Ability of mycobacterial pathogens to establish a persistent infection is lost by deletion of a single gene,rel, regulator of the stringent response

Abstract

AbstractStudies in a mouse model revealedMycobacterium tuberculosis(Mtb) with a deletion ofrel, regulator of the stringent response, could not establish a persistent infection. Studies in cattle with aMycobacterium. a. paratuberculosis reldeletion mutant revealed inability to establish a persistent infection was associated with development of CD8 cytotoxic T cells (CTL) that kill intracellular bacteria. Further comparative studies ex vivo withMbvCalmette-Guérin (BCG) and a BCGreldeletion mutant revealed no clear difference in development of CTL in vitro. As reported, a study of the recall response was conducted with cattle vaccinated with either BCG or with BCGrel,to determine if information could be obtained that would show how gene products under control ofrelinterfere with the CTL response to mycobacterial pathogens in vivo. The study revealed the CTL response elicited by vaccination with BCG was impaired, in comparison with the response elicited by BCGrel. Comparative analysis of the recall response ex vivo revealed the functional impairment was not associated with the timing of appearance of the recall response, expression of IFN-γ, TNF-α, IL-17, or IL-22, or molecules that mediate intracellular killing. Further studies are needed to determine how CD8 CTL functional activity is modulated in vivo by gene products regulated byrel.