Characterization of the Genetic Environment of the bla_VEB-4 Gene, Associated with a Transposable Region in a Proteus mirabilis Clinical Isolate

Proteus mirabilis is the second most common cause of urinary tract infections and is also an important cause of nosocomial infections. TEM-type and CTX-M-type extended-spectrum β-lactamases (ESBLs) are the most widely distributed in this bacterial species, but minor ESBLs such as the VEB-type have also been identified. The aim of this study was to analyze the genetic environment of the bla_VEB-4 gene found in a P. mirabilis clinical isolate recovered in Spain. P. mirabilis N2231 showed resistance to penicillins, cephalosporins, and aminoglycosides, remaining susceptible to imipenem, cefoxitin, β-lactamases inhibitors, and quinolones. Southern blot analysis revealed that bla_VEB-4 was located in the chromosome. Analysis of the bla_VEB-4 genetic context revealed a 15 kb segment 98% identical to the multidrug resistance (MDR) region of a Salmonella genomic island 1 (SGI1), which included a class 1 integron belonging to the In104 family, previously described in bla_VEB-6-producing P. mirabilis VB1248. bla_VEB-4 was surrounded by repeat elements, transposon Tn1721, and located on a class 1 integron containing aacA4-aadB-dfrA1-orfC genes. The bla_VEB-4 gene was inserted in a complex structure of a class 1 integron, which is part of an MDR region of an SGI1, possibly involved in the mobilization of the gene and homologous recombination.