The In Vivo Environment Accelerates Generation of Resuscitation-Promoting Factor–Dependent Mycobacteria

Resuscitation-promoting factors are important determinants of the pathophysiology inMycobacterium tuberculosisinfection

“…At present, the precise mechanism(s) by which Rpf-dependency is generated are unknown although recent studies have shed some light. When Rpf-dependent Mtb and M. bovis BCG were isolated from sputum and mouse lung homogenates, respectively, subsequent exposure of mycobacteria to these did not induce Rpf-dependency (Mukamolova et al, 2010;Turapov et al, 2014) so suggesting contact with the pulmonary environment itself is not the critical factor. More insight came from studying the dynamics of Rpf-dependency development, which indicates a potential role for the adaptive immune response (Turapov et al, 2014).…”

“…When Rpf-dependent Mtb and M. bovis BCG were isolated from sputum and mouse lung homogenates, respectively, subsequent exposure of mycobacteria to these did not induce Rpf-dependency (Mukamolova et al, 2010;Turapov et al, 2014) so suggesting contact with the pulmonary environment itself is not the critical factor. More insight came from studying the dynamics of Rpf-dependency development, which indicates a potential role for the adaptive immune response (Turapov et al, 2014). When the lung CFU counts were measured at 24 h post infection of mice with M. bovis BCG Glaxo, no significant Rpf-dependent population was present, however, by 2 weeks Rpf-dependency had developed and persisted thereafter (Turapov et al, 2014).…”

“…Rpf-dependent mycobacteria are also generated in vivo, however the in vivo triggers for Rpf-dependency are as yet unresolved (Hu et al, 2015;Mukamolova et al, 2010;Turapov et al, 2014). Rpf-dependent mycobacteria have been grown from patients' sputum (Chengalroyen et al, 2016;Mukamolova et al, 2010) and extrapulmonary samples (O'Connor et al, 2015).…”

“…Variation in the proportion of Rpf-dependency between individuals implicates host factors in its formation (Turapov et al, 2014). At present, the precise mechanism(s) by which Rpf-dependency is generated are unknown although recent studies have shed some light.…”

“…More insight came from studying the dynamics of Rpf-dependency development, which indicates a potential role for the adaptive immune response (Turapov et al, 2014). When the lung CFU counts were measured at 24 h post infection of mice with M. bovis BCG Glaxo, no significant Rpf-dependent population was present, however, by 2 weeks Rpf-dependency had developed and persisted thereafter (Turapov et al, 2014). Notably, this correlates temporarily with the development of the adaptive immune response in mice (Vallerskog et al, 2010).…”