Lakhasly

Plazomicin susceptibility testing was performed utilizing strains derived from our recently developed antibiotic resistance platform (ARP)16.

Plazomicin susceptibility testing was performed utilizing strains derived from our recently developed antibiotic resistance platform (ARP)16. This platform is a cell-based array of individual resistance genes present in wild-type E. coli BW25113 and a hyper-permeable, efflux deficient mutant (E. coli BW25113 ΔbamB ΔtolC) of this strain that has increased sensitivity to many antibiotics16. In this survey, gene expression levels were under control of the constitutive Pbla promoter, which results in high-level constitutive resistance to reference aminoglycosides (Table 1). To assess potency, plazomicin was tested against control strains containing only an empty vector (i.e. the wild-type E. coli BW25113 and the hyper-permeable, efflux deficient mutant), which revealed that plazomicin has a comparable potency to the reference aminoglycosides (gentamicin and kanamycin). Furthermore, plazomicin potency was comparable between wild-type E. coli BW25113 and E. coli BW25113 ΔbamB ΔtolC, suggesting that plazomicin is not significantly hindered by the outer membrane and is not a substrate for efflux in E. coli. Overall, plazomicin was profiled against twenty-one aminoglycoside resistance elements, comprising eight AACs, two ANTs, seven APHs and four 16S RMTases. The majority of AMEs did not impact plazomicin potency, with the exception of AAC(2’)-Ia (16-fold increase in MIC) and APH(2’’)-IVa (4- to 8-fold increase in MIC)