Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
The Charles T. Campbell Ophthalmic Microbiology Laboratory, UPMC Eye Center, Ophthalmology and Visual Sciences Research Center, The Eye and Ear Institute, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
PLoS One. 2021 Apr 14;16(4):e0250084. doi: 10.1371/journal.pone.0250084. eCollection 2021.
Enterococcus faecalis are hospital-associated opportunistic pathogens and also causative agents of post-operative endophthalmitis. Patients with enterococcal endophthalmitis often have poor visual outcomes, despite appropriate antibiotic therapy. Here we investigated the genomic and phenotypic characteristics of E. faecalis isolates collected from 13 patients treated at the University of Pittsburgh Medical Center Eye Center over 19 years. Comparative genomic analysis indicated that patients were infected with E. faecalis belonging to diverse multi-locus sequence types (STs) and resembled E. faecalis sampled from clinical, commensal, and environmental sources. We identified known E. faecalis virulence factors and antibiotic resistance genes in each genome, including genes conferring resistance to aminoglycosides, erythromycin, and tetracyclines. We assessed all isolates for their cytolysin production, biofilm formation, and antibiotic susceptibility, and observed phenotypic differences between isolates. Fluoroquinolone and cephalosporin susceptibilities were particularly variable between isolates, as were biofilm formation and cytolysin production. In addition, we found evidence of E. faecalis adaptation during recurrent endophthalmitis by identifying genetic variants that arose in sequential isolates sampled over eight months from the same patient. We identified a mutation in the DNA mismatch repair gene mutS that was associated with an increased rate of spontaneous mutation in the final isolate from the patient. Overall this study documents the genomic and phenotypic variability among E. faecalis causing endophthalmitis, as well as possible adaptive mechanisms underlying bacterial persistence during recurrent ocular infection.
粪肠球菌是医院相关的机会性病原体，也是术后眼内炎的病原体。尽管进行了适当的抗生素治疗，患有肠球菌性眼内炎的患者视力预后仍较差。在这里，我们研究了在过去 19 年中，从匹兹堡大学医学中心眼科中心治疗的 13 名患者中收集的粪肠球菌分离株的基因组和表型特征。比较基因组分析表明，患者感染的粪肠球菌属于不同的多位点序列型（ST），与从临床、共生和环境来源中分离的粪肠球菌相似。我们在每个基因组中都鉴定了已知的粪肠球菌毒力因子和抗生素耐药基因，包括赋予对氨基糖苷类、红霉素和四环素的耐药性的基因。我们评估了所有分离株的细胞毒素产生、生物膜形成和抗生素敏感性，并观察到分离株之间的表型差异。氟喹诺酮类和头孢菌素类的敏感性在分离株之间差异特别大，生物膜形成和细胞毒素产生也是如此。此外，我们通过鉴定在来自同一患者的 8 个月内连续分离的序列中出现的遗传变异，发现了粪肠球菌在复发性眼内炎中适应的证据。我们在 DNA 错配修复基因 mutS 中发现了一个突变，该突变与患者最后一个分离株的自发突变率增加有关。总的来说，这项研究记录了引起眼内炎的粪肠球菌的基因组和表型变异性，以及在复发性眼部感染期间细菌持续存在的可能适应机制。
