Aminoglycoside-modifying enzyme and 16S ribosomal RNA methyltransferase genes among a global collection of Gram-negative isolates

Abstract

The prevalence of genes encoding aminoglycoside-modifying enzymes (AMEs) and 16S rRNA methyltransferases among 200 Gram-negative clinical isolates resistant to different aminoglycosides and collected worldwide during 2013 was evaluated. Selected AMEs and 16S rRNA methyltransferase genes were screened by PCR/sequencing among 49 Acinetobacter spp., 52 Pseudomonas aeruginosa and 99 Enterobacterales. In total 72 isolates carried aac(6')-lb variants (36.0% overall; 55.6% Enterobacterales): 30 aac(6')-Ib-cr, 21 aac(6')-Ib and 21 aac(6')-Ib-like displaying substitutions L119S (alone or in combination with V71A or R173K) or S100G. Ten aph(3')-VI variants were detected among 35 isolates (46.9% of Acinetobacter spp.). Nineteen isolates carried variants of aac(3)-I, with aac(3)-Ia (n=13, mostly Acinetobacter spp.) being the most prevalent. Other AME genes detected were ant(3″)-Ia (n=41), ant(2″)-Ia (n=24), aac(3)-IIe (n=23), aac(3)-IId (n=21), aac(6')-Im (n=13, mostly P. aeruginosa), aacA8 (n=3), aac(3)-IIf (n=1) and aac(3)-IVa (n=1). Among 42 isolates resistant to amikacin, gentamicin and tobramycin tested for 16S rRNA methyltransferase genes, 21 (50.0%) tested positive; armA was most common (n=14), but 4 isolates carried rmtB1, 2 rmtF1 and 1 new variant rmtB4. Over 60 gene combinations, consisting of one to four AMEs and 16S rRNA methyltransferases, were observed. Cloning genes not previously characterised revealed diverse aminoglycoside resistance patterns for some AMEs, but expected results for rmtB4. Studies broadly evaluating these aminoglycoside resistance genes are needed. Using agents stable in the presence of these resistance genes might help overcome resistance.