Transferrin receptor 1 is a supplementary receptor that assists transmissible gastroenteritis virus entry into porcine intestinal epithelium

Abstract Background Transmissible gastroenteritis virus (TGEV), the etiologic agent of transmissible gastroenteritis, infects swine of all ages causing vomiting and diarrhea, in newborn piglets the mortality rate is near 100%. Intestinal epithelial cells are the primary target cells of TGEV. Transferrin receptor 1 (TfR1), which is highly expressed in piglets with anemia, may play a role in TGEV infection. However, the underlying mechanism of TGEV invasion remains largely unknown. Results Our study investigated the possibility that TfR1 can serve as a receptor for TGEV infection and enables the invasion and replication of TGEV. We observed that TGEV infection promoted TfR1 internalization, clustering, and co-localization with TfR1 early in infection, while TfR1 expression was significantly down-regulated as TGEV infection proceeded. TGEV infection and replication were inhibited by occluding TfR1 with antibodies or by decreasing TfR1 expression. TGEV infection increased in TGEV-susceptible ST or IPEC-J2 cell lines and TGEV-resistant Caco-2 cells when porcine TfR1 was over-expressed. Finally, we found that the TGEV S1 protein interacts with the extracellular region of TfR1, and that pre-incubating TGEV with a protein fragment containing the extracellular region of TfR1 blocked viral infection. Conclusions Our results support the hypothesis that TfR1 is an additional receptor for TGEV and assists TGEV invasion and replication

Synthetic Cationic Lipopeptide Can Effectively Treat Mouse Mastitis Caused by <i>Staphylococcus aureus</i>

Mastitis caused by Staphylococcus aureus (S. aureus) in dairy cows is one of the most common clinical diseases in dairy cattle. Unfortunately, traditional antibiotic treatment has resulted in the emergence of drug-resistant strains of bacteria, making this disease more difficult to treat. Therefore, novel lipopeptide antibiotics are becoming increasingly important in treating bacterial diseases, and developing novel antibiotics is critical in controlling mastitis in dairy cows. We designed and synthesized three cationic lipopeptides with palmitic acid, all with two positive charges and dextral amino acids. The lipopeptides’ antibacterial activity against S. aureus was determined using MIC and scanning electron microscopy. The safety concentration range of lipopeptides for clinical usage was then estimated using the mouse erythrocyte hemolysis assay and CCK8 cytotoxicity. Finally, lipopeptides with high antibacterial activity and minimal cytotoxicity were selected for the treatment experiments regarding mastitis in mice. The observation of histopathological changes, bacterial tissue load and expression of inflammatory factors determined the therapeutic effects of lipopeptides on mastitis in mice. The results showed that all three lipopeptides displayed some antibacterial activity against S. aureus, with C16dKdK having a strong antibacterial impact and being able to treat the mastitis induced by S. aureus infection in mice within a safe concentration range. The findings of this study can be used as a starting point for the development of new medications for the treatment of mastitis in dairy cows

Synthetic surfactin analogues have improved anti-PEDV properties.

Surfactin has antiviral activity against various enveloped viruses by inhibiting viral membrane fusion. However, the potential utility of surfactin as an antiviral drug is limited by its cytotoxicity. In this study, 10 surfactin analogues were obtained by chemical synthesis and evaluated to determine their anti-PEDV activities, hemolytic activities, and critical micelle concentrations. The main goal of our study was to develop a safer drug; a surfactin analogue with high anti-PEDV activity and low hemolytic activity. Compared with surfactin, one of the analogues we developed, SLP5, has lower hemolytic activity, with the same antiviral activity. The selectivity index of SLP5 is 52, while the SI for surfactin is 4, in other words, the safe and effective concentration range of SLP5 is 12 times greater than that of surfactin. Like surfactin, SLP5 has a direct antiviral effect on PEDV. Structurally, SLP5 is a linear lipopeptide with three carboxyl groups. Surfactin derivatives similar to SLP5 could be obtained by lactone bond hydrolyzation of surfactin, as well as total synthesis

Characterization and virulence clustering analysis of extraintestinal pathogenic Escherichia coli isolated from swine in China

Abstract Background Swine extraintestinal pathogenic Escherichia coli (ExPEC) is an important pathogen that leads to economic and welfare costs in the swine industry worldwide, and is occurring with increasing frequency in China. By far, various virulence factors have been recognized in ExPEC. Here, we investigated the virulence genotypes and clonal structure of collected strains to improve the knowledge of phylogenetic traits of porcine ExPECs in China. Results We isolated 64 Chinese porcine ExPEC strains from 2013 to 14 in China. By multiplex PCR, the distribution of isolates belonging to phylogenetic groups B1, B2, A and D was 9.4%, 10.9%, 57.8% and 21.9%, respectively. Nineteen virulence-related genes were detected by PCR assay; ompA, fimH, vat, traT and iutA were highly prevalent. Virulence-related genes were remarkably more prevalent in group B2 than in groups A, B1 and D; notably, usp, cnf1, hlyD, papA and ibeA were only found in group B2 strains. Genotyping analysis was performed and four clusters of strains (named I to IV) were identified. Cluster IV contained all isolates from group B2 and Cluster IV isolates had the strongest pathogenicity in a mouse infection model. As phylogenetic group B2 and D ExPEC isolates are generally considered virulent, multilocus sequence typing (MLST) analysis was performed for these isolates to further investigate genetic relationships. Two novel sequence types, ST5170 and ST5171, were discovered. Among the nine clonal complexes identified among our group B2 and D isolates, CC12 and CC95 have been indicated to have high zoonotic pathogenicity. The distinction between group B2 and non-B2 isolates in virulence and genotype accorded with MLST analysis. Conclusion This study reveals significant genetic diversity among ExPEC isolates and helps us to better understand their pathogenesis. Importantly, our data suggest group B2 (Cluster IV) strains have the highest risk of causing animal disease and illustrate the correlation between genotype and virulence

Additional file 2: Table S1. of Characterization and virulence clustering analysis of extraintestinal pathogenic Escherichia coli isolated from swine in China

Statistical analysis of associations between virulence-associated factores(VFs). P values by Fisher’s exact test, shown only where < .10. P < .10 reflects statistical significance ;P values between .01 and .05 reflect possible statistical significance. (DOCX 19 kb

Additional file 4: Table S3. of Characterization and virulence clustering analysis of extraintestinal pathogenic Escherichia coli isolated from swine in China

The information of isolates identified as ExPEC with Johnson et al’s criterion (DOCX 15 kb

Heritability and recursive influence of host genetics on the rumen microbiota drive body weight variance in male Hu sheep lambs

Abstract Background Heritable rumen microbiota is an important modulator of ruminant growth performance. However, no information exists to date on host genetics-rumen microbiota interactions and their association with phenotype in sheep. To solve this, we curated and analyzed whole-genome resequencing genotypes, 16S rumen-microbiota data, and longitudinal body weight (BW) phenotypes from 1150 sheep. Results A variance component model indicated significant heritability of rumen microbial community diversity. Genome-wide association studies (GWAS) using microbial features as traits identified 411 loci-taxon significant associations (P < 10−8). We found a heritability of 39% for 180-day-old BW, while also the rumen microbiota likely played a significant role, explaining that 20% of the phenotypic variation. Microbiota-wide association studies (MWAS) and GWAS identified four marker genera (Bonferroni corrected P < 0.05) and five novel genetic variants (P < 10−8) that were significantly associated with BW. Integrative analysis identified the mediating role of marker genera in genotype influencing phenotype and unravelled that the same genetic markers have direct and indirect effects on sheep weight. Conclusions This study reveals a reciprocal interplay among host genetic variations, the rumen microbiota and the body weight traits of sheep. The information obtained provide insights into the diverse microbiota characteristics of rumen and may help in designing precision microbiota management strategies for controlling and manipulating sheep rumen microbiota to increase productivity. Video Abstrac