RESUMEN
Mycobacterium tuberculosis has evolved a highly specialized system to snatch essential nutrients from its host, among which host-derived cholesterol has been established as one main carbon source for M. tuberculosis to survive within granulomas. The uptake, catabolism, and utilization of cholesterol are important for M. tuberculosis to sustain within the host largely via remodeling of the bacterial cell walls. However, the regulatory mechanism of cholesterol uptake and its impact on bacterium fate within infected hosts remain elusive. Here, we found that M. tuberculosis LacI-type transcription regulator Rv3575c negatively regulates its mce4 family gene transcription. Overexpression of Rv3575c impaired the utilization of cholesterol as the sole carbon source by Mycobacterium smegmatis, activating the host's innate immune response and triggering cell pyroptosis. The M. smegmatis homologue of Rv3575c MSMEG6044 knockout showed enhanced hydrophobicity and permeability of the cell wall and resistance to ethambutol, suppressed the host innate immune response to M. smegmatis, and promoted the survival of M. smegmatis in macrophages and infected mouse lungs, leading to reduced transcriptional levels of TNFα and IL-6. In summary, these data indicate a role of Rv3575c in the pathogenesis of mycobacteria and reveal the key function of Rv3575c in cholesterol transport in mycobacteria.
RESUMEN
Chitosan oligosaccharides graft polycaprolactone copolymer (PHCSO-g-PCL) has been synthesized via initiating the polymerization of e-caprolactone (CL) monomer through an amino group protection route using phthaloyl chitosan oligosaccharide (PHCSO) as intermediate. The grafting reaction was carried out in Pyridine at 120 °C with the hydroxyl group of the chitosan oligosaccharide (CSO) as initiator and the tin 2-ethylhexanoate (Sn (Oct)2) as catalyst. The PHCSO-g-PCL nanoparticles with and without bovine serum albumin (BSA) drug were prepared through the self-assembled approach in Dimethylformamide (DMF) organic solvents. PHCSO-PCL copolymer was investigated by Fourier transform infrared spectroscopy (FTIR), 1H NMR spectrum and scanning electron microscopy (SEM). The physicochemical properties of the hydrophobized PHCSO-g-PCL nanoparticles were characterized by fluorescence spectroscopy and dynamic light scattering (DLS). The results of DLS showed that the hydrodynamic diameters and particle size distribution with various concentrations of PHCSO-g-PCL nanoparticles were from 69.82 nm to 195.9 nm with a narrow polydispersity factor of 0.212 to 0.172. The results of DLS also showed that the hydrodynamic diameters and particle size distribution of PHCSO-g-PCL (5 mg/ml) nanoparticles without and with BSA drug (0.4 mg/ml) were from 168.44 nm to 200.7 nm. The polydispersity factor was from 0.119 to 0.159.