These data suggest that mediators synthesized by the pathogen during infection regulate both protective as well as detrimental responses
to the host. Thus, discovery and characterization of Mtb-secreted proteins could be an approach to identify novel therapeutic and diagnosis targets as well as biomarkers of disease. Lectins are classically defined as a family of proteins with the ability to specifically bind carbohydrate moieties. A number of pathogens have been demonstrated to express GPCR Compound Library manufacturer such molecules, which are involved in recognition and invasion processes 17, 18. For example, Pseudomonas aeruginosa produces several membrane-associated lectins that promote attachment to epithelial cells and contribute to its virulence 19. In addition, bacterial lectins could be released into the extracellular milieu and play an important role during infection as demonstrated by experiments using Bordetella18. These data suggest that both membrane-expressed and secreted lectins participate in host–microbial interactions. In the case of Mtb, the heparin-binding hemagglutinin adhesin (HBHA) is one of the most studied cell surface-expressed lectins
and it has been shown to be critical for bacterial dissemination in vivo20. Moreover, the existence of at least 11 hypothetical lectins from Mtb21 suggests that these molecules may be an important component of the host–mycobacteria interplay. Consistent with this, Trichostatin A nmr Sitaxentan active TB (ATB) patients have been found to display increased levels
of anti-HBHA Ab during active disease 22, 23, suggesting that mycobacterial lectins may elicit specific immune responses. We have utilized a previously generated non-redundant lectin data bank 24 in order to identify lectins from Mtb, a major human pathogen. In the present study, we have demonstrated a secreted 13 kDa ricin-like lectin from Mtb (sMTL-13). sMTL-13 was detected in pleural biopsies from ATB patients and led to an increased IFN-γ production by PBMC from patients during active disease. Importantly, ATB patients display high titers of serum IgG against sMTL-13, a response found to be rapidly decreased following successful treatment. These data report a secreted Mtb lectin with antigenic activity in human TB and suggest it may be useful as a biomarker of disease therapy. We have previously generated a non-redundant lectin database for searching lectin domains from Arabidopsis thaliana genome 24. To further evaluate the presence of such domains in an important human pathogen, Mtb, we have adapted this database and identified a single hypothetical lectin encoded by the Rv1419 gene. Figure 1A shows the bioinformatics characterization of the Rv1419 gene. Its open reading frame (ORF) contains 474 nucleotides and the aa sequence encodes a hypothetical protein of 157 residues containing a signal peptide and a predicted molecular mass of 16.8 kDa.