Introduction of quality management in a National Reference Laboratory in Germany.

Background: High quality diagnostic services are crucial for tuberculosis (TB) diagnosis, treatment and control. A strong laboratory quality management system (QMS) is critical to ensuring the quality of testing and results. Recent initiatives to improve TB laboratory quality have focused on low and middle-income countries, but similar issues also apply to high-income countries.

A piperidinol-containing molecule is active against by inhibiting the mycolic acid flippase activity of MmpL3.

, the causative agent of tuberculosis, remains a major human pathogen, and current treatment options to combat this disease are under threat because of the emergence of multidrug-resistant and extensively drug-resistant tuberculosis. High-throughput whole-cell screening of an extensive compound library has recently identified a piperidinol-containing molecule, PIPD1, as a potent lead compound against Herein, we show that PIPD1 and related analogs exert bactericidal activity against the strain mc6230 and also against a panel of multidrug-resistant and extensively drug-resistant clinical isolates of , suggesting that PIPD1's mode of action differs from those of most first- and second-line anti-tubercular drugs. Selection and DNA sequencing of PIPD1-resistant mycobacterial mutants revealed the presence of single-nucleotide polymorphisms in , encoding an inner membrane-associated mycolic acid flippase in Results from functional assays with spheroplasts derived from a strain lacking the endogenous gene but harboring the homolog indicated that PIPD1 inhibits the MmpL3-driven translocation of trehalose monomycolate across the inner membrane without altering the proton motive force.