Unexplored Arsenals of Legume Peptides With Potential for Their Applications in Medicine and Agriculture

Abstract

During endosymbiosis, bacteria live intracellularly in the symbiotic organ of their host. The host controls the proliferation of endosymbionts and prevents their spread to other tissues and organs. In Rhizobium-legume symbiosis the major host effectors are secreted nodule-specific cysteine-rich (NCR) peptides, produced exclusively in the symbiotic cells. NCRs have evolved in the Inverted Repeat Lacking Clade (IRLC) of the Leguminosae family. They are secreted peptides that mediate terminal differentiation of the endosymbionts, forming polyploid, non-cultivable cells with increased membrane permeability. NCRs form an extremely large family of peptides, which have four or six conserved cysteines but otherwise highly diverse amino acid sequences, resulting in a wide variety of anionic, neutral and cationic peptides. In vitro, many synthetic NCRs have strong antimicrobial activities against both Gram-negative and Gram-positive bacteria, including the ESKAPE strains and pathogenic fungi. The spectra and minimal bactericidal and anti-fungal concentrations of NCRs differ, indicating that, in addition to their charge, the amino acid composition and sequence also play important roles in their antimicrobial activity. NCRs attack the bacteria and fungi at the cell envelope and membrane as well as intracellularly, forming interactions with multiple essential cellular machineries. NCR-like peptides with similar symbiotic functions as the NCRs also exist in other branches of the Leguminosae family. Thus, legumes provide countless and so far unexplored sources of symbiotic peptides representing an enormous resource of pharmacologically interesting molecules.

Exopolysaccharide Characterization of Rhizobium favelukesii LPU83 and Its Role in the Symbiosis With Alfalfa

“…Despite that NCRs show toxicity for the rhizobia in vitro , they are needed for the proper differentiation of the bacteria into bacteroids ( Kondorosi et al, 2013 ; Pan and Wang, 2017 ). Furthermore, the membrane, the EPS and the LPS have been suggested as key components in the resistance to the NCRs ( Montiel et al, 2017 ; Lima et al, 2020 ). It could be hypothesized that some other difference in the LPU83 cell envelope does not allow a correct perception of NCRs or that the expression of NCRs differs between the infection of E. meliloti and LPU83, resulting in non-proper symbiotic nodules in the case of infection by LPU83.…”

Isolation of Cysteine-Rich Peptides from Citrullus colocynthis

“…Consequently, CRPs are under investigation as molecular scaffolds for engineering pharmaceutically useful peptides. CRPs have been studied from numerous plant families [39,40], and the squash family (Cucurbitaceae) is known as a rich source of these stabilized peptides [5,41]. In this study, we isolated and characterized novel CRPs from C. colocynthis a member of the Cucurbitaceae family.…”

Symbiotic NCR Peptide Fragments Affect the Viability, Morphology and Biofilm Formation of Candida Species

“…However, it is becoming increasingly apparent that peptides can have multifaceted mechanisms inhibiting various cell functions, such as nucleic acid and protein synthesis, and metabolism or cause production of reactive oxygen species and apoptosis [ 26 ]. Legume plants represent countless sources of symbiotic NCR peptides, many of which have broad ranges of antimicrobial and antifungal activities without notable toxicity on human cells [ 9 ]. Isolation of NCRs from root nodules is not feasible due to the small 1–3 mm size of nodules.…”

“…NCRs have 4 or 6 cysteines in conserved position and otherwise high divergence in their amino acid composition and sequence resulting in a great diversity in their physicochemical properties that is also reflected by the wide range of isoelectric point (pI) of peptides from 3.2 to 11.2. Many of these symbiotic NCR peptides have in vitro strong antimicrobial activities [ 9 ]. Cationic NCRs such as NCR247 (pI: 10.15) and NCR335 (pI: 11.22) show broad range and partially overlapping activities, indicating that in addition to the positive net charge, the amino acid sequence contributes to the antimicrobial properties [ 10 ].…”