Intestinal Bile Acids Induce a Morphotype Switch in Vancomycin-Resistant Enterococcus that Facilitates Intestinal...

Area of Science:

• Microbiology
• Bacteriology
• Pathogen Biology

Background:

• Vancomycin-resistant Enterococcus (VRE) are significant nosocomial pathogens causing severe infections.
• VRE exhibit high antibiotic resistance and transmissibility, posing a major healthcare challenge.
• Secondary bile acids, like lithocholic acid (LCA), are abundant in the human gut microbiome.

Purpose of the Study:

• To investigate the effect of lithocholic acid (LCA) on VRE morphology and virulence.
• To identify VRE genetic mechanisms involved in response to LCA.
• To explore potential non-bactericidal therapeutic strategies against VRE colonization.

Main Methods:

• Treatment of VRE with lithocholic acid (LCA) in vitro.
• Assessment of VRE cell division, chain formation, and biofilm development.
• Experimental evolution of VRE under LCA pressure and subsequent genetic analysis.
• Evaluation of VRE colonization in a murine model.

Main Results:

• LCA induced VRE to form long chains and enhanced biofilm formation by impairing cell separation.
• Divalent cations effectively reversed the LCA-induced VRE chaining and biofilm formation.
• Experimental evolution identified mutations in yycG/walK and liaR that locked VRE in a diplococcal state, reduced biofilm, and increased daptomycin susceptibility.
• Mutant VRE strains exhibited impaired intestinal colonization due to compromised competition with gut microbiota.

Conclusions:

• Lithocholic acid (LCA) significantly alters VRE morphology and virulence properties.
• Targeting the LCA-induced morphotype switch represents a novel non-bactericidal approach to combat VRE.
• This strategy may be particularly useful for VRE decolonization in immunocompromised patients, such as those undergoing stem cell transplantation.