No abstract

According to the World Allergy Organization (WAO), approximately 20% of the global population suffers from allergies. As per ongoing investigations, their pervasiveness is expanding comprehensively. Allergic diseases are significant because of the high prevalence and constant increase in their costs and adverse effects on human life. Probiotics are proposed as an intervention for the prevention and treatment of allergic diseases. Various mechanisms are considered for the anti-allergic effects of probiotic properties, like detecting related molecular patterns, including DNA motifs or lipopolysaccharides (LPS) of the bacteria, through interaction with host immune systems by Toll-like receptors. In this chapter, the microbiome, allergy, and the role of immunomodulatory probiotics against allergy are discussed.

Background: Lactic acid bacteria (LAB), which are important probiotics, play a fundamental role in ensuring the health of the gastrointestinal tract, maintaining the microbiome balance, and preventing the gastrointestinal (GI) tract disorder. One of the effective mechanisms in the bacterial-host interaction is related to the action of the enzyme sortase A and Sortase Dependent Proteins (SDPs). Sortase plays an important role in the stabilization and retention of the probiotic in the gut by exposing various SDPs on the bacterial surface proteins which is involved in the attachment of bacteria to the host intestine and retention in the gut.Methods: The present study aimes to identify and investigate the abundance of sortase A-dependent proteins (SDPs) in lactic acide bacteria, as well as the frequency analysis of X residue in the sortase recognition and cleavage LPXTG motif and its effect on the interaction between sortase and SDPs. For this purpose, genomic and proteomic sequences of 165 LABs including 119 Lactobacilli, 29 Enterococci, 8 Lactococci, 5 Carnobacteria, and 4 Leuconostocs, were extracted from UniProt and Genome NCBI databases,. for this, we designed ProtScreen software with the ability to recognize a specific motif and domain in the proteome, which is available at http://nigebprotscreen.com/. Also interactions between sortase A and LPXTG motif with 18 different amino acids in X position were determined using in silico approach. The structure of the sortase A enzyme and a SDP in Lactobacillus acidophilus was used for docking using HADDOCK and CABS-dock toolsResults: In this study, out of 165 LABs reference proteomes, there were 25 SDP-free strains. Among the 140 strains with SDPs, 707 proteins were found with the potential to function as SDPs. In this way, ProtScreen software with the ability to recognize a specific motif and domain in the proteome, which is available at http://nigebprotscreen.com/ was designed. Also a database including 707 SDPs in Lactobacillus, Enterococcus, Lactococcus, Carnobacterium, and Leuconostoc strains was designed which is available in the project section at online ProtScreen software. Our results showed that the most abundant amino acid in X position in the LPXTG motif among 165(LABs) is glutamine (Q). Results of SDPs and sortase A docking using HADDOCK and CABS-dock tools, showed that the highest binding energy is related to the glutamine, where a positive relationship between frequency of amino acids and binding energy was observed. Therefore, our data shows that why glutamine in nature and during evolution, has been selected as the best amino acid for X site in LPXTG motif.Conclusions: The results of the present research and similar studies could be useful in better understanding the role of sortase A and SDPs in the studies on the mechanisms related to the interactions between bacteria and the host, including longer probiotic persistence in the gut.