Environment Shapes the Accessible Daptomycin Resistance Mechanisms in Enterococcus faecium

Area of Science:

• Microbiology
• Molecular Biology
• Genetics

Background:

• Daptomycin is a crucial antibiotic targeting bacterial cell membranes.
• Bacteria develop resistance by modifying cell envelopes to evade daptomycin.
• The LiaFSR system is key in Enterococcus faecalis daptomycin resistance.

Purpose of the Study:

• Investigate daptomycin resistance evolution in a multidrug-resistant Enterococcus faecium strain.
• Identify environmental influences on resistance mechanisms.
• Characterize the genetic basis of daptomycin resistance.

Main Methods:

• Studied a clinical strain of multidrug-resistant Enterococcus faecium.
• Analyzed evolutionary trajectories in planktonic and biofilm environments.
• Utilized genetic analysis to identify mutations in resistance pathways (e.g., yvcRS, dltABCD, mprF, divIVA, oatA, cls).

Main Results:

• Planktonic environments selected for increased cell surface charge (via yvcRS, dltABCD, mprF) reducing daptomycin binding.
• Biofilm environments favored diversion and repulsion strategies (via divIVA, oatA).
• Both environments converged on cardiolipin synthase (cls) mutations, indicating membrane modification importance.

Conclusions:

• Enterococcus faecium employs diverse, environmentally-shaped evolutionary routes to daptomycin resistance.
• Multiple resistance strategies can coexist, creating a polymorphic resistant population.
• This adaptability makes Enterococcus faecium a challenging nosocomial pathogen.