Optimal Balance of Hydrophobic Content and Degree of Polymerization Results in a Potent Membrane-Targeting Antibacterial Polymer.

Globally, excessive use of antibiotics has drastically raised the resistance frequency of disease-causing microorganisms among humans, leading to a scarcity of efficient and biocompatible drugs. Antimicrobial polymers have emerged as a promising candidate to combat drug-resistance pathogens. Along with the amphiphilic balance, structural conformation and molecular weight (M n) play an indispensable role in the antimicrobial potency and cytotoxic activity of polymers. Here, we synthesize cationic and amphiphilic methacrylamide random copolymers using free-radical copolymerization. The mole fraction of the hydrophobic groups is kept constant at approximately 20%, while the molecular weight (average number of linked polymeric units) is varied and the antibacterial and cytotoxic activities are studied. The chemical composition of the copolymers is characterized by 1H NMR spectroscopy. We observe that the average number of linked units in a polymer chain (i.e., molecular weight) significantly affects the polymer activity and selectivity. The antibacterial efficacy against both of the examined bacteria, Escherichia coli and Staphylococcus aureus, increases with increasing molecular weight. The bactericidal activity of polymers is confirmed by live/dead cell viability assay. Polymers with high molecular weight display high antibacterial activity, yet are highly cytotoxic even at 1 × MIC. However, low-molecular-weight polymers are biocompatible while retaining antibacterial potency. Furthermore, no resistance acquisition is observed against the polymers in E. coli and S. aureus. A comprehensive analysis using confocal and scanning electron microscopy (SEM) techniques shows that the polymers target bacterial membranes, resulting in membrane permeabilization that leads to cell death.

Methacrylamide based antibiotic polymers with no detectable bacterial resistance.

The growing number of multidrug-resistant pathogens is a major healthcare concern. In search of alternatives to antibiotics, synthetic mimics of antimicrobial peptides (SMAMPs) in the form of antimicrobial polymers have gained tremendous attention. Here, we report the synthesis of a set of 7 amphiphilic water-soluble cationic copolymers using aminopropyl methacrylamide and benzyl methacrylamide repeat units that show significant antibacterial activity. The antibacterial activity was evaluated using a broth microdilution assay against S. aureus and E. coli, while toxicity to mammalian cells was quantified by hemolysis assay with human red blood cells (RBCs). We find that the antibacterial activity and selectivity of the polymers depends on the mole fraction of aromatic benzyl units (fbenzyl) and the average molecular weight (Mn). Polymers with fbenzyl of 0.10 and 0.19, named AB-10 and AB-19 respectively, exhibited the highest antibacterial efficacy without inducing hemolysis and were chosen for further study. Liposome dye leakage study and observations from confocal and scanning electron microscopy indicate that the AB polymers killed bacterial cells primarily by disrupting the cytoplasmic membrane. No resistant mutants of E. coli and S. aureus were obtained with AB-19 in a 30 day serial passage study.

Amplification of mecA gene in multi-drug resistant Staphylococcus aureus strains from hospital personnel.

BACKGROUND: Antibiotic resistance is common among bacterial pathogens associated with both community acquired and nosocomial infections. In view of the present problem of drug resistance we investigated the prevalence of methicillin resistant Staphylococcus aureus (MRSA) and amplified the mecA gene in the isolates from the hand swabs of the hospital personnel. METHODOLOGY: The nuc gene was amplified to characterize these isolates at species level. The S. aureus isolates were analyzed for their susceptibility to different classes of antibiotics using the disk diffusion method. The spot inoculation test was performed to detect methicillinase production in these isolates. RESULTS: In the screened isolates of S. aureus, 14.2 and 15 kb of plasmids were present. These isolates showed pronounced resistance against beta-lactam antibiotics including second- and third-generation cephalosporins, aminoglycosides, macrolides and fluoroquinolone. Some of the isolates included in this study were resistant to three or more antibiotics. Expression of methicillinase was detected by spot inoculation test, and a few of the isolates were found to produce methicillinase. Moreover, mecA gene was also amplified. Of 17 isolates only 7 showed presence of mecA gene. CONCLUSION: This study highlights the emerging trend of multiple drug resistance in S. aureus strains isolated from hospital personnel working in a premier hospital in North India.