ena-STUDY-Hopital Henri Mondor APHP-03-03-2019-13:17:43:280-55
Complete genome sequencing of Enterococcus faecalis strains suggests a role of Ebp deletions in infective endocarditis relapses
Background Relapses of infective endocarditis (IE) due to Enterococcus faecalis are not rare, even when appropriate antimicrobial therapy is used. We compared E. faecalis isolates responsible for the first episode and relapse of IE to better understand such therapeutic failures.  Methods One patient with documented E. faecalis IE who completed the recommended treatment and relapsed was studied. Both isolates from the initial episode and the relapse were compared using whole genome sequencing, biofilm formation, growth, and antimicrobial susceptibility assays.  Results We identified large deletions of ~47,000 bp as well as mutations affecting potential regulators in isolates responsible for the relapses. The deletion involved the previously well-described major virulence associated endocarditis and biofilm-associated pili (Ebp operon). EbpA,EbpB, and EbpC, which belong to this operon, also appear to be major targets for the immune system. Five non-synonymous SNPs were also evidenced, one of which was located in the gene encoding RelA, a protein involved in the regulation of the alarmone (p)ppGpp. These features were translated into a decrease in both fitness and biofilm formation, but no increase in antibiotic resistance.  Conclusions Our results suggest that the loss of large chromosomal regions containing genes encoding Ebp proteins, associated with mutations involving potential regulators, may help E. faecalis to evade both antibiotics and the immune system.
Background Relapses of infective endocarditis (IE) due to Enterococcus faecalis are not rare, even when appropriate antimicrobial therapy is used. We compared E. faecalis isolates responsible for the first episode and relapse of IE to better understand such therapeutic failures.  Methods One patient with documented E. faecalis IE who completed the recommended treatment and relapsed was studied. Both isolates from the initial episode and the relapse were compared using whole genome sequencing, biofilm formation, growth, and antimicrobial susceptibility assays.  Results We identified large deletions of ~47,000 bp as well as mutations affecting potential regulators in isolates responsible for the relapses. The deletion involved the previously well-described major virulence associated endocarditis and biofilm-associated pili (Ebp operon). EbpA,EbpB, and EbpC, which belong to this operon, also appear to be major targets for the immune system. Five non-synonymous SNPs were also evidenced, one of which was located in the gene encoding RelA, a protein involved in the regulation of the alarmone (p)ppGpp. These features were translated into a decrease in both fitness and biofilm formation, but no increase in antibiotic resistance.  Conclusions Our results suggest that the loss of large chromosomal regions containing genes encoding Ebp proteins, associated with mutations involving potential regulators, may help E. faecalis to evade both antibiotics and the immune system.