C11518: Transgenic rel Tubercle Bacilli for Anti-Tuberculosis Drug ScreeningNovelty:
Transgenic guinea pig-passaged tubercle bacilli with modified rel expression levels useful for the identification of novel anti-tuberculosis therapeutics.
Value Proposition:
To date, tuberculosis (TB) infections are often unrecognized due to the ability of tubercle bacilli to develop asymptomatic latent infection; however; under circumstances when the immune response is perturbed, infections can reactivate and recrudesce into clinically active contagious tuberculosis. Hence, there is great interest in elucidating the molecular mechanisms underlying latency for an improved early-stage detection and therapy. Thus, this invention provides transgenic bacilli strains with altered expression of rel, critical for bacterial stringent response and bacilli virulence, as a valuable new research tool to screen for novel anti-tuberculosis drugs. Advantages include:
• Platform for development of novel therapeutics targeting Rel for treatment of persistent infections
• Shortening of current treatment durations using potential new combination therapies
Technical Details:
Johns Hopkins researchers have created transgenic rel tubercle bacilli strains permitting the study of small molecule Rel inhibitors as potential new therapeutics for the treatment of persistent tuberculosis infections. Mycobacterium tuberculosis infection induces cellular immune responses resulting in caseous necrosis of granulomas and bacillary death; however, stringent response can enable bacilli to survive the harsh conditions within caseating granulomas and develop a latent infection, which currently presents a major challenge for the efficient management and eradication of TB. Therefore, this invention created bacilli mutant strains altered in their expression levels of Rel, a dual function enzyme catalyzing the synthesis or hydrolysis of the alarmone (p)ppGpp governing the stringent response. Guinea pig-passaged rel deletion mutants and rel conditional strains are provided that are valuable for testing their susceptibility to various bactericidal antibiotics. Together, this provides an excellent platform to identify potential new combination therapies comprised of Rel inhibitors and bactericidal anti-tuberculosis drugs, which may permit shortening the duration of current TB chemotherapy.
Looking for Partners:
To develop and commercialize the technology as a research tool permitting the screening for novel anti-tuberculosis combination therapeutics.
Stage of Development:
Pre-Clinical
Data Availability:
Animal data
Publications/Associated Cases:
J Infect Dis. 2010 Nov 1;202(9):1397-404.
