Bacillus.

ABSTRACT: Probiotics as an effective and safe strategy for controlling Salmonella infection are much sought after, while autophagy is a central issue in eliminating intracellular pathogens of intestinal epithelial cells. In this study, an animal model of colitis has been developed by infecting weaned pigs orally with a strain of Salmonella Infantis in order to illuminate the potential efficacy of a mixture of Lactobacillus and Bacillus (CBB-MIX) in the resistance to Salmonella infection by regulating butyrate-mediated autophagy. We found that CBB-MIX alleviated S. Infantis-induced colitis and tissue damage. Autophagy markers ATG5, Beclin-1, and the LC3-II/I ratio were significantly enhanced by S. Infantis infection, while treatment with CBB-MIX suppressed S. Infantis-induced autophagy. Additionally, S. Infantis-induced colonic microbial dysbiosis was restored by this treatment, which also preserved the abundance of the butyrate-producing bacteria and the butyrate concentration in the colon. A Caco-2 cell model of S. Infantis infection showed that butyrate had the same effect as the CBB-MIX in restraining S. Infantis-induced autophagy activation. Further, the intracellular S. Infantis load assay indicated that butyrate restricted the replication of cytosolic S. Infantis rather than that in Salmonella-containing vacuoles. Suppression of autophagy by knockdown of ATG5 also attenuated S. Infantis-induced cell injury. Moreover, hyper-replication of cytosolic S. Infantis in Caco-2 cells was significantly decreased when autophagy was inhibited. Our data demonstrated that Salmonella may benefit from autophagy for cytosolic replication and butyrate-mediated autophagy inhibition reduced the intracellular Salmonella load in pigs treated with a probiotic mixture of Lactobacillus and Bacillus.

SUBMITTER: Chu B

PROVIDER: S-EPMC7409499 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Butyrate-mediated autophagy inhibition limits cytosolic Salmonella Infantis replication in the colon of pigs treated with a mixture of Lactobacillus and Bacillus.

Chu Bingxin B Zhu Yaohong Y Su Jinhui J Xia Bing B Zou Yunjing Y Nie Jiawei J Zhang Wei W Wang Jiufeng J

Veterinary research 20200805 1

Probiotics as an effective and safe strategy for controlling Salmonella infection are much sought after, while autophagy is a central issue in eliminating intracellular pathogens of intestinal epithelial cells. In this study, an animal model of colitis has been developed by infecting weaned pigs orally with a strain of Salmonella Infantis in order to illuminate the potential efficacy of a mixture of Lactobacillus and Bacillus (CBB-MIX) in the resistance to Salmonella infection by regulating buty ...[more]

PMID: 32758277

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Project description:BACKGROUND: For satisfactory Salmonella control, good biosecurity along the pork production chain is crucial, although additional control measures on-farm need to be considered. This study evaluated the effect of two potential control measures against the spread of Salmonella Typhimurium via a transmission experiment with 56 piglets (3-15 weeks of age): two groups were orally vaccinated with 107 - 108 Colony Forming Units (CFU)/2 mL of a new attenuated Salmonella Typhimurium vaccine 'Salmoporc-?rfaJ' with DIVA capacities (Differentiation between Infected and Vaccinated Animals) (n?=?2x16); the feed of one group was additionally supplemented with coated calcium-butyrate salt. Two weeks post vaccination, four pigs per group were orally challenged with 107 CFU/2 mL of a Salmonella Typhimurium strain 112910a. Both groups were compared with a positive (challenged/untreated; n?=?16) and negative (unchallenged/untreated; n?=?8) control group. Until six weeks post challenge, blood, individual faecal and finally tissue samples were examined. Adjusted transmission ratios 'Ra' were estimated, based on the challenge strain isolation from faecal and/or tissue samples. RESULTS: In both intervention groups, Ra values were lower compared to the positive control group, although these differences were not significant. In the combination group DIVA vaccine?+?coated butyrate, less non-challenged contact animals excreted Salmonella and less tissue samples were found Salmonella-positive in all pigs, when compared to the positive control group (P?<?0.01). Seroconversion was detected in none of the vaccinated animals before challenge, when using a commercial lipopolysaccharide (LPS) ELISA targeting only Salmonella O-antigens, deleted in this vaccine. This was in contrast with an in-house whole-cell ELISA testing for various Salmonella antigens, in which Salmonella-specific antibodies were found pre-challenge in the serum of the vaccinated pigs. CONCLUSIONS: Both interventions showed a limited, non-significant reduction of Salmonella transmission between piglets. They may have applications towards Salmonella control and surveillance. Firstly, the number of Salmonella excreting contact pigs was significantly lower in the group where vaccination was combined with coated calcium-butyrate salt in the feed; secondly, the new vaccine confirmed its DIVA capacity. Therefore, these interventions merit further research with larger sample sizes, to optimize their use for Salmonella programmes.

Project description:Introduction:The emergence and spread of new strains of zoonotic bacteria, such as multidrug resistant (MDR) Salmonella Infantis, represent a growing health risk for humans in and outside Europe due to foodborne infections of poultry meat origin. Objectives:In order to understand genome relations of S. Infantis strains from Hungary and from different geographic regions, we performed a comprehensive genome analysis of nine Hungarian and 67 globally selected strains of S. Infantis and 26 Salmonella strains representing 13 non-Infantis serovars. Results:Analyses of whole-, and accessory genomes, showed that almost all S. Infantis strains were separated from the non-Infantis serovars. S. Infantis strains from Hungary formed subclusters based on their time of isolation. In whole genome sequence analysis, the Swiss strains of S. Infantis were closely related to each other and clustered together with subclusters of strains from Hungary, Japan, Italy, United States, and Israel. The accessory genome analysis revealed that the Swiss strains were distinct from most of the strains investigated, including the Hungarian ones. Analysis of the cloud genes offered the most detailed insight into the genetic distance and relationship of S. Infantis strains confirming that the Swiss and Hungarian strains belonged to different lineages. As expected, core genome analysis provided the least discriminatory power for analysis of S. Infantis. Genomic sequences of nine strains from Brazil, Israel, Mexico, Nigeria, and Senegal (deposited as S. Infantis) proved to be outliers from the S. Infantis clade. They were predicted to be Salmonella Rissen, Salmonella Ouakarm, Salmonella Kentucky, Salmonella Thompson, and Salmonella enterica subsp. diarizonae. Conclusion:Accessory genome of S. Infantis showed the highest diversity suggesting a faster evolution than that of the whole genomes contributing to the emergence of multiple genetic variants of S. Infantis worldwide. Accordingly, in spite of the comprehensive analysis of several genomic characteristics, no epidemiologic links between these S. Infantis strains from different countries could be established. It is also concluded that several strains originally designated as S. Infantis need in databanks reclassification.

Dataset Information

Butyrate-mediated autophagy inhibition limits cytosolic Salmonella Infantis replication in the colon of pigs treated with a mixture of Lactobacillus and Bacillus.

Publications

Butyrate-mediated autophagy inhibition limits cytosolic Salmonella Infantis replication in the colon of pigs treated with a mixture of Lactobacillus and Bacillus.

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