Synthetic Membrane-Targeted Antibiotics

Abstract

Antimicrobial resistance continues to evolve and presents serious challenges in the therapy of both nosocomial and community-acquired infections. The rise of resistant strains like methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Staphylococcus aureus (VRSA) and vancomycin-resistant enterococci (VRE) suggests that antimicrobial resistance is an inevitable evolutionary response to antimicrobial use. This highlights the tremendous need for antibiotics against new bacterial targets. Agents that target the integrity of bacterial membrane are relatively novel in the clinical armamentarium. Daptomycin, a lipopeptide is a classical example of membrane-bound antibiotic. Nature has also utilized this tactic. Antimicrobial peptides (AMPs), which are found in all kingdoms, function primarily by permeabilizing the bacterial membrane. AMPs have several advantages over existing antibiotics including a broad spectrum of activity, rapid bactericidal activity, no cross-resistance with the existing antibiotics and a low probability for developing resistance. Currently, a small number of peptides have been developed for clinical use but therapeutic applications are limited because of poor bioavailability and high manufacturing cost. However, their broad specificity, potent activity and lower probability for resistance have spurred the search for synthetic mimetics of antimicrobial peptides as membrane-active antibiotics. In this review, we will discuss the different classes of synthetic membrane-bound antibiotics published since 2004.

Antibacterial effects and action modes of asiatic acid

“…That is, this compound is applicable for raw and cold foods, as well as food products treated with high temperature, short time pasteurization. Bacterial membrane integrity is important not only for bacteria's self-protection but also for the functions of membrane-associated enzymes responsible for energy generation, respiration, and redox balance [24,25]. Thus, bacterial membrane rupture easily impairs these critical functions, which in turn affects the bacteria's survival and growth.…”

New trends in peptide-based anti-biofilm strategies: a review of recent achievements and bioinformatic approaches

“…Recently, some reviews (Vooturi and Firestine 2010;Giuliani and Rinaldi 2011) have reported the engineering of AMP mimetics or peptidomimetics, ie non-peptide molecules aimed at retaining and improving the basic features of AMPs.…”

“…LPS and (lipoteichoic acid) LTA binding activity (Giuliani and Rinaldi 2011) DL-Amino acid diastereomers . Do not retain a-helical structure of AMPs (Vooturi and Firestine 2010) . .…”

“…Resistant to proteases . Not cytotoxic on mammalian cells (Vooturi and Firestine 2010) therefore, all D-enantiomers are equally active, giving AMPs a broad action spectrum (Podda et al 2006). The mechanisms of action of AMPs are divided into pore and non-pore models (Wimley and Hristova 2011).…”

Antimicrobial Advances in Treating Periodontal Diseases

“…Efforts are being made to develop antimicrobial peptides with bactericidal properties to kill both gram-positive and gram-negative organisms, and this topic is discussed in the chapter by Gorr [pp. [84][85][86][87][88][89][90][91][92][93][94][95][96][97][98]. Such agents have shown activity against clinically important multi-resistant bacteria, such as vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus [98].…”