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1. Modification of narrow‐spectrum peptidomimetic polyurethanes with fatty acid chains confers broad‐spectrum antibacterial activity

   https://doi.org/10.1002/pi.5773  

   Peng, Chao ; Zhang, Tian ; Ortiz‐Ortiz, Deliris N. ; Vishwakarma, Apoorva ; Barton, Hazel A. ; Joy, Abraham ( February 2019 , Polymer International)

   Each year, thousands of patients die from antimicrobial‐resistant bacterial infections that fail to respond to conventional antibiotic treatment. Antimicrobial polymers are a promising new method of combating antibiotic‐resistant bacterial infections. We have previously reported the synthesis of a series of narrow‐spectrum peptidomimetic antimicrobial polyurethanes that are effective against Gram‐negative bacteria, such asEscherichia coli; however, these polymers are not effective against Gram‐positive bacteria, such asStaphylococcus aureus. With the aim of understanding the correlation between chemical structure and antibacterial activity, we have subsequently developed three structural variants of these antimicrobial polyurethanes using post‐polymerization modification with decanoic acid and oleic acid. Our results show that such modifications converted the narrow‐spectrum antibacterial activity of these polymers into broad‐spectrum activity against Gram‐positive species such asS. aureus, however, also increasing their toxicity to mammalian cells. Mechanistic studies of bacterial membrane disruption illustrate the differences in antibacterial action between the various polymers. The results demonstrate the challenge of balancing antimicrobial activity and mammalian cell compatibility in the design of antimicrobial polymer compositions. © 2019 Society of Chemical Industry

    

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2. Towards designing globular antimicrobial peptide mimics: role of polar functional groups in biomimetic ternary antimicrobial polymers

   https://doi.org/10.1039/D0SM01896A  

   Rani, Garima ; Kuroda, Kenichi ; Vemparala, Satyavani ( March 2021 , Soft Matter)

   null (Ed.)

   Using atomistic molecular dynamics simulations, we study the interaction of ternary methacrylate polymers, composed of charged cationic, hydrophobic and neutral polar groups, with model bacterial membrane. Our simulation data shows that the random ternary polymers can penetrate deep into the membrane interior and partitioning of even a single polymer has a pronounced effect on the membrane structure. Lipid reorganization, on polymer binding, shows a strong affinity of the ternary polymer for anionic POPG lipids and the same is compared with the control case of binary polymers (only cationic and hydrophobic groups). While binary polymers exhibit strong propensity of acquired amphiphilic conformations upon membrane insertion, our results strongly suggest that such amphiphilic conformations are absent in the case of random ternary polymers. The ternary polymers adopt a more folded conformation, staying aligned in the direction of the membrane normal and subsequently penetrating deeper into the membrane interior suggesting a novel membrane partitioning mechanism without amphiphilic conformations. Finally, we also examine the interactions of ternary polymer aggregates with model bacterial membranes, which show that replacing some of the hydrophobic groups by polar groups leads to weakly held ternary aggregates enabling them to undergo rapid partitioning and insertion into membrane interior. Our work thus underscores the role of inclusion of polar groups into the framework of traditional binary biomimetic antimicrobial polymers and suggests different mode of partitioning into bacterial membranes, mimicking antimicrobial mechanism of globular antimicrobial peptides like Defensin. 

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3. Hydrophilic nanoparticles that kill bacteria while sparing mammalian cells reveal the antibiotic role of nanostructures

   https://doi.org/10.1038/s41467-021-27193-9  

   Jiang, Yunjiang ; Zheng, Wan ; Tran, Keith ; Kamilar, Elizabeth ; Bariwal, Jitender ; Ma, Hairong ; Liang, Hongjun ( December 2022 , Nature Communications)

   Abstract To dissect the antibiotic role of nanostructures from chemical moieties belligerent to both bacterial and mammalian cells, here we show the antimicrobial activity and cytotoxicity of nanoparticle-pinched polymer brushes (NPPBs) consisting of chemically inert silica nanospheres of systematically varied diameters covalently grafted with hydrophilic polymer brushes that are non-toxic and non-bactericidal. Assembly of the hydrophilic polymers into nanostructured NPPBs doesn’t alter their amicability with mammalian cells, but it incurs a transformation of their antimicrobial potential against bacteria, including clinical multidrug-resistant strains, that depends critically on the nanoparticle sizes. The acquired antimicrobial potency intensifies with small nanoparticles but subsides quickly with large ones. We identify a threshold size (d silica ~ 50 nm) only beneath which NPPBs remodel bacteria-mimicking membrane into 2D columnar phase, the epitome of membrane pore formation. This study illuminates nanoengineering as a viable approach to develop nanoantibiotics that kill bacteria upon contact yet remain nontoxic when engulfed by mammalian cells. 

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4. Biomimetic antimicrobial polymers—Design, characterization, antimicrobial, and novel applications

   https://doi.org/10.1002/wnan.1866  

   Takahashi, Haruko ; Sovadinova, Iva ; Yasuhara, Kazuma ; Vemparala, Satyavani ; Caputo, Gregory A. ; Kuroda, Kenichi ( October 2022 , WIREs Nanomedicine and Nanobiotechnology)

   Biomimetic antimicrobial polymers have been an area of great interest as the need for novel antimicrobial compounds grows due to the development of resistance. These polymers were designed and developed to mimic naturally occurring antimicrobial peptides in both physicochemical composition and mechanism of action. These antimicrobial peptide mimetic polymers have been extensively investigated using chemical, biophysical, microbiological, and computational approaches to gain a deeper understanding of the molecular interactions that drive function. These studies have helped inform SARs, mechanism of action, and general physicochemical factors that influence the activity and properties of antimicrobial polymers. However, there are still lingering questions in this field regarding 3D structural patterning, bioavailability, and applicability to alternative targets. In this review, we present a perspective on the development and characterization of several antimicrobial polymers and discuss novel applications of these molecules emerging in the field.

   This article is categorized under:

   Therapeutic Approaches and Drug Discovery > Emerging Technologies

   Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease

    

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5. Synthesis of Lysine Mimicking Membrane Active Antimicrobial Polymers

   Ankita Arora ; Wan Zheng ; Hongjun Liang ; Abhijit Mishra ( November 2018 , Advances in Polymer Sciences and Technology)

   Bhuvanesh Gupta ; Anup K.Ghosh ; Atsushi Suzuki ; Sunita Rattan (Ed.)

   Antibiotic resistance in bacteria is a major health concern. Antimicrobial Peptides (AMPs) are efficient in killing most microbes and yet the development of resistance to AMPs is rare. Although AMPs show promising antimicrobial activities, commercializing them as antibiotics is difficult as in vitro extraction and purification of AMPs is complicated and expensive. AMP mimicking antimicrobial polymers can overcome such problems while maintaining the necessary features of AMPs. Here, we have developed meth-acrylamide based polymers to mimic AMPs which possess high antimicrobial activities with low cytotoxicity. Bactericidal and scanning electron microscopy studies show that the synthesized polymers are effective against Gram-positive and Gram-negative bacteria. We find that these polymers are lethal to bacteria and at the same time, they are also non-cytotoxic to mammalian cells, thereby increasing the potential of these polymers to be used as antibiotics. 

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