A novel antimicrobial polymer efficiently treats multidrug-resistant MRSA-induced bloodstream infection

Abstract

Abstract The present study aimed to ascertain if polymer 2a, a novel synthesized antimicrobial polyionene, could treat methicillin-resistant Staphylococcus aureus (MRSA)-induced bloodstream infection. The minimum inhibitory concentration (MIC) of polymer 2a against MRSA was detected. A time-kill assay was employed to determine the killing kinetic of polymer 2a. Potential antimicrobial mechanisms of polymer 2a, including membrane disruption and programmed cell death (PCD), were explored. A resistance development assay was introduced to determine the propensity of polymer 2a toward resistance against MRSA. A mouse model of MRSA bacteremia was established to assess in vivo efficacy of polymer 2a. Furthermore, in vivo toxicity of polymer 2a was also evaluated through injection by tail vein. Polymer 2a exhibited more superior antimicrobial activity and faster killing kinetic than the control antibiotics against clinically isolated MRSA strains. Polymer 2a resulted in an obvious leakage of cellular components (concentration more than 1× MIC). mRNA expression of PCD pathway-related gene (recA) was significantly up-regulated in the presence of polymer 2a with low concentration (concentration less than 1× MIC). Repeated use of polymer 2a did not lead to drug resistance. In a MRSA-induced bloodstream infection mouse model, polymer 2a displayed superior therapeutic efficacy with negligible systemic toxicity. Moreover, polymer 2a treatment by tail vein could evidently reduce MRSA counts in blood and major organs and markedly improve living conditions. In conclusion, all these findings presented in this work convincingly suggested that polymer 2a may be a promising therapeutic alternative for treating MRSA-induced infections, especially bloodstream infection.