Mechanisms and consequences of bacterial resistance to antimicrobial peptides

Drug Resistance Updates, Journal Year: 2016, Volume and Issue: 26, P. 43 - 57

Published: April 30, 2016

Cationic antimicrobial peptides (AMPs) are an intrinsic part of the human innate immune system. Over 100 different AMPs known to exhibit broad-spectrum antibacterial activity. Because increased frequency resistance conventional antibiotics there is interest in developing as alternative therapy. Several cationic that derivatives from system currently clinical development. There also ongoing studies aimed at modulating expression boost response. In this review we discuss potential problems associated with these therapeutic approaches. considerable experimental data describing mechanisms by which bacteria can develop AMPs. As for any type drug resistance, rate AMP would emerge and spread a population natural setting will be determined complex interplay several factors, including mutation supply rate, fitness resistant mutant concentrations, strength selective pressure. have already shown AMP-resistant bacterial mutants display broad cross-resistance variety structures modes action. Therefore, routine administration treat infections may select pathogens capable better evading The ramifications levels exposure on development pathogenesis not yet understood. This something needs carefully studied monitored if used settings.

Language: Английский

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Antimicrobial Peptides: Mechanisms of Action and Resistance

Journal of Dental Research, Journal Year: 2016, Volume and Issue: 96(3), P. 254 - 260

Published: Nov. 22, 2016

More than 40 antimicrobial peptides and proteins (AMPs) are expressed in the oral cavity. These AMPs have been organized into 6 functional groups, 1 of which, cationic AMPs, has received extensive attention recent years for their promise as potential antibiotics. The goal this review is to describe advances our understanding diverse mechanisms action bacterial resistance against these peptides. recently developed peptide GL13K used an example illustrate many discussed concepts. Cationic typically exhibit amphipathic conformation, which allows increased interaction with negatively charged membranes. Peptides undergo changes conformation aggregation state presence membranes; conversely, lipid packing can adapt As a consequence, single act through several depending on peptide's structure, peptide:lipid ratio, properties membrane. Accumulating evidence shows that addition acting at cell membrane, may wall, inhibit protein folding or enzyme activity, intracellularly. Therefore, once reached its internal target, difference mechanism gram-negative gram-positive bacteria be less pronounced formerly assumed. While should not cause widespread due preferential attack cases where specific targets involved, possibility exists genetic mutations resistance. Indeed, clinical use raised concern therapeutic could associated endogenous host-defense Current suggests rare event overcome by subtle structural modifications AMP.

Language: Английский

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Alternatives to Conventional Antibiotics in the Era of Antimicrobial Resistance

Trends in Microbiology, Journal Year: 2019, Volume and Issue: 27(4), P. 323 - 338

Published: Jan. 24, 2019

Language: Английский

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The multifaceted nature of antimicrobial peptides: current synthetic chemistry approaches and future directions

Chemical Society Reviews, Journal Year: 2021, Volume and Issue: 50(13), P. 7820 - 7880

Published: Jan. 1, 2021

This review discusses the diversity of structure and physicochemical properties antimicrobial peptides their derivatives, various chemical synthetic strategies that have been applied in development, how this links to activity.

Language: Английский

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Antibiotic Hybrids: the Next Generation of Agents and Adjuvants against Gram-Negative Pathogens?

Clinical Microbiology Reviews, Journal Year: 2018, Volume and Issue: 31(2)

Published: March 13, 2018

SUMMARY The global incidence of drug-resistant Gram-negative bacillary infections has been increasing, and there is a dire need to develop novel strategies overcome this problem. Intrinsic resistance in bacteria, such as their protective outer membrane constitutively overexpressed efflux pumps, major survival weapon that renders them refractory current antibiotics. Several potential avenues problem have at the heart antibiotic drug discovery past few decades. We review some these strategies, with emphasis on hybrids either stand-alone antibacterial agents or adjuvants potentiate primary bacteria. Antibiotic hybrid defined synthetic construct two more pharmacophores belonging an established agent known elicit desired antimicrobial effect. concepts, advances, challenges are elaborated article. Moreover, we discuss several were clinical evaluation. Mechanistic insights into how tobramycin-based able legacy antibiotics multidrug-resistant bacilli also highlighted. indeed promising future therapeutic strategy pathogens and/or expand usefulness our arsenal.

Language: Английский

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Recent Progress in Polymer Research to Tackle Infections and Antimicrobial Resistance

Biomacromolecules, Journal Year: 2018, Volume and Issue: 19(6), P. 1888 - 1917

Published: May 2, 2018

Global health is increasingly being threatened by the rapid emergence of drug-resistant microbes. The ability these microbes to form biofilms has further exacerbated scenario leading notorious infections that are almost impossible treat. For addressing this clinical threat, various antimicrobial polymers, polymer-based hydrogels and polymer-coated surfaces have been developed in recent past. This review aims discuss such strategies with a focus on their current advancement field. Antimicrobial whose designs inspired from peptides (AMPs), described an emphasis structure-activity analysis. Additionally, antibiofilm activity vivo efficacy delineated elucidate real potential polymers as possible therapeutics. hydrogels, prepared either inherently or biocide-loaded into polymer-derived hydrogel matrix, elaborated followed engineer surfaces. In end, challenges accentuated along future directions for expansion field toward tackling resistance.

Language: Английский

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Advances in Development of Antimicrobial Peptidomimetics as Potential Drugs

Molecules, Journal Year: 2017, Volume and Issue: 22(9), P. 1430 - 1430

Published: Aug. 29, 2017

The rapid emergence of multidrug-resistant pathogens has evolved into a global health problem as current treatment options are failing for infections caused by pan-resistant bacteria. Hence, novel antibiotics in high demand, and this reason antimicrobial peptides (AMPs) have attracted considerable interest, since they often show broad-spectrum activity, fast killing cell selectivity. However, the therapeutic potential natural AMPs is limited their short plasma half-life. Antimicrobial peptidomimetics mimic structure biological activity AMPs, but display extended stability presence matrices. In present review, focus on developments reported last decade with respect to design, synthesis, cytotoxic side effects well applications anti-infective agents. Specifically, only modular residues connected via amide linkages will be discussed. These comprise classes α-peptoids (N-alkylated glycine oligomers), β-peptoids β-alanine β3-peptides, α/β3-peptides, α-peptide/β-peptoid hybrids, α/γ N-acylated N-aminoethylpeptides (AApeptides), oligoacyllysines (OAKs). Such particular interest due potent versatile convenient optimization assembly standard solid-phase procedures.

Language: Английский

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Mini Review on Antimicrobial Peptides, Sources, Mechanism and Recent Applications

Protein and Peptide Letters, Journal Year: 2019, Volume and Issue: 27(1), P. 4 - 16

Published: Aug. 23, 2019

Antimicrobial peptides in recent years have gained increased interest among scientists, health professionals and the pharmaceutical companies owing to their therapeutic potential. These are low molecular weight proteins with broad range antimicrobial immuno modulatory activities against infectious bacteria (Gram positive Gram negative), viruses fungi. Inability of micro-organisms develop resistance most peptide has made them as an efficient product which can greatly impact new era antimicrobials. In addition this these also demonstrates efficacy, high specificity, decreased drug interaction, toxicity, biological diversity direct attacking properties. Pharmaceutical industries therefore conducting appropriate clinical trials potential drugs. More than 60 drugs already reached market several hundreds novel preclinical development. Rational designing be used further modify chemical physical properties existing peptides. This mini review will discuss sources, mechanism applications treatment diseases.

Language: Английский

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Chalcone derivatives and their antibacterial activities: Current development

Bioorganic Chemistry, Journal Year: 2019, Volume and Issue: 91, P. 103133 - 103133

Published: July 19, 2019

Language: Английский

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Selective Antimicrobial Activities and Action Mechanism of Micelles Self-Assembled by Cationic Oligomeric Surfactants

ACS Applied Materials & Interfaces, Journal Year: 2016, Volume and Issue: 8(6), P. 4242 - 4249

Published: Jan. 28, 2016

This work reports that cationic micelles formed by trimeric, tetrameric, and hexameric surfactants bearing amide moieties in spacers can efficiently kill Gram-negative E. coli with a very low minimum inhibitory concentration (1.70-0.93 μM), do not cause obvious toxicity to mammalian cells at the concentrations used. With increase of oligomerization degree, antibacterial activity oligomeric increases, i.e., surfactant > tetrameric trimeric surfactant. Isothermal titration microcalorimetry, scanning electron microscopy, zeta potential results reveal interact cell membrane through two processes. First, integrity outer is disrupted electrostatic interaction ammonium groups anionic coli, resulting loss barrier function membrane. The inner then disintegrated hydrophobic hydrocarbon chains domains membrane, leading cytoplast leakage. formation these enables more efficient bacterial which endows high activity.

Language: Английский

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