Antimicrobial peptides (AMPs), critical components of the innate immune system, are widely distributed throughout the animal and plant kingdoms. They can protect against a broad array of infection-causing agents, such as bacteria, fungi, parasites, viruses, and tumor cells, and also exhibit immunomodulatory activity. AMPs exert antimicrobial activities primarily through mechanisms involving membrane disruption, so they have a lower likelihood of inducing drug resistance. Extensive studies on the structure-activity relationship have revealed that net charge, hydrophobicity, and amphipathicity are the most important physicochemical and structural determinants endowing AMPs with antimicrobial potency and cell selectivity. This review summarizes the recent advances in AMPs development with respect to characteristics, structure-activity relationships, functions, antimicrobial mechanisms, expression regulation, and applications in food, medicine, and animals.

Antimicrobial peptides: Promising alternatives in the post feeding antibiotic era.

Bacterial cell wall muramyl dipeptide (MDP) and glucosaminyl-MDP (GMDP) are potent activators of innate immunity. Two receptor targets, NOD2 and YB1, have been reported; we investigated potential overlap of NOD2 and YB1 pathways. Separate knockdown of NOD2 and YB1 demonstrates that both contribute to GMDP induction of NF-κB expression, a marker of innate immunity, although excess YB1 led to induction in the absence of NOD2. YB1 and NOD2 co-migrated on sucrose gradient centrifugation, and GMDP addition led to the formation of higher molecular mass complexes containing both YB1 and NOD2. Co-immunoprecipitation demonstrated a direct interaction between YB1 and NOD2, a major recombinant fragment of NOD2 (NACHT-LRR) bound to YB1, and complex formation was stimulated by GMDP. We also report subcellular colocalization of NOD2 and YB1. Although YB1 may have other binding partners in addition to NOD2, maximal innate immunity activation by muramyl peptides is mediated via an interaction between YB1 and NOD2.

https://journals.sagepub.com/doi/pdf/10.1177/1753425916668982

Muramyl peptides activate innate immunity conjointly via YB1 and NOD2.

The Bioprospecting of Microbial-Derived Antimicrobial Peptides for Sustainable Agriculture

Monoclonal antibodies against the recombinant YB-1 protein were obtained and characterized. These antibodies are capable of specific detection of YB-1 protein in the enzyme-linked immunosorbent assay, Western blot analysis, and immunocytochemistry. Using phage display technology, a peptide interacting with the YB-1 protein was found. Based on monoclonal antibodies МАYB-1-2 and a peptide as part of the bacteriophage structural protein, a test system was developed for the quantitative determination of YB-1 protein in blood serum. The detection limit of the developed test system is 0.3 ng/mL.

Application of Monoclonal Antibodies and Phage Display Technology for YB-1 Protein Analysis

It was shown that in the presence of the recombinant protein YB-1, the response of human leukemic monocytes THP-1 to stimulation with muramylpeptide GMDP and LPS was significantly reduced, which was manifested in a decrease of the relative content of mRNA encoding the following molecules: proinflammatory cytokine IL-1β, innate immunity receptors NOD2 and TLR4, their adapters RIP2 and MyD88, and the p105/p50 (NF-κB1) and p100/p52 (NF-κB2) subunits of the NF-κB transcription factor. The inhibiting effect of YB-1 protein also follows from the lower level of p65 protein (RelA NF-kB) in nuclei of cells stimulated with LPS and GMDP/LPS. Inactivation of the NOD2 gene in the THP-1 cells resulted in a decrease of IL-1β mRNA in response to GMDP, LPS, and GMDP/LPS. At the same time, inactivation of the YB-1 gene led to an increased relative content of IL-1β and other molecules’ mRNA upon stimulation with GMDP. However, in response to stimulation with LPS and GMDP/LPS the level of IL-1β mRNA decreased in comparison to the initial cells, which indicates that YB-1 is necessary for the induction of an optimal immune response. Thus, the data obtained indicate the involvement of YB-1 in the innate immunity receptor system as a negative regulator of NOD2 receptor activity.

Inhibitory Effect of Transcription Factor YB-1 in the Development of Signal from an Innate Immunity Receptor NOD2

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/j.febslet.2015.05.028

E.V. Svirshchevskaya

Papers

Innate immunity: Bacterial cell‐wall muramyl peptide targets the conserved transcription factor YB‐1