title: Reactivation of dormant "non-culturable" Mycobacterium tuberculosis developed in vitro after injection in mice: both the dormancy depth and host genetics influence the outcome.
abstract: Three stocks of Mycobacterium tuberculosis H37Rv were cultured in vitro under prolonged hypoxic or acidified conditions until partial or complete loss of the capacity to form colonies on agar medium was achieved. Such dormant "non-culturable" mycobacteria were assessed for the growth resuscitation after intra-tracheal injection into mice of the two inbred strains with different genetic susceptibility to M. tuberculosis-triggered disease: hyper-susceptible I/St and relatively resistant B6. The results indicate that bacteria which are able to resuscitate spontaneously in liquid medium in vitro started to multiply in organs of infected mice, and that the outcome of such infection strongly depended upon the level of genetic TB susceptibility. However, dormant bacteria required inducers for resuscitation in vitro lost the capacity to multiply even in genetically susceptible mice. The established model of dormancy/reactivation is suitable for the studying host-pathogen interactions and testing vaccine and drug candidates specifically targeting latent TB.
authors.affiliation: A.N. Bach Institute of Biochemistry, Russian Academy of Sciences, Moscow, Russia. Electronic address: mshleeva@inbi.ras.ru.
authors.forename: Margarita
authors.initials: M
authors.lastname: Shleeva
authors.affiliation: Central Institute for Tuberculosis, Moscow, Russia.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Kondratieva
authors.affiliation: Central Institute for Tuberculosis, Moscow, Russia.
authors.forename: Elvira
authors.initials: E
authors.lastname: Rubakova
authors.affiliation: A.N. Bach Institute of Biochemistry, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Galina
authors.initials: G
authors.lastname: Vostroknutova
authors.affiliation: A.N. Bach Institute of Biochemistry, Russian Academy of Sciences, Moscow, Russia.
authors.forename: Arseny
authors.initials: A
authors.lastname: Kaprelyants
authors.affiliation: Central Institute for Tuberculosis, Moscow, Russia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Apt
mesh_terms: D000818:Animals; D005260:Female; D020022:Genetic Predisposition to Disease; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000502:physiology*; D014376:Tuberculosis / Q000235:genetics* / Q000382:microbiology*
keywords: Inbred mouse strains; Latency; Reactivation; Tuberculosis