Abstract
Purpose :
The purpose of this study was to investigate the clinical features of enterococcal endophthalmitis cases as well as the genomic and phenotypic characteristics of the isolated organisms.
Methods :
A total of 15 enterococcal isolates from 13 patients treated for post-operative endophthalmitis at the UPMC Eye Center were collected by the Charles T. Campbell Microbiology Laboratory. Isolates were phenotyped for bioflim formation, cytolysin expression, and susceptibility to relevant antibiotics and disinfectants. Bacterial genomes were sequenced on the Illumina platform, and were compared to one another and to other publicly available genomes. Multilocus sequence types, acquired antibiotic resistance genes, plasmid replicons, and known virulence factors were identified using online tools.
Results :
Comparative genomic analysis indicated that patients were infected with E. faecalis of diverse sequence types associated with clinical, commensal, and environmental sources. We identified the occurrence of known E. faecalis virulence factors and antibiotic resistance genes, including genes conferring resistance to lincosamides, tetracyclines, aminoglycosides, and erythromycin. Susceptibility to fluroquinolone and cephalosporin antibiotics was variable, as was biofilm formation and cytolysin production. We found evidence of E. faecalis adaptation during recurrent endophthalmitis by identifying genetic variants that arose in sequential isolates sampled over an eight-month time period from the same patient. We confirmed that all three isolates from the patient were closely related, and represented the same strain that caused a persistent infection. We also observed a hypermutator phenotype in the last isolate from the patient, which was due to a mutation in the DNA mismatch repair gene mutS. The hypermutator isolate evolved resistance to ceftazidime during the course of antibiotic therapy, and we confirmed its ability to gain ceftazidime resistance by passaging a susceptible parent isolate in increasing antibiotic concentrations.
Conclusions :
Overall this study documents the clinical, genomic and virulence-associated features that enable E. faecalis to cause post-operative endophthalmitis, as well as the adaptive mechanisms underlying bacterial persistence during recurrent ocular infection.
This is a 2020 ARVO Annual Meeting abstract.