Emergence of transferable daptomycin resistance in Gram-positive bacteria

Area of Science:

• Microbiology
• Genetics
• Antimicrobial Resistance

Background:

• Daptomycin is a crucial last-resort antibiotic for treating infections caused by multidrug-resistant Gram-positive bacteria.
• While chromosomal mutations are known to cause daptomycin resistance, transmissible resistance traits have not been previously identified.

Purpose of the Study:

• To report the discovery of an acquired daptomycin resistance determinant.
• To investigate the genetic basis and potential for transmission of this novel resistance mechanism.

Main Methods:

• Detection and characterization of the daptomycin resistance determinant (drc) in a livestock-associated Mammaliicoccus sciuri isolate.
• Genetic analysis of the drc operon (drcAB) and its regulatory system (drcRS).
• Functional analysis of the drc locus in various bacterial backgrounds, including methicillin-resistant Staphylococcus aureus (MRSA).

Main Results:

• Identification of a novel, acquired daptomycin resistance determinant, named drc, in a Mammaliicoccus sciuri strain.
• The drc determinant comprises a two-gene operon (drcAB) regulated by a two-component system (drcRS), mediating daptomycin inactivation.
• The mobile drc locus is functional in diverse bacterial species, including MRSA, and circulates among environmental and commensal Gram-positive bacteria.

Conclusions:

• The discovery of the mobile drc locus represents the first identified acquired daptomycin resistance trait.
• The drc system's functionality in MRSA and its circulation in environmental bacteria pose a significant risk for transmission to clinical pathogens.
• Low-virulence microorganisms can serve as important reservoirs for antibiotic resistance genes, necessitating enhanced surveillance.