Antimicrobial macromolecules: synthesis methods and future applications

Abstract

This review article presents important and recent progress in the manufacture and application of antimicrobial macromolecules. Microbial infections continue to endanger human health and pose a great economic burden to society. To resolve this crisis, huge efforts to improve or develop macromolecules that can inhibit pathogens without incurring pathogen resistance are required and actively ongoing. Synthetic antimicrobial macromolecules which include antimicrobial peptides (AMPs), polymers and peptide-polymer hybrids represent a huge class of molecules which can incur effective antimicrobial therapy due to their unique biochemical properties. The use of these antimicrobial macromolecules which target the cytoplasmic membrane of microbes, is a promising approach to lower the propensity of pathogen resistance development. Therefore, huge efforts to synthesize these molecules at scales and purities that enable their structure-function and clinical studies are actively underway. Due to the high cost involved in extracting AMPs from natural sources, biological processes are being developed to economically manufacture AMPs at large scale. Synthetic AMP analogs are also being engineered to further improve antimicrobial potency and lower synthesis cost. Synthetic polymers have also been found to exhibit excellent antimicrobial properties which are comparable to those of natural AMPs. Various antimicrobial polymers have been synthesized based on the amphiphilicity of natural AMPs. Although the facile synthesis of polymers poses no cost problems, numerous synthetic antimicrobial polymers are disadvantaged by high toxicity to mammalian cells due to their non-selectivity. To combine the advantages of AMPs and antimicrobial polymers, peptide-polymer hybrid macromolecules are actively being developed, with a few effective and strongly microbicidal models recently demonstrated. With the advancement of biochemical engineering tools and chemical synthesis methods, these antimicrobial macromolecules can be specifically designed to be highly selective, broad spectrum and biocompatible. In this review, we summarize the recent advances and challenges in the manufacture of these antimicrobial macromolecules. Based on their antimicrobial mechanisms, their applications in addressing challenges associated with infectious disease and antibiotic-resistance are also discussed.

Azetidinium Functionalized Polytetrahydrofurans: Antimicrobial Properties in Solution and Application to Prepare Non Leaching Antimicrobial Surfaces

“…In the last decade many reports were published on antimicrobial polymers containing cationic groups like quaternary ammonium, pyridinium, etc. [7][8][9][10]. For example, Tiller et al, prepared antimicrobial glass surface by attaching poly(4-vinyl-N-alkylpyridinium bromide) to glass slides via covalent linkage [11].…”

Development of paper-based color test-strip for drug detection in aquatic environment: Application to oxytetracycline

“…There are three main risks deriving from the presence of antibiotics in the waters: direct organic damage to water; impact on the biotic environment; and lastly, the most feared one, indirect effects on health via resistant microorganisms (Kemper, 2008;Li et al, 2012;Luis Martinez, 2009;Sarmah et al, 2006). The increasing emergence of antibiotic resistance in human pathogens is today a great concern to public health, not only for hindering the successful treatment of infectious diseases, but also for obstructing the combat to other 4 pathologies in which antibiotic prophylaxis is needed for avoiding associated infections (Luis Martinez, 2009;World Health Organization, 2000).…”

Membrane-Bound Conformations of Antimicrobial Agents and Their Modes of Action

“…Structure-function studies on such polymers, along with the effect of overall charge and hydrophobic content, have also involved the effect of distribution of hydrophobicity over the molecular structure [98]. Antimicrobial polymers have been designed by distributing the charge and hydrophobicity either along the backbone or side chains [57,98,[121][122][123][124][125][126][127][128][129]. In the case of the former, a further design element could be the arrangement of these cationic and hydrophobic monomers (random, alternating, and block).…”