John Dahl;William C. Davis;Kun Taek Park;Mary Jo Hamilton
发明人:
William C. Davis,Mary Jo Hamilton,John Dahl,Kun Taek Park
申请号：
US12668651
公开号：
US08784842B2
申请日:
2008.07.14
申请国别(地区):
US
年份:
2014
代理人:
摘要：
Particular aspects provide efficient allelic exchange methods to generate directed mutations within genes of slow-growing stains of mycobacteria (e.g., Mycobacterium avium subsp. paratuberculosis (Map), Map 10 or GFP-expressing Map K-10) using a phage-delivery system, and demonstrate high efficiency allelic exchange. Additional exemplary aspects provide non-naturally occurring slow-growing strains of mycobacteria (e.g., Map, M. bovis, M. tuberculosis) having at least one gene deletion (e.g., pknG, relA, lsr2, panC, panD, proC, trpD, sapM (MAP3432), lysA_1, leuD, and leuC, and deletion mutants at the orthologous loci of two known virulence genes in pathogenic mycobacteria (relA and pknG) and one gene related to colony morphology and biofilm formation in fast growing mycobacteria (lsr2) were made. Further aspects provide novel vaccines comprising such deletion mutants, or portions thereof, and methods for making said vaccines. Yet further aspects provide methods for protecting a mammal from virulent Map, M. bovis, or M. tuberculosis, comprising treating the mammal with the inventive vaccines.
