Targeted and Intracellular Antibacterial Activity against S. agalactiae of the Chimeric Peptides Based on Pheromone and Cell-Penetrating Peptides

Abstract

The significance of the complex bacterial ecosystem in the human body and the impediment of the mammalian membrane against many antibiotics together emphasize the necessity to develop antimicrobial agents with precise antimicrobial and cell-penetrating activities. A simple and feasible method for generating dual-function antimicrobial peptides inspired by highly hydrophobic peptide pheromone and cationic cell-penetrating peptides is presented. Furthermore, the extension of the peptide candidate library is achieved by modifying the charged domain. The bacteria-selective peptides L1, L2, L10, and L11 kill Streptococcus agalactiae by disrupting the membrane structure, and the targeted mechanism is suggested where the peptides offset the entrapment of S. agalactiae rather than of other bacteria. Moreover, L2 and L10 possess intracellular antibacterial activity and carrier property, which is mainly dependent on endocytosis. Given their suitable biocompatibility, high tolerance, no drug resistance, and effective antimicrobial capacity in a mouse mastitis model, L2 and L10 can be powerful weapons against S. agalactiae pathogen infection.

De novo design of a pH-triggered self-assembled β-hairpin nanopeptide with the dual biological functions for antibacterial and entrapment

“…Acid tolerance of enteric pathogens such as Escherichia coli and Salmonella plays an important role in evading the acid barrier of the stomach (pH 1.5–2.5) and small intestine (pH 4.0–6.0), leading to bacterial colonization and infection in the intestinal tract, which results in bacterial gastroenteritis and causes a range of symptoms, including vomiting, severe abdominal cramps and diarrhea [ 1 ]. However, it is widely accepted that antibiotic therapy is not the best therapeutic strategy for enteric infection due to the increased drug- resistance of bacteria and disruption of microbial communities as a consequence of broad-spectrum therapy [ 2 , 3 ]. Inspired by the above, an acid-triggered antibacterial treatment strategy might be developed to target specific acid resistance to reduce side effects and avoid secondary infections [ 4 ].…”

Effect and Mechanisms of Antibacterial Peptide Fraction from Mucus of C. aspersum against Escherichia coli NBIMCC 8785

“…In infections in an advanced-phase 48 h bacterial culture, it was effective to apply a 50% peptide fraction. Using this concentration for a short time of 1 h, a strong inhibiting effect on the bacterial cells was registered, represented by major damage to the cells' surface layers [5,9,[47][48][49][50]52,64]. In the bacterial infections in an initial phase (18 h bacterial culture), a 50% peptide fraction with one-hour impact lead to an almost 100% inhibition of the structures and functions of the E. coli NBIMCC 8785.…”

The Trp-rich Antimicrobial Amphiphiles With Intramolecular Aromatic Interactions for the Treatment of Bacterial Infection

“…The MTT (3-[4,5 dimethylthiozol-2-yl]-2,5-diphenylterazoliumbromide) dye was selected to analyze the cytotoxicity of peptides against the murine macrophage cell RAW 264.7 (National Collection of Authenticated Cell Cultures, Shanghai, China), human embryonic kidneys (HK293T), and the porcine intestinal epithelial cells (IPEC-J2) as in our previously study ( Li et al, 2020 ). In short, the cells (10 4 cells/well) were seeded into 96-well plates and were cultivated overnight.…”