Pathogenic mycobacteria resist lysosomal delivery after uptake into macrophages, allowing them to survive intracellularly. We found that the eukaryotic-like serine/threonine protein kinase G from pathogenic mycobacteria was secreted within macrophage phagosomes, inhibiting phagosome-lysosome fusion and mediating intracellular survival of mycobacteria. Inactivation of protein kinase G by gene disruption or chemical inhibition resulted in lysosomal localization and mycobacterial cell death in infected macrophages. Besides identifying a target for the control of mycobacterial infections, these findings suggest that pathogenic mycobacteria have evolved eukaryotic-like signal transduction mechanisms capable of modulating host cell trafficking pathways.

Mycobacteria are intracellular pathogens that can survive within macrophage phagosomes, thereby evading host defense strategies by largely unknown mechanisms. We have identified a WD repeat host protein that was recruited to and actively retained on phagosomes by living, but not dead, mycobacteria. This protein, termed TACO, represents a component of the phagosome coat that is normally released prior to phagosome fusion with or maturation into lysosomes. In macrophages lacking TACO, mycobacteria were readily transported to lysosomes followed by their degradation. Expression of TACO in nonmacrophages prevented lysosomal delivery of mycobacteria and prolonged their intracellular survival. Active retention of TACO on phagosomes by living mycobacteria thus represents a mechanism preventing cargo delivery to lysosomes, allowing mycobacteria to survive within macrophages.

We demonstrate a method for quantitatively probing the local low-frequency dielectric constant of thin insulating films by nanoscale capacitance microscopy. The calibrated capacitance-distance curves are measured on the dielectric film and analyzed by using a tip-sample capacitance model here proposed. Applied to SiO2 films as small as 1×1μm2 area and 20–30nm thickness, the method gives a dielectric constant on the submicron scale in agreement with the value determined on the large scale. The observed precision is set by the capacitance noise level of the instrument and the tip radius.

Propagation of light beams through scattering or multimode systems may lead to the randomization of the spatial coherence of the light. Although information is not lost, its recovery requires a coherent interferometric reconstruction of the original signals, which have been scrambled into the modes of the scattering system. Here we show that we can automatically unscramble optical beams that have been arbitrarily mixed in a multimode waveguide, undoing the scattering and mixing between the spatial modes through a mesh of silicon photonics tuneable beam splitters. Transparent light detectors integrated in a photonic chip are used to directly monitor the evolution of each mode along the mesh, allowing sequential tuning and adaptive individual feedback control of each beam splitter. The entire mesh self-configures automatically through a progressive tuning algorithm and resets itself after significantly perturbing the mixing, without turning off the beams. We demonstrate information recovery by the simultaneous unscrambling, sorting and tracking of four mixed modes, with residual cross-talk of −20 dB between the beams. Circuit partitioning assisted by transparent detectors enables scalability to meshes with a higher port count and to a higher number of modes without a proportionate increase in the control complexity. The principle of self-configuring and self-resetting in optical systems should be applicable in a wide range of optical applications.