Transferable amikacin resistance in gram-negative bacterial isolates

Area of Science:

• Microbiology
• Molecular Biology
• Genetics

Background:

• Enterobacteriaceae are common human pathogens.
• Aminoglycoside antibiotics are crucial for treating bacterial infections.
• Emergence of antibiotic resistance in Enterobacteriaceae is a growing concern.

Purpose of the Study:

• To investigate the mechanisms of amikacin resistance in Enterobacteriaceae.
• To identify novel aminoglycoside resistance genes in clinical isolates.
• To determine the transferability of aminoglycoside resistance.

Main Methods:

• Isolation and characterization of amikacin-resistant Enterobacteriaceae strains.
• In vitro susceptibility testing against various aminoglycosides.
• Phosphocellulose paper binding assays to detect aminoglycoside-modifying enzymes.
• Plasmid analysis and conjugation experiments to assess resistance transfer.

Main Results:

• Seven Enterobacteriaceae strains exhibited resistance to multiple aminoglycosides, including amikacin, gentamicin, and tobramycin.
• Resistance was attributed to the aminoglycoside acetyltransferase AAC(6 extprime)-I enzyme, a mechanism previously identified only in staphylococci and streptococci.
• This AAC(6 extprime)-I mechanism was also found in two Klebsiella pneumoniae isolates.
• Additional enzymes, AAC(3)-II and APH(2 extprime extprime), were detected in some strains.
• Aminoglycoside resistance was transferable via plasmids ranging from 36-45 MD.

Conclusions:

• The study identified a novel aminoglycoside resistance mechanism (AAC(6 extprime)-I) in Enterobacteriaceae, previously unrecognized in this bacterial group.
• The presence of transferable R plasmids encoding these resistance enzymes highlights the potential for rapid dissemination of antibiotic resistance.
• These findings underscore the need for continuous surveillance of antibiotic resistance mechanisms in clinical settings.