Molecular Mimicry Mapping in Streptococcus pneumoniae: Cues for Autoimmune Disorders and Implications for Immune Defense Activation

Abstract

Streptococcus pneumoniae contributes to a range of infections, including meningitis, pneumonia, otitis media, and sepsis. Infections by this bacterium have been associated with the phenomenon of molecular mimicry, which, in turn, may contribute to the induction of autoimmunity. In this study, we utilized a bioinformatics approach to investigate the potential for S. pneumoniae to incite autoimmunity via molecular mimicry. We identified 13 S. pneumoniae proteins that have significant sequence similarity to human proteins, with 11 of them linked to autoimmune disorders such as psoriasis, rheumatoid arthritis, and diabetes. Using in silico tools, we predicted the sequence as well as the structural homology among these proteins. Database mining was conducted to establish links between these proteins and autoimmune disorders. The antigenic, non-allergenic, and immunogenic sequence mimics were employed to design and validate an immune response via vaccine construct design. Mimic-based vaccine construct can prove effective for immunization against the S. pneumoniae infections. Immune response simulation and binding affinity was assessed through the docking of construct C8 to human leukocyte antigen (HLA) molecules and TLR4 receptor, with promising results. Additionally, these mimics were mapped as conserved regions on their respective proteins, suggesting their functional importance in S. pneumoniae pathogenesis. This study highlights the potential for S. pneumoniae to trigger autoimmunity via molecular mimicry and the possibility of vaccine design using these mimics for triggering defense response.

Mining Autoimmune-Disorder-Linked Molecular-Mimicry Candidates in Clostridioides difficile and Prospects of Mimic-Based Vaccine Design: An In Silico Approach

“…To identify potential regions involved in mimicry, the proteins were aligned to uncover regions of similarity with a minimum length of 10 amino acids [ 16 ]. RMSD was employed as a scoring metric to assess the structural similarity of the peptides.…”

“…The vaccine construct was designed according to the previously described methodology [ 16 ], using suitable linkers, adjuvants, and binders. They were subjected to another round of evaluation according to properties like antigenicity, toxicity, allergenicity, etc.…”

“…The entire set of proteins from the human and C. difficile S-0253 (reference strain ASM1888508v1) samples was obtained from Uniprot (https://www.uniprot.org/proteomes/ UP000005640 (accessed on 31 May 2023)) and the NCBI database (GenBank accession: CP076401.1; accessed 31 May 2023), respectively. To identify potential homologous proteins, a local installation of BLAST was utilized, applying a threshold of ≥50% identity and ≥100-bit score to retain proteins for further analysis [16].…”

“…Evolutionary analysis revealed majority of residues of both sequence mimics are highly conserved (Figure 2). Mimic-based vaccine design is an innovative approach that utilizes synthetic peptides or proteins to mimic specific antigens of pathogens [16]. By presenting these mimics to the immune system, it can generate targeted immune responses against the actual pathogen.…”

“…Numerous studies have investigated the molecular mimicry between human proteins associated with autoimmune disorders and pathogen-derived proteins [ 8 , 9 , 10 , 11 , 12 , 13 ]. These investigations have revealed several mechanisms that contribute to the initiation and perpetuation of autoimmune responses [ 14 , 15 , 16 ]. Specific pathogen proteins have been found to share sequence motifs with host proteins involved in autoimmune disorders, enabling the activation of autoreactive T cells [ 14 , 17 ].…”