Investigating bacteriophages as a novel multiple-hurdle measure against Campylobacter: field trials in commercial broiler plants.

Campylobacter mitigation along the food production chain is considered effective for minimizing the public health burden of human campylobacteriosis. This study is the first combining different measures in a multiple-hurdle approach, using drinking water additives and feed additives in single and combined application schemes in commercial broiler plants. Broiler chickens in the study groups were naturally contaminated with Campylobacter. Application of an organic acid blend via drinking water, consisting of sodium propionate, potassium sorbate, and sodium diacetate, resulted in significant reductions of up to 4.9 log10 CFU/mL in fecal samples and in cecal samples at slaughter. The application of a phage mixture, consisting of Fletchervirus phage NCTC 12673 and Firehammervirus phage vB_CcM-LmqsCPL1/1, resulted in reductions of up to 1.1 log10 CFU/mL in fecal samples 1 day after dosing. The sole administration of curcumin via feed resulted in small and inconsistent reductions. In the group receiving a combination of all tested measures, reductions of up to 1.1 log10 CFU/mL were observed. Based on the results of our field trials, it was shown that both the sole application and the combined application of mitigation measures in primary production can reduce the Campylobacter load in broiler chickens, while no synergism could be observed.

Porphyromonas gingivalis-mediated signaling through TLR4 mediates persistent HIV infection of primary macrophages.

Periodontal infections contribute to HIV-associated co-morbidities in the oral cavity and provide a model to interrogate the dysregulation of macrophage function, inflammatory disease progression, and HIV replication during co-infections. We investigated the effect of Porphyromonas gingivalis on the establishment of HIV infection in monocyte-derived macrophages. HIV replication in macrophages was significantly repressed in the presence of P. gingivalis. This diminished viral replication was due partly to a decrease in the expression of integrated HIV provirus. HIV repression depended upon signaling through TLR4 as knock-down of TLR4 with siRNA rescued HIV expression. Importantly, HIV expression was reactivated upon removal of P. gingivalis. Our observations suggest that exposure of macrophages to Gram-negative bacteria influence the establishment and maintenance of HIV persistence in macrophages through a TLR4-dependent mechanism.

Glycyl-tRNA synthetase specifically binds to the poliovirus IRES to activate translation initiation.

Adaptation to the host cell environment to efficiently take-over the host cell's machinery is crucial in particular for small RNA viruses like picornaviruses that come with only small RNA genomes and replicate exclusively in the cytosol. Their Internal Ribosome Entry Site (IRES) elements are specific RNA structures that facilitate the 5' end-independent internal initiation of translation both under normal conditions and when the cap-dependent host protein synthesis is shut-down in infected cells. A longstanding issue is which host factors play a major role in this internal initiation. Here, we show that the functionally most important domain V of the poliovirus IRES uses tRNA(Gly) anticodon stem-loop mimicry to recruit glycyl-tRNA synthetase (GARS) to the apical part of domain V, adjacent to the binding site of the key initiation factor eIF4G. The binding of GARS promotes the accommodation of the initiation region of the IRES in the mRNA binding site of the ribosome, thereby greatly enhancing the activity of the IRES at the step of the 48S initiation complex formation. Moonlighting functions of GARS that may be additionally needed for other events of the virus-host cell interaction are discussed.