Investigation of Genetic Diversity of the bla SHV Gene and Development of an Oligonucleotide Microarray to Detect Mutations in the bla SHV Gene

Abstract

SHV β-lactamases, including SHV extended-spectrum β-lactamases, are widespread throughout the world, and confer a broad spectrum of resistance to antibiotic drugs. Mutations ranging from single base-pair substitutions to small deletions within bla_SHV often result in diminished activity and an increased susceptibility to β-lactamase inhibitors. Here, we collected 1,320 clinical isolates from three hospitals in Shanghai. We developed a novel oligonucleotide microarray to detect mutations in the bla_SHV gene, and validated the array data by direct sequencing. Sixty-two of the 1,320 isolates carried the bla_SHV gene. The genotypes of these 62 isolates were successfully called by the microarray and were consistent with the genotypes identified by bidirectional sequencing. Sixteen different bla_SHV alleles were identified. The SHV-1 variant was the most frequent (32.26%), followed by SHV-11 (27.42%) and SHV-12 (25.81%). Of the 62 isolates, 12 contained two different bla_SHV alleles. Our microarray significantly facilitated the identification of bla_SHV variants, which makes it an attractive option for the detection of SHV variants in clinical laboratories.