Mycobacterium tuberculosis suppresses host antimicrobial peptides by dehydrogenating L-alanine.

Antimicrobial peptides (AMPs), ancient scavengers of bacteria, are very poorly induced in macrophages infected by Mycobacterium tuberculosis (M. tuberculosis), but the underlying mechanism remains unknown. Here, we report that L-alanine interacts with PRSS1 and unfreezes the inhibitory effect of PRSS1 on the activation of NF-κB pathway to induce the expression of AMPs, but mycobacterial alanine dehydrogenase (Ald) Rv2780 hydrolyzes L-alanine and reduces the level of L-alanine in macrophages, thereby suppressing the expression of AMPs to facilitate survival of mycobacteria. Mechanistically, PRSS1 associates with TAK1 and disruptes the formation of TAK1/TAB1 complex to inhibit TAK1-mediated activation of NF-κB pathway, but interaction of L-alanine with PRSS1, disables PRSS1-mediated impairment on TAK1/TAB1 complex formation, thereby triggering the activation of NF-κB pathway to induce expression of AMPs. Moreover, deletion of antimicrobial peptide gene ß-defensin 4 (Defb4) impairs the virulence by Rv2780 during infection in mice. Both L-alanine and the Rv2780 inhibitor, GWP-042, exhibits excellent inhibitory activity against M. tuberculosis infection in vivo. Our findings identify a previously unrecognized mechanism that M. tuberculosis uses its own alanine dehydrogenase to suppress host immunity, and provide insights relevant to the development of effective immunomodulators that target M. tuberculosis.

Near-infrared long-range surface plasmon resonance in a D-shaped honeycomb microstructured optical fiber coated with Au film.

Long-range surface plasmon resonances (LRSPRs) are featured with longer propagation and deeper penetration, compared with conventional surface plasmon resonances (SPRs). Thus, LRSPR-based fiber sensors are considered to have great potential for highly sensitive detection in chemistry or biomedicine areas. Here, we propose and demonstrate a near-infrared LRSPR sensor based on a D-shaped honeycomb microstructured optical fiber (MOF) directly coated with gold film. Although there is no additional heterogeneous buffer layer, the optical field of the long-range surface plasmon polariton (LRSPP) mode penetrates strongly into the analyte region. Thus the effective refractive index of the LRSPP mode depends highly on the analyte's material refractive index and an abnormal dispersion relationship between the LRSPP mode and MOF's y-polarized core mode is observed. The mechanism of the LRSPR excitation in the coupling zone is attributed to an avoided crossing effect between these two modes. It also results in the generation of a narrow-bandwidth peak in the loss spectrum of the core mode. Further discussion shows that the resonance wavelength is mainly determined by the core size that is contributed by the MOF's cladding pitch, silica-web thickness and planar-layer-silica thickness together. It indicates that the operation wavelength of the proposed LRSPR device can be flexibly tuned in a broadband wavelength range, even longer than 2 µm, through appropriately designing the MOF's structural parameters. Finally, the proposed LRSPR sensor shows the highest wavelength sensitivity of 14700 nm/RIU and highest figure of merit of 475 RIU-1 for the analyte refractive index range from 1.33 to 1.39.