In Vitro Pharmacodynamics and Bactericidal Mechanism of Fungal Defensin-Derived Peptides NZX and P2 against Streptococcus agalactiae

Abstract

(1) Background: Based on the hazard of Streptococcus agalactiae to human and animal health and the increasing drug resistance, it is urgent to develop new antimicrobial agents with high bactericidal activity and low drug resistance against S. agalactiae. This study aims to investigate in vitro pharmacodynamics and bactericidal mechanism of fungal defensin-derived peptides NZX and P2 against S. agalactiae. (2) Methods: Minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) were determined by broth dilution method and AGAR plate dilution method. Cell membrane integrity was determined by flow cytometer. Cell morphological changes were observed by scanning electron microscope (SEM) and transmission electron microscope (TEM). (3) Results: MIC values (NZX: 0.11 μM, P2: 0.91 μM) and MPC (NZX: 1.82 μM) showed their higher antibacterial activity and stronger inhibition ability of drug resistance mutation. The bactericidal mechanism was elucidated that P2 caused S. agalactiae ACCC 61733 cells to deform, bound to the cell wall, and perturbed cell membrane, resulting in K+ leakage, membrane hyperpolarization, ATP release, and reduced cell contents. Compared with P2, NZX focuses on the cell wall, and it bound to the cell wall causing cells boundary disappearance. (4) Conclusion: NZX and P2 are promising antimicrobial agents for streptococcicosis treatment.

Editorial: Community series in antimicrobial peptides: Molecular design, structure function relationship and biosynthesis optimization

“…In multicellular organisms AMPs are part of innate immunity and thus serve as the first line of defense against pathogens. Compared to traditional antimicrobials, AMPs are characterized by more narrow mutant selection windows and lesser chances of emergence of bacterial resistance (Rodríguez-Rojas et al, 2014 , 2018 ; Yu et al, 2018 ; Liu et al, 2021 ; Zheng et al, 2021 ; Wu et al, 2022 ). Activities of AMPs are usually evaluated in vitro with exponentially growing bacteria, but under natural conditions, bacterial growth rates are much slower (Savageau, 1983 ; Spaulding et al, 2017 ).…”

Plectasin: from evolution to truncation, expression, and better druggability

“…Phosphate-buffered saline (PBS) was used as a negative control, and vancomycin was used as a positive control. The calculation formula for the Post-antibiotic effect (PAE) was based on previous study (Wu et al, 2022).…”

Molecular Modification of Kex2 P1’ Site Enhances Expression and Druggability of Fungal Defensin

“…Plectasin is derived from the saprophytic ascus fungus ( Pseudoplectania nigrella ) as the first AMP fungal defensin with a typical CSαβ structure [ 16 ] and with a good bactericidal effect against G + bacteria by binding with cell wall component lipid II [ 17 ]. There is a good preliminary foundation in our team regarding the modification, expression, and efficacy studies of this class of antimicrobial peptides, which are expected to have good development prospects for antibiotic substitution and combination administration to hinder drug resistance [ 18 , 19 , 20 , 21 , 22 , 23 ]. We know that defensins take over half of AMPs in quantity from the AMP databases [ 24 , 25 ].…”