AadA36, a novel chromosomal aminoglycoside nucleotidyltransferase from a clinical isolate of Providencia stuartii

Abstract

In this study, we characterized a novel chromosome-encoded aminoglycoside nucleotidyltransferase (ANT), AadA36, from the Providencia stuartii strain P14 isolated from the sputum specimen of a burn patient at a hospital in Wenzhou, China. Among the functionally characterized ANTs, AadA36 shared the highest amino acid sequence identity of 51.91% with AadA14. The whole genome of P. stuartii P14 consisted of one chromosome and two plasmids (designated pP14-166 and pP14-114). A total of 19 genes with ≥80% similarity with functionally characterized antimicrobial resistance genes (ARGs) were identified in the whole genome, including aminoglycosides [aac(2′)-Ia, aph(6)-Id, aph(3″)-Ib, aac(6′)-Ib, ant(3″)-IIa, aph(3′)-Ia], β-lactams (blaCMY-2 and blaOXA-10) and so on. Antimicrobial susceptibility testing showed that the aadA36 gene conferred specific resistance to spectinomycin and streptomycin, and the minimum inhibitory concentration (MIC) of these antimicrobials increased 128- and 64-fold compared with the control strain. The kinetic parameters of AadA36 were consistent with the MIC data of spectinomycin and streptomycin, with kcat/Km ratios of (1.07 ± 2.23) × 104 M−1 s−1 and (8.96 ± 1.01) × 103 M−1 s−1, respectively. The identification of a novel aminoglycoside resistance gene will help us further understand the complexity of the resistance mechanisms and provide deep insights into the dissemination of resistance genes in the microbial population.

Bacteriophage LHE83 targeting OmpA as a receptor exhibited synergism with spectinomycin against Escherichia coli

“…Bacteria have developed complex mechanisms to confer strong resistance to antibiotics, such as the modification in cell membrane permeability, production of aminoglycoside-modifying enzymes, alteration in drug targets on ribosomes, and acquisition/activation of multidrug efflux pump ( Gao et al, 2022 ; Zhang et al, 2023 ). Our investigation indicated a synergy mechanism between SPEC and phage.…”