Analysis of class I integrons responsible for antibiotics resistance in Pseudomonas aeruginosa

Abstract

An increase in resistance to antibiotics in Pseudomonas aeruginosa has become a major worldwide concern. Particularly, P. aeruginosa which produces carbapenemases, versatile metallo-β-lactamases (MBLs), causes limitation to treat infection. Class I integrons play an important role in the spread of antibiotic resistance determinants such as MBLs in P. aeruginosa. In the present study, we identified and characterized genetic contents of class I integrons in P. aeruginosa DK45 that was isolated from catheterized urine of patients at Chungbuk National University Hospital in South Korea and strongly exhibited carbapenemase activity. The correlation between integron-associated gene cassettes and antibiotics resistance was also investigated. Screening of the integrons in P. aeruginosa was performed by PCR and the integron-associated gene cassettes were further characterized by DNA sequencing. It was confirmed that three integrons (class I) harboring VIM-2, OXA-10, and OXA-30 type β-lactamase genes, respectively, existed on the bacterial plasmid. Each integron also contained genes encoding resistance determinants to various antibiotics such as aminoglycoside, fluoroquinolone and folate pathway inhibitors. Functional analysis by recombinant plasmids bearing each integron in Escherichia coli indicated that each integron was associated to a high resistance rate to β-lactam and aminoglycoside antibiotics. The combined results suggest that genetic diversity of class I integrons is a major factor capable of increasing a broad spectrum resistance to the antibiotics.