Enhanced Activity against Multidrug-Resistant Bacteria through Coapplication of an Analogue of Tachyplesin I and an Inhibitor of the QseC/B Signaling Pathway

Yu, Rilei; Wang, Jiayi; So, Lok Yan; Harvey, Peta J.; Shi, Juan; Liang, Jiazhen; Dou, Qin; Li, Xiao; Yan, Xiayi; Huang, Yen‐Hua; Xu, Qingliang; Kaas, Quentin; Chow, Ho Yin; Wong, Kwok Yin; Craik, David J.; Zhang, Xiao Hua; Jiang, Tao; Wang, Yan

doi:10.1021/acs.jmedchem.9b01563

Cited by 20 publications

(14 citation statements)

References 47 publications

(89 reference statements)

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“…Tachyplesin I (TPI, 60 ) is a 14-amino acid β-hairpin anti-microbial peptide with two disulfide bonds originally isolated from the hepatocytes of Tachypleus tridentatus [ 70 ]. Replacement of all L-amino acids with D-amino acids in TPI generated TPAD ( 61 ) which retained the anti-microbial activity (MIC values about 8 μg/mL against P. aeruginosa ) and showed improved enzymatic stability as well as decreased hemolytic activity [ 71 ]. Mechanism study revealed that the activation of the quorum sensing E. coli regulators B and C (QseC/B) two-component system induced the bacterial resistance to peptide 61 , while the combination of 61 with QseC/B inhibitor obviously increased the bactericidal effect against several multidrug-resistant bacteria.…”

Section: Emerging Mnps As Promising Antibiotics For Inhibiting ...mentioning

confidence: 99%

Discovery of Marine Natural Products as Promising Antibiotics against Pseudomonas aeruginosa

Maimaitiming

Zhou

et al. 2022

Marine Drugs

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Pseudomonas aeruginosa, one of the most intractable Gram-negative bacteria, has become a public health threat due to its outer polysaccharide layer, efflux transporter system, and high level of biofilm formation, all of which contribute to multi-drug resistance. Even though it is a pathogen of the highest concern, the status of the antibiotic development pipeline is unsatisfactory. In this review, we summarize marine natural products (MNPs) isolated from marine plants, animals, and microorganisms which possess unique structures and promising antibiotic activities against P. aeruginosa. In the last decade, nearly 80 such MNPs, ranging from polyketides to alkaloids, peptides, and terpenoids, have been discovered. Representative compounds exhibited impressive in vitro anti-P. aeruginosa activities with MIC values in the single-digit nanomolar range and in vivo efficacy in infectious mouse models. For some of the compounds, the preliminary structure-activity-relationship (SAR) and anti-bacterial mechanisms of selected compounds were introduced. Compounds that can disrupt biofilm formation or membrane integrity displayed potent inhibition of multi-resistant clinical P. aeruginosa isolates and could be considered as lead compounds for future development. Challenges on how to translate hits into useful candidates for clinical development are also proposed and discussed.

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Section: Emerging Mnps As Promising Antibiotics For Inhibiting ...mentioning

confidence: 99%

Discovery of Marine Natural Products as Promising Antibiotics against Pseudomonas aeruginosa

Maimaitiming

Zhou

et al. 2022

Marine Drugs

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“…Tachyplesin I, from the hemocytes of the horseshoe crab Tachypleus tridentatus , [ 139 ] has broad antimicrobial activity against Gram‐positive and Gram‐negative bacteria, [ 140,142,157–159 ] as well as anti‐fungal, [ 140 ] anti‐viral [ 160 ] and anti‐cancer activity. [ 142,161 ] Despite its antimicrobial activity, the toxicity of tachyplesin I toward mammalian cells limits its clinical application.…”

Section: Antimicrobial Cpps To Target Drug‐resistant Bacteria Inside ...mentioning

confidence: 99%

Antimicrobial peptides provide wider coverage for targeting drug‐resistant bacterial pathogens

2021

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We need new treatment options to control bacterial infections. Bacteria use several strategies to resist drug treatment, including modification of the drug target, and adaptation to a different lifestyle, such as intracellular niches within host cells. Drugs that act on diverse targets are less likely to induce resistance in bacteria, than current antibiotics acting on a single molecular target. Antimicrobial peptides have been explored as a new class of antibiotics because they selectively kill bacteria via a mechanism that involves recognition of the negatively charged microbial surface. Furthermore, antimicrobial peptides with cell‐penetrating properties can cross host cell membranes and target bacteria in the cytosol or sequestered in vesicles. Therefore, bacteria in intracellular niches are less capable of evading treatment and the likelihood of establishing drug resistance is further reduced. This review highlights the potential of antimicrobial peptides as alternative therapeutics to target bacterial pathogens in both extracellular and intracellular environments, and to avoid acquired drug‐resistance.

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“…Wang et al. synthesized all D‐amino acid‐modified Tachyplesin‐1 which exhibits decreased hemolytic activity and enhanced stability compared to the unmodified Tachyplesin‐1 . Moreover, the D‐amino acid‐modified Tachyplesin‐1 showed comparable antibacterial activity including drug‐resistant bacteria.…”

Section: β‐Hairpin Antimicrobial Peptidesmentioning

confidence: 99%

Cationic Amphiphilic Peptides: Synthetic Antimicrobial Agents Inspired by Nature

Kundu

2020

ChemMedChem

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Antimicrobial peptides are ubiquitous in multicellular organisms and have served as defense mechanisms for their successful evolution and throughout their life cycle. These peptides are short cationic amphiphilic polypeptides of fewer than 50 amino acids containing either a few disulfide-linked cysteine residues with a characteristic β-sheet-rich structure or linear α-helical conformations with hydrophilic side chains at one side of the helix and hydrophobic side chains on the other side. Antimicrobial peptides cause bacterial cell lysis either by direct cellsurface damage via electrostatic interactions between the cationic side chains of the peptide and the negatively charged cell surface, or by indirect modulation of the host defense systems. Electrostatic interactions lead to bacterial cell membrane disruption followed by leakage of cellular components and finally bacterial cell death. Because of their unusual mechanism of cell damage, antimicrobial peptides are effective against drug-resistant bacteria and may therefore prove more effective than classical antibiotics in certain cases. Currently, around 3000 natural antimicrobial peptides from six kingdoms (bacteria, archaea, protists, fungi, plants, and animals) have been isolated and sequenced. However, only a few of them are under clinical trials and/or in the commercial development stage for the treatment of bacterial infections caused by antibiotic-resistant bacteria. Moreover, high structural complexity, poor pharmacokinetic properties, and low antibacterial activity of natural antimicrobial peptides hinder their progress in drug development. To overcome these hurdles, researchers have become increasingly interested in modification and nature-inspired synthetic antimicrobial peptides. This review discusses some of the recent studies reported on antimicrobial peptides.

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Enhanced Activity against Multidrug-Resistant Bacteria through Coapplication of an Analogue of Tachyplesin I and an Inhibitor of the QseC/B Signaling Pathway

Cited by 20 publications

References 47 publications

Discovery of Marine Natural Products as Promising Antibiotics against Pseudomonas aeruginosa

Discovery of Marine Natural Products as Promising Antibiotics against Pseudomonas aeruginosa

Antimicrobial peptides provide wider coverage for targeting drug‐resistant bacterial pathogens

Cationic Amphiphilic Peptides: Synthetic Antimicrobial Agents Inspired by Nature

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