Probiotic effect of Lactococcus lactis subsp. cremoris RPG-HL-0136 on intestinal mucosal immunity in mice

Lactococcus lactis subsp. cremoris is a lactic acid bacterium commonly used in the cheese manufacturing industry. It is known to produce antibacterial peptides and has recently received attention for its role as a probiotic strain. Here, we report the isolation of a new strain, Lactococcus lactis subsp. cremoris RPG-HL-0136 (RPG0136) from dried compost, which exhibits strong antibacterial activity. When RPG0136 was fed to mice, it increased the intestinal population of two beneficial bacteria, Lactobacillus and Bifidobacterium, whereas it decreased the intestinal population of two harmful bacteria, Bacteroides and Enterobacter. In addition, it increased the concentration of short-chain fatty acids, including acetic acid, propionic acid, and butyric acid, with a simultaneous decrease in pH, and accelerated the catabolic degradation of proteins, lipids, and starch. Lastly, RPG0136 increased the plasma IgG and intestinal mucosal SIgA concentrations and upregulated Reg3r, MUC1, and MUC2 expression to improve the intestinal mucosal immune function. The results of this study suggest that RPG0136 is a potential probiotic strain that supports the growth of a beneficial microbiome by promoting the synthesis of organic acids and enhancing intestinal immune function.

Self-Control of Inflammation during Tail Regeneration of Lizards

Lizards can spontaneously regenerate their lost tail without evoking excessive inflammation at the damaged site. In contrast, tissue/organ injury of its mammalian counterparts results in wound healing with a formation of a fibrotic scar due to uncontrolled activation of inflammatory responses. Unveiling the mechanism of self-limited inflammation occurring in the regeneration of a lizard tail will provide clues for a therapeutic alternative to tissue injury. The present review provides an overview of aspects of rapid wound healing and roles of antibacterial peptides, effects of leukocytes on the tail regeneration, self-blocking of the inflammatory activation in leukocytes, as well as inflammatory resistance of blastemal cells or immature somatic cells during lizard tail regeneration. These mechanistic insights of self-control of inflammation during lizard tail regeneration may lead in the future to the development of therapeutic strategies to fight injury-induced inflammation.

Antibacterial Peptides Resistance in Staphylococcus aureus: Various Mechanisms and the Association with Pathogenicity

Staphylococcus aureus is a bacterium that mainly colonizes the nasal cavity and skin. To colonize the host, it is necessary for S. aureus to resist many antibacterial factors derived from human and commensal bacteria. Among them are the bacteria-derived antimicrobial peptides (AMPs) called bacteriocins. It was reported that some two-component systems (TCSs), which are signal transduction systems specific to bacteria, are involved in the resistance to several bacteriocins in S. aureus. However, the TCS-mediated resistance is limited to relatively low concentrations of bacteriocins, while high concentrations of bacteriocins still exhibit antibacterial activity against S. aureus. To determine whether we could obtain highly bacteriocin-resistant mutants, we tried to isolate highly nisin A-resistant mutants by exposing the cells to sub-minimum inhibitory concentrations (MICs) of nisin A. Nisin A is one of the bacteriocins produced by Lactococcus lactis and is utilized as a food preservative worldwide. Finally, we obtained highly nisin A-resistant mutants with mutations in one TCS, BraRS, and in PmtR, which is involved in the expression of pmtABCD. Notably, some highly resistant strains also showed increased pathogenicity. Based on our findings, this review provides up-to-date information on the role of TCSs in the susceptibility to antibacterial peptides. Additionally, the mechanism for high antimicrobial peptides resistance and its association with pathogenicity in S. aureus is elucidated.

Rational design of hyperstable antibacterial peptides for food preservation

We describe the design of peptides with properties like thermostability, pH stability, and antibacterial activity against a few bacterial food pathogens. Insights obtained from classical structure-function analysis of natural peptides and their mutants through antimicrobial and enzymatic assays are used to rationally develop a set of peptides. pH and thermostability assays were performed to demonstrate robust antimicrobial activity post-treatment with high temperatures and at wide pH ranges. We have also investigated the mode of action of these hyperstable peptides using membrane permeability assays, electron microscopy, and molecular dynamics simulations. Notably, through mutational studies, we show that these peptides elicit their antibacterial action via both membrane destabilization and inhibition of intracellular trypsin—the two functions attributable to separate peptide segments. Finally, toxicity studies and food preservation assays demonstrate the safety and efficacy of the designed peptides for food preservation. Overall, the study provides a general ‘blueprint’ for the development of stable antimicrobial peptides (AMPs). Insights obtained from this work may also be combined with combinatorial methods in high-throughput studies for future development of antimicrobials for various applications.

Roles of active forms of vitamin D in supporting innate immune systems and in reducing excess inflammation in COVID-19

A reduced supply of micronutrient vitamin D leads to a more severe course of coronavirus infection (COVID-19). Vitamin D deficiency is combined with a decrease in innate antiviral immunity and excess of inflammation. Vitamin D supplementation stimulates the synthesis of antibacterial peptides and is important for weakening the cytokine storm, reducing excessive acute and chronic inflammation, and also for compensating for chronic comorbid pathologies. Active forms of vitamin D (alfacalcidol, etc.) are of particular importance for compensating for vitamin D deficiency in elderly patients, endocrine-immune dysfunction, sarcopenia, chronic renal failure (in which the metabolism of vitamin D in the kidneys is disturbed).