No abstract

Painting a glass slide with branched or linear N,N-dodecyl methylpolyethylenimines (PEIs) and certain other hydrophobic PEI derivatives enables it to kill influenza virus with essentially a 100% efficiency (at least a 4-log reduction in the viral titer) within minutes, as well as the airborne human pathogenic bacteria Escherichia coli and Staphylococcus aureus. For most of the coating polyions, this virucidal action is shown to be on contact, i.e., solely by the polymeric chains anchored to the slide surface; for others, a contribution of the polyion leaching from the painted surface cannot be ruled out. A relationship between the structure of the derivatized PEI and the resultant virucidal activity of the painted surface has been elucidated.bactericidal ͉ hydrophobic polyions ͉ virucidal coatings ͉ polyethylenimine ͉ flu I nfluenza virus causes one of the most prevalent human infections: in a typical year, Ϸ15% of the U.S. population is infected, resulting in up to 40,000 deaths and 200,000 hospitalizations (www.cdc.gov͞flu). Furthermore, an influenza pandemic (when a new strain of the virus, to which humans have no immunity, acquires the ability to readily infect people), assuming the estimated mortality rate of the 1918 Spanish flu pandemic (1), might kill some 75 million people worldwide.Influenza (as many other diseases) typically spreads when aerosol particles containing the virus, exhaled or otherwise emitted by an infected person, settle onto surfaces subsequently touched by others (2). Hence, this spread of infection, in principle, could be prevented if common things encountered by people are coated with ''paints'' that inactivate influenza virus.Recently, building on our prior studies with covalently derivatized surfaces (3), we discovered that certain water-insoluble, hydrophobic polycations, e.g., N,N-dodecyl methyl-polyethylenimine (PEI), when painted onto surfaces, kill bacteria on contact because of rupturing of bacterial cell membranes by erect fragments of the polycationic chains (''tentacles'') (4). Because influenza virus, belonging to a class of enveloped viruses, is protected from the outside by a lipid membrane (5, 6), we reasoned that the aforementioned hydrophobic polycations might damage it as well, thereby inactivating the virus. Indeed, in the present study we find that such painted (coated) surfaces, in addition to being extremely bactericidal, also lower the titer of the encountered influenza A virus [the most infectious type in humans (7)] at least 10,000-fold; a relationship between this virucidal activity and the coating polymer structure has been elucidated and rationalized. Results and DiscussionTo mimic a scenario whereby aerosolized aqueous droplets containing influenza virus settle onto surfaces and the virus then spreads (2), we adopted the following approach. A 10-l droplet of a PBS-buffered solution containing (1.6 Ϯ 0.3) ϫ 10 3 pfu of the A͞WSN͞33 (H1N1) strain of influenza virus was placed in the center of a 2.5 ϫ 2.5 cm glass slide (either coated or plain control). Then...

The emergence of multidrug resistant bacteria compounded by the depleting arsenal of antibiotics has accelerated efforts toward development of antibiotics with novel mechanisms of action. In this report, we present a series of small molecular antibacterial peptoid mimics which exhibit high in vitro potency against a variety of Gram-positive and Gram-negative bacteria, including drug-resistant species such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. The highlight of these compounds is their superior activity against the major nosocomial pathogen Pseudomonas aeruginosa. Nontoxic toward mammalian cells, these rapidly bactericidal compounds primarily act by permeabilization and depolarization of bacterial membrane. Synthetically simple and selectively antibacterial, these compounds can be developed into a newer class of therapeutic agents against multidrug resistant bacterial species.

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

The alarming growth of antibiotic resistant superbugs such as vancomycin-resistant Enterococci and Staphylococci has become a major global health hazard. To address this issue, we report the development of lipophilic cationic vancomycin analogues possessing excellent antibacterial activity against several drug-resistant strains. Compared to vancomycin, efficacy greater than 1000-fold was demonstrated against vancomycin-resistant Enterococci (VRE). Significantly, unlike vancomycin, these compounds were shown to be bactericidal at low concentrations and did not induce bacterial resistance. An optimized compound in the series, compared to vancomycin, showed higher activity in methicillin-resistant Staphylococcus aureus (MRSA) infected mouse model and exhibited superior antibacterial activity in whole blood with no observed toxicity. The remarkable activity of these compounds is attributed to the incorporation of a new membrane disruption mechanism into vancomycin and opens up a great opportunity for the development of novel antibiotics.