bambermycins and Disease-Models--Animal

The minimum inhibitory concentration of bambermycin on three porcine Helicobacter suis strains was shown to be 8 μg/mL. The effect of in-feed medication with this antibiotic on the course of a gastric infection with one of these strains, the host response and the gastric microbiota was determined in mice, as all of these parameters may be involved in gastric pathology. In H. suis infected mice which were not treated with bambermycin, an increased number of infiltrating B-cells, T-cells and macrophages in combination with a Th2 response was demonstrated, as well as a decreased parietal cell mass. Compared to this non-treated, infected group, in H. suis infected mice medicated with bambermycin, gastric H. suis colonization was not altered, but a decreased number of infiltrating T-cells, B-cells and macrophages as well as downregulated expressions of IL-1β, IL-8M, IL-10 and IFN-γ were demonstrated and the parietal cell mass was not affected. In bambermycin treated mice that were not infected with H. suis, the number of infiltrating T-cells and expression of IL-1β were lower than in non-infected mice that did not receive bambermycin. Gastric microbiota analysis indicated that the relative abundance of bacteria that might exert unfavorable effects on the host was decreased during bambermycin supplementation. In conclusion, bambermycin did not affect H. suis colonization, but decreased gastric inflammation and inhibited the effects of a H. suis infection on parietal cell loss. Not only direct interaction of H. suis with parietal cells, but also inflammation may play a role in death of these gastric acid producing cells.

Topics: Animal Feed; Animals; Anti-Bacterial Agents; Bambermycins; Diet; Dietary Supplements; Disease Models, Animal; Female; Helicobacter heilmannii; Helicobacter Infections; Inflammation; Mice; Mice, Inbred BALB C; Parietal Cells, Gastric; Specific Pathogen-Free Organisms; Stomach; Swine; Swine Diseases

The ATP-dependent transporter gene abcA in Staphylococcus aureus confers resistance to hydrophobic β-lactams. In strain ISP794, abcA is regulated by the transcriptional regulators MgrA and NorG and shares a 420-nucleotide intercistronic region with the divergently transcribed pbp4 gene, which encodes the transpeptidase Pbp4. Exposure of exponentially growing cells to iron-limited media, oxidative stress, and acidic pH (5.5) for 0.5 to 2 h had no effect on abcA expression. In contrast, nutrient limitation produced a significant increase in abcA transcripts. We identified three additional regulators (SarA, SarZ, and Rot) that bind to the overlapping promoter region of abcA and pbp4 in strain MW2 and investigated their role in the regulation of abcA expression. Expression of abcA is decreased by 10.0-fold in vivo in a subcutaneous abscess model. In vitro, abcA expression depends on rot and sarZ regulators. Moenomycin A exposure of strain MW2 produced an increase in abcA transcripts. Relative to MW2, the MIC of moenomycin was decreased 8-fold for MW2ΔabcA and increased 10-fold for the MW2 abcA overexpresser, suggesting that moenomycin is a substrate of AbcA.

Topics: Abscess; Animals; Anti-Bacterial Agents; ATP-Binding Cassette Transporters; Bacterial Proteins; Bambermycins; Base Sequence; Disease Models, Animal; Electrophoretic Mobility Shift Assay; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Hydrogen-Ion Concentration; Iron; Mice; Molecular Sequence Data; Oxidative Stress; Promoter Regions, Genetic; Protein Binding; Repressor Proteins; Staphylococcal Skin Infections; Staphylococcus aureus; Stress, Physiological; Trans-Activators; Transcription Factors; Transcription, Genetic