A neglected and emerging antimicrobial resistance gene encodes for a serine-dependent macrolide esterase

Area of Science:

• Microbiology
• Biochemistry
• Genetics

Background:

• The emergence of antimicrobial resistance (AMR) poses a significant global health threat.
• Continuous discovery of novel antimicrobial resistance genes (ARGs) is critical for developing effective countermeasures.
• Macrolide antibiotics are widely used, making resistance mechanisms a key area of study.

Purpose of the Study:

• To identify and characterize novel enzymes responsible for antimicrobial resistance.
• To investigate the function of a newly discovered α/β-hydrolase with potential macrolide-inactivating activity.
• To understand the prevalence and co-occurrence of this enzyme with other ARGs.

Main Methods:

• Bioinformatic analysis to identify potential ARG candidates.
• Enzymatic assays to confirm macrolide inactivation.
• Sequence analysis and characterization of the α/β-hydrolase.
• Environmental and microbiome DNA sequencing to assess gene distribution.

Main Results:

• Identification of a novel serine-dependent α/β-hydrolase with macrolide esterase activity.
• Demonstration of the enzyme's ability to inactivate macrolide antibiotics.
• Evidence of the enzyme's co-occurrence with other emerging ARGs in environmental, animal, and pathogenic samples.

Conclusions:

• The newly identified macrolide esterase represents a significant addition to the known repertoire of antimicrobial resistance mechanisms.
• Its presence in diverse settings highlights the complex and widespread nature of ARG dissemination.
• Further research is warranted to elucidate the full impact of this enzyme on macrolide efficacy and AMR spread.