[Evolution and the flanking sequences of Β-lactamase resistance gene bla_OKP]

bla_OKP genes are chromosomally encoded beta-lactamases that mediate several classes of antibiotics resistance. To investigate the evolution and flanking sequences of OKP beta-lactamase gene, the gene bla_OKP and its flanking sequences from a newly isolated Klebsiella pneumoniae were studied using whole genome sequencing. The flanking sequences of different variant bla_OKP genes and bla_SHV, another plasmid-encoded beta-lactamase gene, were then compared. These studies show that the bla_OKP and bla_SHV genes evolve differently and belong to two different evolution branches. The bla_OKP gene variants can be divided into subgroups: bla_OKP-A and bla_OKP-B. Although both bla_OKP and bla_SHV genes have no mobile genetic elements in their flanking sequences, their genetic environments are quite different. The bla_OKP gene is adjacent to KdpC while bla_SHV gene is flanked by RecF and ygbN-ygbM-ygbK. Furthermore, there are a variety of mobile genetic elements in the neighboring sequence plasmid-encoded bla_SHV genes that are absent in bla_OKP genes. These structural differences may slow the evolution of bla_OKP gene. Collectively, we demonstrate that the evolution and flanking sequence of bla_OKP gene are different from those of the bla_SHV gene, which could be an important reason for its relatively slow evolution.