Molecular characterization of class 1 integrons in carbapenem-resistant Enterobacterales isolates

Abstract

Objective: Carbapenem-resistant Enterobacterales (CRE) infections result in higher treatment costs and mortality rates. Integrons play important roles in emergence and spread of antibiotic resistant genes. To get a better understand on the effects of integron on CRE resistance, distribution of common carbapenemase genes and class 1 integron in clinical CRE isolates were investigated.

Method: Carbapenemase genes, including bla_KPC, bla_VIM, bla_IMP, bla_NDM, bla_GES, bla_VEB and bla_OXA-23, were screened in 161 CRE isolates and subtypes of these genes were confirmed through sequence analysis. Class 1 integron was screened and common promoter and gene cassette arrays were determined by sequencing. The resistant rates to clinical commonly used antibiotics between integron positive and integron negative CRE isolates were compared.

Results: Of 161 CRE isolates, the most prevalent carbapenemase gene was bla_KPC-2, which was detected in 139 isolates, including 99 Klebsiella pneumoniae. Class 1 integron was detected in 78 isolates. Twenty different gene cassettes, including two carbapenemase genes bla_VEB-1 and bla_IMP-4, and nine different gene cassette arrays, including bla_VEB-1-aadB-arr-2-cmlA5-bla_OXA-10-aadA1, aadB-catB8-bla_OXA-10-aadA1-dfrA1-aacA4 and bla_IMP-4-qacG-aacA4-catB3, were detected. Five types of common promoters were identified. Relative weak promoter PcH1 was the dominant type. Resistant rates of CRE isolates containing class 1 integrons to ceftazidime, amikacin, trimethoprim/sulfamethoxazole and gentamicin were higher than those without class 1 integrons (P < 0.05).

Conclusion: Class 1 integrons play important roles in the emergence and spread of CRE resistance. To the best of our knowledge, this is the first report of aadB-catB8-bla_OXA-10-aadA1-dfrA1-aacA4 and bla_IMP-4-qacG-aacA4-catB3 in the same Providencia rettgeri isolate and bla_VEB-1-aadB-arr-2-cmlA5-bla_OXA-10-aadA1 in P. rettgeri.

Keywords: Carbapenem-resistant Enterobacterales; Gene cassettes; Integron; Promoters.