ABSTRACT
Mycobacterium paratuberculosis causes Johne's disease in cattle, a chronic granulomatous enteritis for which a killed vaccine is commercially available. We present a case of a veterinarian who had an unintended needle-stick with injection of vaccine material. He developed a granulomatous dermatitis with acid-fast bacilli identified on pathology of affected tissue. It is important for health-care providers who care for patients at risk for unintended vaccine exposure to be aware of the possible sequelae after exposure and provide appropriate treatment based on the severity of the injury and subsequent tissue response.
Subject(s)
Dermatitis , Mycobacterium avium subsp. paratuberculosis , Paratuberculosis , Vaccines , Animals , Cattle , Dermatitis/etiology , Humans , MaleSubject(s)
Dermatology , Curriculum , Dermatology/education , Humans , Prospective Studies , StudentsABSTRACT
The evolution from microarrays to transcriptome deep-sequencing (RNA-seq) and from RNA interference to gene knockouts using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPRs) and Transcription Activator-Like Effector Nucleases (TALENs) has provided a new experimental partnership for identifying and quantifying the effects of gene changes on drug resistance. Here we describe the results from deep-sequencing of RNA derived from two cytarabine (Ara-C) resistance acute myeloid leukemia (AML) cell lines, and present CRISPR and TALEN based methods for accomplishing complete gene knockout (KO) in AML cells. We found protein modifying loss-of-function mutations in Dck in both Ara-C resistant cell lines. CRISPR and TALEN-based KO of Dck dramatically increased the IC50 of Ara-C and introduction of a DCK overexpression vector into Dck KO clones resulted in a significant increase in Ara-C sensitivity. This effort demonstrates the power of using transcriptome analysis and CRISPR/TALEN-based KOs to identify and verify genes associated with drug resistance.
