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Long-Term Colonization Dynamics of Enterococcus faecalis in Implanted Devices in Research Macaques.

Mia T Lieberman1,2, Daria Van Tyne3,4, JoAnn Dzink-Fox5

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A protocol change reducing antimicrobial use in macaque implants allowed a less resistant Enterococcus faecalis strain (ST48) to dominate. This shift, alongside increased biofilm formation and hypermutator phenotypes, impacts future treatment strategies for these opportunistic pathogens.

Keywords:
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Area of Science:

  • Microbiology and Infectious Diseases
  • Animal Models in Neuroscience Research
  • Antimicrobial Resistance Evolution

Background:

  • Enterococcus faecalis is an opportunistic pathogen frequently colonizing cephalic recording chambers (CRCs) in research macaques.
  • Previous characterization of E. faecalis strains from macaques at MIT in 2011 established baseline data.
  • A 2014 protocol change eliminated antimicrobial use within CRCs, necessitating an evaluation of its impact on E. faecalis colonization.

Purpose of the Study:

  • To investigate the effects of a reduced antimicrobial protocol on colonizing E. faecalis strains in macaque CRCs.
  • To compare E. faecalis strains isolated before and after the 2014 protocol change regarding sequence type, antimicrobial resistance, and biofilm formation.
  • To identify genetic changes, such as mutations in DNA mismatch repair genes, that may confer a survival advantage.

Main Methods:

  • Collected and characterized 20 E. faecalis isolates from 10 macaques between 2013 and 2017.
  • Compared new isolates to 4 previously characterized strains from 2011.
  • Analyzed sequence type (ST) distribution, antimicrobial resistance profiles, biofilm formation capacity, and mutations in mutS and mutL genes.

Main Results:

  • The less antimicrobial-resistant lineage ST48 emerged as dominant after 2013, replacing the previously predominant ST4 and ST55.
  • Two macaques maintained colonization by ST4 and ST55 strains for extended periods (5 and 4 years), showing stable resistance but increased biofilm formation over time.
  • ST48 strains demonstrated robust biofilm formation, and mutations in mutS and mutL genes conferring a hypermutator phenotype were identified in ST55 and ST4 strains.

Conclusions:

  • Reduced antimicrobial pressure favored the proliferation of a less resistant E. faecalis strain (ST48), potentially improving future treatment outcomes.
  • Increased biofilm formation is a key factor in the long-term persistence of E. faecalis in CRCs.
  • The emergence of hypermutator phenotypes in E. faecalis strains poses a challenge for future antimicrobial therapies in macaques.