Mycobacterial glycoproteins: a novel subset of vaccine candidates.

Abstract

Over the last two decades significant research efforts and resources have been devoted to identifying mycobacterial proteins of value to diagnostic assays and vaccine formulations. These scientific endeavors were often preceded by first identifying a target population of proteins, for example cytoplasmic, cell envelope, or extracellular. However, many of these endeavors have overlooked the posttranslational modifications (PTM) to which these protein subsets may be targets of. Consequently, we may be missing essential molecular information relevant to the function and antigenicity of these effector molecules, and in turn the pathobiology of these bugs. Moreover, heterologous expression of mycobacterial proteins in hosts lacking homologous PTM systems negates any functional and/or antigenic role the PTM may impart. Functional and pathogenic roles of PTMs, such as protein glycosylation, have been reported for other Gram-positive bacteria, especially in reference to mucosal pathogens (reviewed by Szymanski and Wren, 2005). Our objective in this piece is to shed light on the lack of PTM studies so that current and future researchers hunting for diagnostic and vaccine candidates shall: (i) be made aware of PTMs of mycobacterial proteins, and (ii) come to understand their growing importance to both pathobiology and immunogenicity. Interestingly, the last 5 years has only yielded 2 reports on the global analyses of mycobacterial glycoproteins, both for M. tuberculosis (Mtb), and over the last decade only a few studies demonstrated the importance of PTMs to the pathobiology and antigenicity of select proteins in Mtb, M. bovis, and Mycobacterium avium subsp. paratuberculosis (MAP). In this communication we present the opinion that in a world of cross-reactive epitopes, and high amino acid sequence similarity between M. bovis, MAP, and their saprophytic counterparts, PTM diversity amongst these species may confer a new level of epitope-specificity for select antigens. We will also highlight that in the case of protein glycosylation, the type and extent of glycosyl moieties should not been seen as having the same outcome. Furthermore, the presence or absence of the PTM of proteins included in subunit vaccine formulations or attenuated strains, may enhance or mask the processing, presentation, and immunogenicity of relevant epitopes. Collectively, these data call to action critical analyses of the components we use to formulate mycobacterial vaccines. As the vast majority of PTM studies have focused on glycosylation, this PTM will be the focal point of discussion.