为研究β-内酰胺酶耐药基因bla_OKP进化及其侧翼序列情况,本文通过全基因组测序技术对肺炎克雷伯氏菌进行测定,分析了其中bla_OKP基因及其侧翼序列的特征,同时与不同亚型的bla_SHV侧翼序列进行了对比。研究发现,bla_OKP、bla_SHV基因进化差异明显,分为两个进化支,其中bla_OKP分为两个进化亚组(bla_OKP-A和bla_OKP-B)。侧翼序列分析结果表明,bla_OKP基因的侧翼序列中无可移动遗传元件,与染色体介导的基因bla_SHV的侧翼序列结构相似,但存在差异,主要表现为bla_OKP基因的一侧与KdpC相连,bla_SHV基因的一侧与RecF相连并具有ygbN-ygbM-ygbK结构。同时由质粒介导的bla_SHV基因的两侧存在多种可移动遗传元件。这些结构差异可能是导致bla_OKP耐药基因进化缓慢的原因之一。本研究通过对bla_OKP基因及其侧翼序列特征进行研究, 研究发现bla_OKP基因及其侧翼序列结构保守是其相对bla_SHV基因进化速度缓慢的重要原因。

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.