A novel antibiotic combination of linezolid and polymyxin B octapeptide PBOP against clinical Pseudomonas aeruginosa strains.

BACKGROUND: Antibiotic-resistant Gram-negative bacteria are becoming a major public health threat such as the important opportunistic pathogen Pseudomonas aeruginosa (P. aeruginosa). The present study investigated enhancement of the linezolid spectrum, which is normally used to treat Gram-positive bacteria, at inhibiting P. aeruginosa growth. METHODS: The checkerboard test or time-kill assay were carried out to determine the antibacterial effects of linezolid in cooperation with polymyxin B octapeptide PBOP (LP) against P. aeruginosa based on in vitro model. The protective effect of LP against P. aeruginosa infection was assessed based on a Caenorhabditis elegans (C. elegans) model. RESULTS: The synergistic activity and antibacterial effects were significantly increased against P. aeruginosa by LP treatment, while linezolid and PBOP as monotherapies exhibited no remarkably bactericidal activity against the clinical strains. Additionally, LP treatment modified biofilm production, morphology, swimming motility of P. aeruginosa, and protected C. elegans from P. aeruginosa infection. CONCLUSIONS: This research demonstrates that LP combination has significant synergistic activity against P. aeruginosa, and PBOP is potential to be an activity enhancer. Notably, this strategy improved the antibacterial activity spectrum of linezolid and other anti-Gram-positive agents and represents an effective choice to surmount the antibiotic resistance of bacteria in the long term.

Phenotypic and genetic characterization of Pseudomonas aeruginosa isolate COP2 from the lungs of COPD patients in China.

Pseudomonas aeruginosa is an important opportunistic pathogen normally associated with increasing morbidity and mortality of immunocompromised hosts with respiratory infections. The phenotypic and genetic features of P. aeruginosa from patients with chronic obstructive pulmonary disease (COPD) remain poorly understood. By using the sputum samples of 25 hospitalized COPD patients from the affiliated hospital of Southwest Medical University (China), we identified a P. aeruginosa isolate, COP2, which showed multiple antibiotic resistance and enhanced Pseudomonas quinolone signal (PQS) production but decreased motility, biofilm formation and virulence compared with the model strain PAO1. Importantly, COP2 harbored a substantial amount of mutations that might influence the functions of 1771 genes in the genome and the evolutionary status of this isolate was clearly distinct from the PAO1 lineage. Accordingly, COP2 had a discrepant transcriptional pattern relating to flagellar assembly, antibiotic resistance, biofilm and PQS production, and can increase the capacities of compound degradation in response to resource/space stresses. Therefore, the identification of COP2 in this study provides preliminary information regarding the genetic features and survival strategy of P. aeruginosa in colonizing COPD lungs and lays the foundations for further understanding of the pathogenic mechanisms of pseudomonal infections.