Mycobacterium tuberculosis Rv1419 encodes a secreted 13 kDa lectin with immunological reactivity during human tuberculosis

Abstract

In this study, we have identified a secreted 13 kDa lectin from Mtb (Mtb, Mycobacterium tuberculosis; sMTL-13) by homology search of a non-redundant lectin database. Bioinformatic analysis revealed that sMTL-13 belongs to the ricin-type b-trefoil family of proteins containing a Sec-type signal peptide present in Mtb complex species, but not in nontuberculous mycobacteria. Following heterologous expression of sMTL-13 and generation of an mAb (clone 276.B7/IgG1j), we confirmed that this lectin is present in culture filtrate proteins from Mtb H37Rv, but not in non-tuberculous mycobacteria-derived culture filtrate proteins. In addition, sMTL-13 leads to an increased IFN-c production by PBMC from active tuberculosis (ATB) patients. Furthermore, sera from ATB patients displayed high titers of IgG Ab against sMTL-13, a response found to be decreased following successful antituberculosis therapy. Together, our findings reveal a secreted 13 kDa ricin-like lectin from Mtb, which is immunologically recognized during ATB and could serve as a biomarker of disease treatment.

Identification of mycobacterial lectins from genomic data

“…The only structural investigations reported on mycobacterial lectins so far are accounts of crystallization and preliminary X‐ray studies on a M. tuberculosis lectin20 and a M. smegmatis lectin domain21 that emanated from this laboratory. Biochemical characterization of the M. tuberculosis lectin Rv1419 has also been reported indicating its ability to agglutinate rabbit erythrocytes 83. Thus, mycobacterial lectins constitute a largely unexplored area.…”

Mycobacterium bovisBCG infection alters the macrophageN-glycome

“…Bacterial lectins could also potentially manipulate the immune response, by competing with the host lectins for the glycans present at the surface of immune cells. In particular, a ricin-type b-trefoil lectin, encoded by Rv1419 gene, has been detected in pleural effusions and granulomas of patients with active TB (42). Interestingly, Rv1419 modulates adhesion to murine and human derived macrophages and influences the intracellular growth of Mtb (43).…”

Lectins ofMycobacterium tuberculosis– rarely studied proteins

“…However, most of the proteins encoded by these genes have yet to be biochemically characterized, precluding further functional predictions. Exceptions are the secreted 13 kDa large lectin from Mtb , sMTL-13 [79–80], and the heparin-binding hemagglutinin (HBHA) [81–85], which have been previously studied in detail (see below). We subsequently discuss the association of the nine putative Mtb lectins identified by Singh et al and Abhinav et al with established lectin families [77–78], such as agglutinin-like sequences (ALS), mannose-sensitive hemagglutinin (MSHA), C-type lectins, and R-type lectins.…”

“…This secreted protein was crystallized in 2010 by Patra et al, however, a three-dimensional structure has yet to be resolved [79]. Recently Nogueira et al detected high titers of IgG antibodies against sMTL-13 in sera from TB patients, a response found to be diminished following successful antituberculosis therapy [80]. The results underline that mycobacterial lectins are expressed in vivo and might be important for Mtb infections.…”

“…BALB/c mice infected with either wild-type or HBHA-deficient Mtb displayed equivalent bacterial lung colonization, but the HBHA-deficient mutant showed reduced dissemination to other regions of the body relative to wild type, suggesting that HBHA plays an important role in extrapulmonary spread [84]. It has also been shown that antibodies directed against HBHA can limit adhesion of mycobacteria to epithelial cells in vitro and in vivo [80,83]. Interestingly, anti-HBHA antibodies have been detected in the sera of TB patients [82].…”