Abstract

Nosocomial infections caused by Pseudomonas aeruginosa are difficult to treat due to the low permeability of its outer membrane as well as to its remarkable ability to acquire further resistance to antibiotics. Chensinin-1b exhibited antibacterial activity against the tested multiple-drug-resistant bacteria with a MIC ranging between 1.56 and 50μM, except E. cloacae strain 0320 (MREC0320), P. fluorescens strain 0322 (MRPF0322) and E. aerogenes strain 0320 (MREA0320). However, the MIC (25μM) of chensinin-1b to multiple-drug-resistant P. aeruginosa strain (MRPA 0108) was 16-fold higher than that observed to P. aeruginosa susceptible strain CGMCC 1.860 (PA1860). Chensinin-1b was able to disturb the integration of the cytoplasmic membrane of PA1860 and MRPA0108 cells similarly, but the outer membrane permeability of MRPA0108 cells was significantly lower. This low permeability was associated with increased expression of lipopolysaccharide (LPS) in the outer membrane and a decrease in negatively charged phospholipids in the outer membrane leaflet. In addition, the biofilm of MRPA0108 was responsible for the reduced susceptibility to chensinin-1b. A higher concentration of chensinin-1b (12.5µM) was required to maximally inhibit the formation of MRPA0108 biofilm. Notably, chensinin-1b inhibited the formation of MRPA0108 biofilm at concentrations below its MIC value by down-regulating the level of PelA, algD, and PslA gene transcription. Importantly, chensinin-1b had a significant antibacterial effect against MRPA0108 in vivo. Administration of chensinin-1b to mice infected with MRPA 0108 significantly increased survival by 50–70%. Moreover, chensinin-1b reduced the production of pro-inflammatory mediators and correspondingly reduced lung and liver tissue damage in the mouse model of septic shock induced by MRPA 0108. Collectively, these results suggest that chensinin-1b could be an effective antibiotic against multiple-drug-resistant bacterial strains.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.