Poly(styrene-alt-maleic anhydride) Conjugated with Spermine: Synthesis, Antibacterial Activity and Antibiotic Susceptibility

Hypothesis: In the past decades, the increasing resistance to antibiotics among some nosocomial infection pathogens has been one of the largest challenges of human health. One of the ways to reduce antibiotic resistance in bacteria is the combination use of cationic polymers with antibiotics. Poly(styrene-alt-maleic-anhydride) (PSMA) is an alternative biodegradable copolymer which can react with bioactive agents such as alkyl amines through a ring-opening reaction. In this study, for the first time, the antibacterial activity of poly(styrene-alt-maleic-anhydride) (PSMA) conjugated with spermine (Spm-PSMA) and its influence on resistance of Enterococcus faecalis to ceftazidime and ciprofloxacin antibiotics have been investigated.
Spm-PSMA was synthesized by reaction of PSMA with spermine in the presence of triethylamine catalyst under argon atmosphere at room temperature and characterized by FTIR and DSC. The antibacterial activity of Spm-PSMA was evaluated against two nosocomial infective bacteria, Enterococcus faecalis (E. faecalis) and Acinetobacter baumannii (A. baumannii) by two-fold microdilution method. Its ability to reduce the resistance of E. faecalis to the ciprofloxacin (CP) and ceftazidime (CAZ) antibiotics, active oxygen species (ROS) levels and morphological changes in acidic conditions was evaluated.
Findings: The glass transition temperature of Spm-PSMA (197°C) is higher than that of PSMA (164°C) due to intermolecular hydrogen bonding. Spm-PSMA reduces the growth of Gram-positive E. faecalis in a dose-independent manner, whereas it has no significant antibacterial activity against Gram-negative A. baumannii in acidic condition. E. faecalis susceptibility to ceftazidime and ciprofloxacin antibiotics is increased in the presence of Spm-PSMA at pH 5.5. The SEM results show that Spm-PSMA alone and in combination with antibiotics causes the transformation of E. faecalis cells from coccoid to coccobacilli shape. The results of this study show that Spm-PSMA is a biocompatible polymer with antibacterial activity and antibiotic sensitivity against E. faecalis bacteria.