Role of Aminoglycoside-Modifying Enzymes (AMEs) in Resistance to Aminoglycosides among Clinical Isolates of Pseudomonas aeruginosa in the North of Iran

Abstract

In recent years, the prevalence of resistance to aminoglycosides among clinical isolates of Pseudomonas aeruginosa is increasing. The aim of this study was to investigate the role of aminoglycoside-modifying enzymes (AMEs) in resistance to aminoglycosides in clinical isolates of P. aeruginosa. The clinical isolates were collected from different hospitals. Disk agar diffusion test was used to determine the antimicrobial resistance pattern of the clinical isolates, and the minimum inhibitory concentration of aminoglycosides was detected by microbroth dilution method. The PCR was performed for discovery of aminoglycoside-modifying enzyme-encoding genes. Among 100 screened isolates, 43 (43%) isolates were resistant to at least one tested aminoglycosides. However, 13 (13%) isolates were resistant to all tested aminoglycosides and 37 isolates were detected as multidrug resistant (MDR). The resistance rates of P. aeruginosa isolates against tested antibiotics were as follows: ciprofloxacin (41%), piperacillin-tazobactam (12%), cefepime (32%), piperacillin (26%), and imipenem (31%). However, according to the MIC method, 13%, 32%, 33%, and 37% of the isolates were resistant to amikacin, gentamicin, tobramycin, and netilmicin, respectively. The PCR results showed that AAC(6 ′ )-Ib was the most commonly (26/43, 60.4%) identified AME-encoding gene followed by AAC(6 ′ )-IIa (41.86%), APH(3 ′ )-IIb (34.8%), ANT(3 ″ )-Ia (18.6), ANT(2 ″ )-Ia (13.95%), and APH(3 ″ )-Ib (2.32%). However, APH(3 ′ )-Ib was not found in any of the studied isolates. The high prevalence of AME-encoding genes among aminoglycoside-resistant P. aeruginosa isolates in this area indicated the important role of AMEs in resistance to these antibiotics similar to most studies worldwide. Due to the transmission possibility of these genes between the Gram-negative bacteria, we need to control the prescription of aminoglycosides in hospitals.

Aminoglycoside-Modifying Enzymes Are Sufficient to Make Pseudomonas aeruginosa Clinically Resistant to Key Antibiotics

“…Horizontal gene transfer promotes the dissemination of aminoglycoside and other resistance genes among clinical isolates of P. aeruginosa, an increasing cause of concern in recent years [26][27][28][29]. Acquired resistance genes encode aminoglycoside-modifying enzymes (AMEs) that inactivate AGs by catalysing modifications at OH or NH 2 groups of Antibiotics 2022, 11, 884 2 of 16 the 2-deoxystreptamine sugar moieties by phosphorylation (aminoglycoside phosphoryltransferases [Aph]), acetylation (aminoglycoside acetyltransferases [Aac]) or adenylation (aminoglycoside nucleotidyltransferases/ adenylyltransferase [Ant]) [7,29].…”

“…Isolates of P. aeruginosa that are resistant to aminoglycosides often contain AMEs [ 28 , 29 , 32 ]. However, to the best of our knowledge, the extent to which AMEs increase tolerance to aminoglycosides in clinical isolates and how their effects are influenced by the MexXY-OprM efflux pump has not been quantified.…”