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Rapid Membrane-Penetrating Hybrid Peptides Achieve Efficient Dual Antimicrobial and Antibiofilm Activity through a Triple Bactericidal Mechanism.

ABSTRACT: Antimicrobial peptides (AMPs) are a type of biomaterial used against multidrug resistant (MDR) bacteria. This study reports the design of a peptide family rich in tryptophan and lysine obtained by optimizing a natural AMP using single factor modification and pheromone hybridization to expedite the penetration and improve the antimicrobial activity of AMPs. S-4, L-4, and P-4 showed α-helical structures, exhibited extremely fast membrane penetration rates in vitro, and could kill MDR bacteria efficiently within 30 min. Intracellular fluorescence localization suggested rapid membrane-penetrating of AMPs within 1 min, making it more difficult for bacteria to develop resistance. Furthermore, they could effectively inhibit and destroy bacterial biofilms with dual antimicrobial and antibiofilm activity. In the treatment of skin infections caused by MDR-Acinetobacter baumannii in vivo , AMPs could effectively alleviate inflammation without toxic side effects. Additionally, the triple antimicrobial damage of AMPs was described in detail. AMPs rapidly penetrate the cell membrane, inducing cell membrane damage, triggering oxidative damage with a storm of reactive oxygen species and leading to bacterial death through leakage of cellular contents by complexing with DNA. The multiple damage is an important means by which AMPs can prevent bacterial resistance adequately.

SUBMITTER: Liu Y

PROVIDER: S-EPMC11191078 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature

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Rapid Membrane-Penetrating Hybrid Peptides Achieve Efficient Dual Antimicrobial and Antibiofilm Activity through a Triple Bactericidal Mechanism.

Liu Yifan Y Cui Pengfei P Tan Rong R Ru Shaoguo S

ACS omega 20240605 24

Antimicrobial peptides (AMPs) are a type of biomaterial used against multidrug resistant (MDR) bacteria. This study reports the design of a peptide family rich in tryptophan and lysine obtained by optimizing a natural AMP using single factor modification and pheromone hybridization to expedite the penetration and improve the antimicrobial activity of AMPs. S-4, L-4, and P-4 showed α-helical structures, exhibited extremely fast membrane penetration rates <i>in vitro</i>, and could kill MDR bacter ...[more]

PMID: 38911764

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Project description:Staphylococci, notably biofilm-forming Staphylococcus epidermidis, have been recognized as global nosocomial pathogens in medical device-related infections. Their potential to attach to and form biofilm on indwelling catheters are significant factors impeding conventional treatment. Due to their extensive antimicrobial and antibiofilm actions, antimicrobial peptides (AMPs) have attracted interest as promising alternative compounds for curing difficult-to-treat, biofilm-forming bacterial infections. Cecropin A-melittin or CM, a well-known hybrid peptide, exhibits broad-spectrum antimicrobial activity, however it also possesses high toxicity. In the current study, a series of hybrid CM derivatives was designed using an amino acid substitution strategy to explore potential antibacterial and antibiofilm peptides with low toxicity. Among the derivatives, CM-10K14K showed the least hemolysis along with potent antibacterial activity against biofilm-forming S. epidermidis (MICs = 3.91 μg/mL) and rapid killing after 15 min exposure (MBCs = 7.81 μg/mL). It can prevent the formation of S. epidermidis biofilm and also exhibited a dose-dependent eradication activity on mature or established S. epidermidis biofilm. In addition, it decreased the development of biofilm by surviving bacteria, and formation of biofilm on the surface of CM-10K14K-impregnated catheters. Released CM-10K14K decreased planktonic bacterial growth and inhibited biofilm formation by S. epidermidis in a dose-dependent manner for 6 and 24 h post-exposure. Impregnation of CM-10K14K prevented bacterial attachment on catheters and thus decreased formation of extensive biofilms. SEM images supported the antibiofilm activity of CM-10K14K. Flow cytometry analysis and TEM images demonstrated a membrane-active mechanism of CM-10K14K, inducing depolarization and permeabilization, and subsequent membrane rupture leading to cell death. The presence of an interaction with bacterial DNA was verified by gel retardation assay. These antibacterial and antibiofilm activities of CM-10K14K suggest its potential application to urinary catheters for prevention of biofilm-forming colonization or for treatment of medical devices infected with S. epidermidis.

Dataset Information

Rapid Membrane-Penetrating Hybrid Peptides Achieve Efficient Dual Antimicrobial and Antibiofilm Activity through a Triple Bactericidal Mechanism.

Publications

Rapid Membrane-Penetrating Hybrid Peptides Achieve Efficient Dual Antimicrobial and Antibiofilm Activity through a Triple Bactericidal Mechanism.

Similar Datasets

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