RESUMEN
Phages are known as a promising method to combat antimicrobial resistance (AMR) in the human and veterinary sector. Use of phage aerosols enormously increases the application field, although the impact on the infectivity of phages during nebulization needs to be evaluated. In this study S. infantis was treated on plates and chicken skin with nebulized phage particles of the Myoviridae type, identified by transmission electron microscopy, using a commercial nebulizer primarily used for H2O2 disinfection. The reduction of bacterial number by aerosol applied phage particles was evaluated. It could clearly be shown that the phage particles were able to infect Salmonella after being nebulized using ultrasound technology. Further studies on other types of phages as well as other conditions must be performed to standardize the aerosolic application of phages.
RESUMEN
Histone deacetylases (HDACs) target acetylated lysine residues in histone and non-histone proteins. HDACs are implicated in the regulation of genomic stability, cell cycle, cell death and differentiation and thus critically involved in tumorigenesis. Further, HDACs regulate T-cell development and HDAC inhibitors (HDACis) have been approved for clinical use in some T-cell malignancies. Still, the exact targets and mechanisms of HDAC inhibition in cancer are understudied. We isolated tumor cell lines from a transgenic mouse model of anaplastic large cell lymphoma (ALCL), a rare T-cell lymphoma, and abrogated HDAC activity by treatment with the HDACis Vorinostat and Entinostat or Cre-mediated deletion of Hdac1. Changes in overall protein expression as well as histone and protein acetylation were measured following Hdac1 deletion or pharmacological inhibition using label-free liquid chromatography mass spectrometry (LC-MS/MS). We found changes in overall protein abundance and increased acetylation of histones and non-histone proteins, many of which were newly discovered and associated with major metabolic and DNA damage pathways. For non-histone acetylation, we mapped a total of 1204 acetylated peptides corresponding to 603 proteins, including chromatin modifying proteins and transcription factors. Hyperacetylated proteins were involved in processes such as transcription, RNA metabolism and DNA damage repair (DDR). The DDR pathway was majorly affected by hyperacetylation following HDAC inhibition. This included acetylation of H2AX, PARP1 and previously unrecognized acetylation sites in TP53BP1. Our data provide a comprehensive view of the targets of HDAC inhibition in malignant T cells with general applicability and could have translational impact for the treatment of ALCL with HDACis alone or in combination therapies.