Does host mucin - Salmonella adhesion interaction steer disease invasiveness?: A comparative study using common clinically important servers

Deniz, Tunalıer
Salmonella enterica subsp. enterica (Salmonella) which is a Gram-negative, rod- shaped, and motile bacterium, is one of the most prevalent foodborne pathogens. World Health Organization (WHO) highlighted that at least 100 million people suffer from salmonellosis annually. Salmonella has over 2600 serovars which are characterized in terms of host specificity or clinical manifestation. Host mucin 1 (MUC1) is a receptor for Salmonella giant adhesin Salmonella intestine infection (SiiE). The presence of siiE might affect the course of the disease. The severity of salmonellosis might be affected by MUC1 and SiiE interaction. In this study, it’s hypothesized that the degree of invasiveness through this interaction varies regarding host specificity of Salmonella. Determining protein-protein interactions (PPIs) between SiiE adhesin of Salmonella and its host receptor MUC1 to observe binding characteristics of different Salmonella serovars is the aim of the study. The gene sequences of siiE of previously whole genome sequenced (WGS) local METU Salmonella isolates, as well as universal Salmonella isolates retrieved from National Center for Biotechnology Information (NCBI). METU isolates were selected by their original hosts, molecular subtypes, and frequency of making disease in humans in Türkiye. Similar approach was used to select serovars world-wide from NCBI; serovars representing the most and the least observation rates for making disease in humans among the continents were used. By using sequence data of previously WGS METU Salmonella isolates (n=47), primer sets were designed to conduct multiplex PCR to detect presence of siiE gene. Overall, 78 representative Salmonella isolates were subjected to screening of the gene. According to the multiplex PCR results, all these isolates (n=78) have siiE, therefore it is concluded that siiE is an abundant gene among Salmonella serovars. For in silico analysis, genome data of important 37 Salmonella isolates were obtained from NCBI. Since SiiE is the biggest protein in Salmonella proteome, including 5559 amino acids, a representative region of this protein which is bacterial immunoglobulin-like domains 50th to 52nd (BIg50:52), was used for further analysis. A phylogenetic tree was constructed from SiiE BIg50:52 to observe amino acid substitutions in Salmonella isolates (n=84). Total of 20 clusters were observed in the phylogenetic tree and the most prevalent substitutions were detected on residues 5113 and 5336. Also, secondary structures of WGS METU Salmonella isolates (n=47) and selected isolates from NCBI (n=5) were determined by using threading approach to furtherly use in docking with rigid body method. From docking between SiiE and MUC1, PPIs showed that except disulfide bridges other interactions have a role on binding. Moreover, no correlation was observed for interaction of MUC1 and SiiE BIg50:52 of different Salmonella serovars in terms of host specificity. Finally, it was remarked that SiiE’s residues 5174 and 5175 may have a vital role on host – receptor interaction between SiiE of Salmonella and MUC1 of Homo sapiens. This study contributed to a better understanding of Salmonella – host interactions and observing the effect of Salmonella diversity on binding characteristics and invasiveness.
Citation Formats
T. Deniz, “Does host mucin - Salmonella adhesion interaction steer disease invasiveness?: A comparative study using common clinically important servers,” M.S. - Master of Science, Middle East Technical University, 2023.