vanM, a new glycopeptide resistance gene cluster found in Enterococcus faecium

Area of Science:

• Microbiology
• Molecular Biology
• Genetics

Background:

• Glycopeptide-resistant enterococci (GRE) are a global hospital concern.
• Seven van gene clusters (vanA-G, vanL) are known to confer resistance.
• Enterococcus faecium Efm-HS0661 exhibited high-level resistance to vancomycin and teicoplanin.

Purpose of the Study:

• To investigate the genetic basis of vancomycin and teicoplanin resistance in a clinical Enterococcus faecium strain.
• To identify and characterize a novel van gene cluster responsible for glycopeptide resistance.

Main Methods:

• Conjugation experiments to transfer resistance.
• Polymerase Chain Reaction (PCR) for known van genes.
• Cloning and primer walk sequencing to identify the novel vanM gene cluster.
• Liquid chromatography-mass spectrometry to analyze peptidoglycan precursors.

Main Results:

• A novel van gene cluster, designated vanM, was identified.
• The vanM ligase gene shares amino acid similarities with known Van proteins but has a unique gene cluster organization.
• The vanM cluster is associated with an IS1216-like element, potentially aiding dissemination.
• VanM confers resistance by inducible synthesis of peptidoglycan precursors ending in D-Ala-D-Lac.

Conclusions:

• The discovery of the vanM gene cluster expands the known mechanisms of glycopeptide resistance in enterococci.
• The vanM gene represents a new determinant for high-level vancomycin and teicoplanin resistance.
• The presence of mobile genetic elements suggests potential for future spread of vanM.