The Enigmatic PE/PPE Multigene Family of Mycobacteria and Tuberculosis Vaccination

Abstract

The genome of Mycobacterium tuberculosis, the bacterium responsible for the disease tuberculosis, contains an unusual family of abundant antigens (PE/PPEs). To date, certain members of this multigene family occur only in mycobacteria that cause disease. It is possible that the numerous proteins encoded by these mycobacterial genes dictate the immune pathogenesis of this bacterial pathogen. There is also evidence that some of these antigens are present at the cell surface and that they affect the pathology and immunology of the organism in many ways. Also, they elicit both antibodies and T cells, they may be involved in antigenic variation, and they may be good candidates for vaccines and drugs. However, since they are plentiful and extremely homologous, these PE/PPEs are very challenging to study, and it is difficult to be certain what role(s) they have in the pathogenesis of tuberculosis. Consequently, how to develop treatments like vaccines using these antigens as candidates is complex.

Expression and regulatory networks of Mycobacterium tuberculosis PE/PPE family antigens

“…The exclusive presence of the PE/PPE family in pathogenic mycobacteria has attracted many researchers to this protein family (Gey van Pittius et al, ). The primary origin, regulation, and physiological role of some PE/PPE family proteins have been well characterized and reviewed (Akhter, Ehebauer, Mukhopadhyay, & Hasnain, ; Brennan, ; Brennan & Delogu, ; Fishbein, van Wyk, Warren, & Sampson, ; Kohli et al, ; Mohareer, Tundup, & Hasnain, ; Sampson, ; Tian & Jian‐Ping, ; Vordermeier et al, ). PE/PPE gene pairs are frequently associated with the esx gene clusters, which encode type VII secretion (T7S) systems (Ates, Houben, & Bitter, ; Gey van Pittius et al, ).…”

Structural Basis and Designing of Peptide Vaccine using PE-PGRS Family Protein of Mycobacterium ulcerans – An Integrated Vaccinomics Approach

“…In the current study, we designed a multi-epitope vaccine using the potent T and B-cell epitopes derived from the highest antigenic PE-PGRS family protein of M. ulcerans. The PE-PGRS proteins belong to the PE family of conserved mycobacterial protein featured by the presence of a polymorphic GC-rich repeating units (Sampson 2011;Brennan 2017). Although the function(s) of PE-PGRS protein is still remain elusive, emerging evidences support the association of PE/PPE proteins with several steps of mycobacterial pathogenesis (Sampson 2011;Bottai and Brosch 2009).…”

“…Although the function(s) of PE-PGRS protein is still remain elusive, emerging evidences support the association of PE/PPE proteins with several steps of mycobacterial pathogenesis (Sampson 2011;Bottai and Brosch 2009). In addition, PE-PGRSs interact with TLR2 receptor to activate the dendritic cells (DCs), macrophages and production of inflammatory cytokines like tumor necrosis factor-alpha (TNF-α) that promote apoptosis and necrosis of host cells (Brennan 2017;Dheenadhayalan, Delogu, and Brennan 2006). Further, they elicit both T-cells and cross-reactive antibodies; and may involve in antigenic variation (Brennan 2017).…”

“…Therefore, TLR2 is essential for provoking an immune response against M. ulcerans (Lee et al 2009). In addition, PE-PGRS protein interacts with TLR2 on macrophages and antigen presenting cells such as dendritic cells (Brennan 2017). Moreover, TLR agonists (i.e., lipoproteins, lipopolysaccharides, monophosphoryl lipid A, and mannan-protein) are well-known to be used as vaccine adjuvants (Gnjatic, Sawhney, and Bhardwaj 2010; Kumar, Sunagar, and Gosselin 2019).…”

The PE/PPE Multigene Family of Mycobacteria and TB Vaccines

“…Since their discovery, scientists speculated about the role the members in this family might play in Mtb pathogenesis, immunity, evolution, and antigenic variation. Brennan et al [1] in Issue 6 of Infection and Immunity, summarizes what is known about PE/PPEs with a particular focus on how they could be used in new TB vaccines. In fact, two TB vaccines presently being studied in clinical trials, GSK's M72 and IDRI's ID93, each contain a PPE protein.…”