Role of membrane proteins in bacterial resistance to antimicrobial peptides

Vimberg, Vladimir; Buriánková, Karolína; Mazumdar, Aninda; Branný, Pavel; Novotná, Gabriela Balíková

doi:10.1002/med.21869

Cited by 6 publications

(3 citation statements)

References 69 publications

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“…This clinically isolated strain carried two well-characterized mutations in gyrA (S83L and D87N) causing a high-level fluoroquinolone resistance, as well as a higher-than-normal spontaneous mutation rate [ 19 ]. Approved by WHO as the main drug for the treatment various infections caused by Cram-negative bacteria including multidrug-resistance strains, polymyxin B was taken as the reference agent [ 20 ]. This experiment indicated that abarenicins induced a low-level stable resistance of E. coli with MICs up to 4-fold (for Ap11) and 8-fold (for Ap9) higher than those of the wild-type strain.…”

Section: Resultsmentioning

confidence: 99%

Novel β-Hairpin Peptide from Marine Polychaeta with a High Efficacy against Gram-Negative Pathogens

et al. 2022

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In recent years, new antibiotics targeting multidrug resistant Gram-negative bacteria have become urgently needed. Therefore, antimicrobial peptides are considered to be a novel perspective class of antibacterial agents. In this study, a panel of novel BRICHOS-related β-hairpin antimicrobial peptides were identified in transcriptomes of marine polychaeta species. Two of them—abarenicin from Abarenicola pacifica and UuBRI-21 from Urechis unicinctus—possess strong antibacterial potential in vitro against a wide panel of Gram-negative bacteria including drug-resistant strains. Mechanism of action assays demonstrate that peptides disrupt bacterial and mammalian membrane integrity. Considering the stronger antibacterial potential and a low ability of abarenicin to be bound by components of serum, this peptide was selected for further modification. We conducted an alanine and arginine scanning of abarenicin by replacing individual amino acids and modulating hydrophobicity so as to improve its antibacterial potency and membrane selectivity. This design approach allowed us to obtain the Ap9 analog displaying a high efficacy in vivo in the mice septicemia and neutropenic mice peritonitis models. We demonstrated that abarenicin analogs did not significantly induce bacterial resistance after a four-week selection experiment and acted on different steps of the biofilm formation: (a) killing bacteria at their planktonic stage and preventing biofilm formation and (b) degrading pre-formed biofilm and killing embedded bacteria. The potent antibacterial and antibiofilm activity of the abarenicin analog Ap9 with its high efficacy in vivo against Gram-negative infection in mice models makes this peptide an attractive candidate for further preclinical investigation.

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Section: Resultsmentioning

confidence: 99%

Novel β-Hairpin Peptide from Marine Polychaeta with a High Efficacy against Gram-Negative Pathogens

et al. 2022

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“…[ 1 ] The SARS‐CoV‐2 pandemic has resulted in an increased usage of all antibiotics, further exacerbating the risks of bacterial resistance. [ 2 ] Therefore, in recent years, the crisis of multidrug‐resistant bacteria caused by antibiotic resistance has plagued human health and animal husbandry. [ 3 ] In addition, the Chinese government has issued the policy to ban the addition of feed antibiotics in feed and breeding from July 1, 2020, which has led to a significant increase in the demand for antibiotic substitutes in feed.…”

Section: Introductionmentioning

confidence: 99%

Designing Self‐Assembling Chimeric Peptide Nanoparticles with High Stability for Combating Piglet Bacterial Infections

Tan

Tang

et al. 2022

Advanced Science

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As a novel type of antibiotic alternative, peptide‐based antibacterial drug shows potential application prospects attributable to their unique mechanism for lysing the membrane of pathogenic bacteria. However, peptide‐based antibacterial drugs suffer from a series of problems, most notably their immature stability, which seriously hinders their application. In this study, self‐assembling chimeric peptide nanoparticles (which offer excellent stability in the presence of proteases and salts) are constructed and applied to the treatment of bacterial infections. In vitro studies are used to demonstrate that peptide nanoparticles NPs1 and NPs2 offer broad‐spectrum antibacterial activity and desirable biocompatibility, and they retain their antibacterial ability in physiological salt environments. Peptide nanoparticles NPs1 and NPs2 can resist degradation under high concentrations of proteases. In vivo studies illustrate that the toxicity caused by peptide nanoparticles NPs1 and NPs2 is negligible, and these nanoparticles can alleviate systemic bacterial infections in mice and piglets. The membrane permeation mechanism and interference with the cell cycle differ from that of antibiotics and mean that the nanoparticles are at a lower risk of inducing drug resistance. Collectively, these advances may accelerate the development of peptide‐based antibacterial nanomaterials and can be applied to the construction of supramolecular nanomaterials.

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“…Antimicrobial peptides are molecules made up of amino acids produced by the body, they are an important part of the body's immune system (Vimberg et al, 2022). Peptides have low molecular weight, broad antibacterial spectrum, and endurance to resistance (Lin et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

The Effect of Oral Administration of the Antibacterial Peptide MPX on Intestinal Inflammation of Mice in Experimental Infection with Escherichia Coli Strain O157: H7

Zhao

Fotina

Фотіна

et al. 2022

Scientific Horizons

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Escherichia coli is a gram-negative bacterium, an intestinal pathogen that can cause intestinal inflammation. Antimicrobial peptides are a class of small molecule peptides, which has good antibacterial activity against a variety of gram-positive and negative bacteria. In this regard, the authors aimed to study the effect of the antimicrobial peptide MPX, which was administered orally, on the intestinal wall of mice infected with the intestinal barrier function, which were infected with E. coli. Synthesis and purification of the antimicrobial peptide MPX (H-INWKGIAAMAKKLL-NH2) was performed by Jier Sheng Hua (Shanghai, China). Mass spectrometry and liquid chromatography (HPLC) were used for this purpose. Escherichia Coli (O157: H7 ATCC43889) was isolated from human faeces in which haemolytic uremic syndrome was reported. Solid LB agar (Solarbio, China) was used to isolate enterohemorrhagic E. coli. The culture was obtained from the Chinese Institute of Veterinary Drug Control (Beijing, China). The results of necropsy found that using of an orally administered MPX could alleviate the damage of E. coli to the liver, spleen, and the lungs were less affected. According to H&E results in case of an orally administered MPX group considerably relieved duodenum and organs on day 7 and day 28. qRT-PCR results showed orally administered MPX could reduce the inflammation-related factors in the mRNA expression of IL-2 and IL-6 and TNF-α on day 7 and day 28. In addition, orally administered MPX could significantly increase them RNA expression of tight junction proteins Occludin and Zo-1 on day 7 and day 28. The results of immune histochemistry further showed that an orally administered MPX could increase the mRNA expression of MUC2 in jejunum. The above results showed that orally administered MPX could alleviate the attack of E. coli on the intestinal tract of mice, relieve intestinal inflammation, and improve the intestinal barrier function. This study lays a theoretical foundation for adding antimicrobial peptides to food. In orally administered MPX authors can see reducing the mRNA expression of inflammation-related factors, thereby alleviating the intestinal inflammation caused by E. coli infection in mice. Authors can add that orally administered MPX shows an increase in mRNA expression of tight junction protein in intestines and improves the intestinal barrier function. This study lays the foundation for adding antimicrobial peptides to food to relieve inflammation and improve barrier function in clinical practices

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Role of membrane proteins in bacterial resistance to antimicrobial peptides

Cited by 6 publications

References 69 publications

Novel β-Hairpin Peptide from Marine Polychaeta with a High Efficacy against Gram-Negative Pathogens

Novel β-Hairpin Peptide from Marine Polychaeta with a High Efficacy against Gram-Negative Pathogens

Designing Self‐Assembling Chimeric Peptide Nanoparticles with High Stability for Combating Piglet Bacterial Infections

The Effect of Oral Administration of the Antibacterial Peptide MPX on Intestinal Inflammation of Mice in Experimental Infection with Escherichia Coli Strain O157: H7

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