Newly designed antimicrobial peptides with potent bioactivity and enhanced cell selectivity prevent and reverse rifampin resistance in Gram-negative bacteria

Zhu, Ningyi; Zhong, Chao; Liu, Tianqi; Zhu, Yuewen; Gou, Sanhu; Bao, Hexin; Yao, Jia; Ni, Jingman

doi:10.1016/j.ejps.2020.105665

Cited by 44 publications

(42 citation statements)

References 67 publications

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“…Notably, a combination of AMPs and antibiotics can be used to restore antibiotic sensitivity. Simultaneously, the bactericidal dosage of AMPs and antibiotics and the speed at which antibiotic resistance develops can be reduced with this combination, thereby highlighting the use of old antibiotics to avoid wastage of existing drug resources. , …”

Section: Introductionmentioning

confidence: 99%

“…Simultaneously, the bactericidal dosage of AMPs and antibiotics and the speed at which antibiotic resistance develops can be reduced with this combination, thereby highlighting the use of old antibiotics to avoid wastage of existing drug resources. 11,12 Anoplin (GLLKRIKTLL-NH 2 ) is a natural, short-chain AMP with an amphiphilic α-helical structure that is extracted from the venom of wasps (Anoplius samariensis). 13 It has unsatisfactory antimicrobial activity and low hemolytic activity.…”

Section: Introductionmentioning

confidence: 99%

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Novel Broad-Spectrum Antimicrobial Peptide Derived from Anoplin and Its Activity on Bacterial Pneumonia in Mice

Gou

Ouyang

et al. 2021

J. Med. Chem.

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The emergence of multidrug-resistant bacteria has major issues for treating bacterial pneumonia. Currently, anoplin (GLLKRIKTLL-NH 2 ) is a natural antimicrobial candidate derived from wasp venom. In this study, a series of new antimicrobial peptide (AMP) anoplin analogues were designed and synthesized. The relationship between their biological activities and their positive charge, hydrophobicity, amphipathicity, and secondary structure are described. The characteristic shared by these peptides is that positively charged amino acids and hydrophobic amino acids are severally arranged on the hydrophilic and hydrophobic surface of the α-helix to form a completely amphiphilic structure. To achieve ideal AMPs, below the range of the threshold of the cytotoxicity and hemolytic activity, their charges and hydrophobicity were increased as much. Among the new analogues, A-21 (KWWKKWKKWW-NH 2 ) exhibited the greatest antimicrobial activity (geometric mean of minimum inhibitory concentrations = 4.76 μM) against all the tested bacterial strains, high bacterial cell selectivity in vitro, high effectiveness against bacterial pneumonia in mice infected with Klebsiella pneumoniae, and low toxicity in mice (LD 50 = 82.01 mg/kg). A-21 exhibited a potent bacterial membrane-damaging mechanism and lipopolysaccharide-binding ability. These data provide evidence that A-21 is a promising antimicrobial candidate for the treatment of bacterial pneumonia.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Novel Broad-Spectrum Antimicrobial Peptide Derived from Anoplin and Its Activity on Bacterial Pneumonia in Mice

Gou

Ouyang

et al. 2021

J. Med. Chem.

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“…The helical wheel plots and prediction of the 3D secondary structure indicated that the three peptides have different hydrophobic faces and helical patterns. The small temporins are inactive against most bacterial strains ( Simmaco et al, 1996 ), however, truncation of amino acids is widely applied for adjusting peptide physicochemical properties, including membrane affinity ( Feng et al, 2020 ; He et al, 2020 ; Zhu et al, 2020 ). According to previous studies, modification of temporins is always performed via amino acids alteration or terminal sequence addition ( Mangoni et al, 2011 ; Bezzerri et al, 2014 ; Xie et al, 2019 ), the rational truncation of selected amino acid residues is quite rare.…”

Section: Resultsmentioning

confidence: 99%

Bioevaluation and Targeted Modification of Temporin-FL From the Skin Secretion of Dark-Spotted Frog (Pelophylax nigromaculatus)

Wang

Yang

et al. 2021

Front. Mol. Biosci.

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Bioactive proteins secreted by the granular glands of amphibian skin play a self-defensive role, and exhibit various bioactivities in vitro and in vivo. In light of the severity of the problem of antibiotic resistance for treating infections, many antimicrobial peptides (AMPs) have been developed and applied in clinical microbial treatments. We identified a naturally derived and potent antimicrobial peptide, temporin-FL, obtained from the skin secretion of Pelophylax nigromaculatus via “shotgun” cloning. Two truncated analogues of this peptide were chemically synthesized to explore their structural-functional relationships. The results of a functional evaluation showed that all of the tested AMPs were active against Gram-positive bacteria and fungi and demonstrated antibiofilm activity against methicillin-resistant Staphylococcus aureus (MRSA) but did not have an effect on Gram-negative bacteria. Moreover, temporin-FLa demonstrated a higher level of hydrophobicity and enhanced antimicrobial efficiency, as well as hemolytic activity and cell cytotoxicity than the parent peptide. Temporin-FLb, which evidenced significantly less α-helicity, was less potent against various microbes but exhibited lower cytotoxicity relating to mammalian cells. Both of the synthesized analogues possessed a higher therapeutic index than the original peptide. Moreover, the membrane permeability assay and the measuring membrane depolarization assay declared that temporin-FL and its analogues induced membrane fracture and depolarization; the quantitative biofilm formation assay and the observations of MRSA biofilms using scanning electron microscopy revealed that the AMPs caused biofilm disruption and blocked biofilm formation, the former experiments all confirming their antimicrobial and antibiofilm properties. Hence, the optimization of temporin-FL offers insights for the discovery of new drugs for treating MRSA infections.

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“…In particular, the analog L 1 GA 5 K exhibited a strong antimicrobial activity against rifampin-resistant E. coli (RRE) and high selectivity. It could prevent the emergence of rifampin resistance in Enterobacter, but also reverse rifampin resistance in RRE when used in combination with rifampin (Zhu et al, 2021).…”

Section: Antimicrobial Activitymentioning

confidence: 99%

Mastoparans: A Group of Multifunctional α-Helical Peptides With Promising Therapeutic Properties

Santana

Júnior

Fontes

et al. 2022

Front. Mol. Biosci.

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Biologically active peptides have been attracting increasing attention, whether to improve the understanding of their mechanisms of action or in the search for new therapeutic drugs. Wasp venoms have been explored as a remarkable source for these molecules. In this review, the main findings on the group of wasp linear cationic α-helical peptides called mastoparans were discussed. These compounds have a wide variety of biological effects, including mast cell degranulation, activation of protein G, phospholipase A2, C, and D activation, serotonin and insulin release, and antimicrobial, hemolytic, and anticancer activities, which could lead to the development of new therapeutic agents.

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Newly designed antimicrobial peptides with potent bioactivity and enhanced cell selectivity prevent and reverse rifampin resistance in Gram-negative bacteria

Cited by 44 publications

References 67 publications

Novel Broad-Spectrum Antimicrobial Peptide Derived from Anoplin and Its Activity on Bacterial Pneumonia in Mice

Novel Broad-Spectrum Antimicrobial Peptide Derived from Anoplin and Its Activity on Bacterial Pneumonia in Mice

Bioevaluation and Targeted Modification of Temporin-FL From the Skin Secretion of Dark-Spotted Frog (Pelophylax nigromaculatus)

Mastoparans: A Group of Multifunctional α-Helical Peptides With Promising Therapeutic Properties

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