In-depth biological characterization of two black soldier fly anti- Pseudomonas peptides reveals LPS-binding and immunomodulating effects

Abstract

As effector molecules of the innate immune system, antimicrobial peptides (AMPs) have gathered substantial interest as a potential future generation of antibiotics. Here, we demonstrate the anti- Pseudomonas activity and lipopolysaccharide (LPS)-binding ability of HC1 and HC10, two cecropin peptides from the black soldier fly ( Hermetia Illucens ). Both peptides are active against a wide range of Pseudomonas aeruginosa strains, including drug-resistant clinical isolates. Moreover, HC1 and HC10 can bind to lipid A, the toxic center of LPS and reduce the LPS-induced nitric oxide and cytokine production in murine macrophage cells. This suggests that the peptide-LPS binding can also lower the strong inflammatory response associated with P. aeruginosa infections. As the activity of AMPs is often influenced by the presence of salts, we studied the LPS-binding activity of HC1 and HC10 in physiological salt concentrations, revealing a strong decrease in activity. Our research confirmed the early potential of HC1 and HC10 as starting points for anti- Pseudomonas drugs, as well as the need for structural or formulation optimization before further preclinical development can be considered. IMPORTANCE The high mortality and morbidity associated with Pseudomonas aeruginosa infections remain an ongoing challenge in clinical practice that requires urgent action. P. aeruginosa mostly infects immunocompromised individuals, and its prevalence is especially high in urgent care hospital settings. Lipopolysaccharides (LPSs) are outer membrane structures that are responsible for inducing the innate immune cascade upon infection. P. aeruginosa LPS can cause local excessive inflammation, or spread systemically throughout the body, leading to multi-organ failure and septic shock. As antimicrobial resistance rates in P. aeruginosa infections are rising, the research and development of new antimicrobial agents remain indispensable. Especially, antimicrobials that can both kill the bacteria themselves and neutralize their toxins are of great interest in P. aeruginosa research to develop as the next generation of drugs.

The Effect of Dietary Protein Hydrolysate from Black Soldier Fly Larvae and Schizochytrium on Palatability, Nutrient Metabolites and Health Status in Beagle Dogs

“…The dietary supplementation of 5%, 10%, and 15% BSFPs could significantly reduce the concentration of IL-8 in the plasma of dogs. Research have shown that the anti-inflammatory activity of BSFL oil alleviated dextran sulfate sodium (DSS)-induced colitis by modulating Toll-like receptor (TLR) signaling [ 50 ], and the antimicrobial peptides (AMPs) from BSFL reduced LPS-induced nitric oxide and cytokine production in murine macrophage cells [ 51 ]. Furthermore, protein hydrolysate from black soldier fly larvae (BSFP), like other enzymatically hydrolyzed proteins from edible insects, might have anti-inflammatory capacity [ 52 ].…”

Influence of a Mixture of Protein Hydrolysate from Black Soldier Fly Larvae and Schizochytrium on Palatability, Plasma Biochemistry, and Antioxidative and Anti-Inflammatory Capacity in Cat Diets

“…In addition, adding 15% lyophilized microalgae powder from schizochytrium in the diet can maintain a normal physiological state of the intestine by downregulating the gene expression level of pro-inflammatory cytokines (IL-6, IL-8, and IL-1β) in zebrafish [ 60 ]. A similar effect exists in black soldier fly larvae as black soldier fly larvae played an anti-inflammatory function by downregulating the IL-8 and IL-1β gene expressions and mediating the mechanism of toll-like receptors (TLR) signaling [ 61 ], and the antimicrobial peptides (AMPs) from black soldier fly larvae reduced the LPS-induced nitric oxide and cytokine production in murine macrophage cells [ 62 ]. Additionally, the protein hydrolysate from black soldier fly larvae also may have anti-inflammatory activity, as other enzymatically hydrolyzed proteins of edible insects [ 8 ].…”