Yehia Fatma Al-Zahraa A, Yahya Galal, Elsayed Eslam M, Serrania Javier, Becker Anke, Gomaa Salwa E
Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
Molecular Biology Institute of Barcelona (IBMB), CSIC, Barcelona, Spain.
Microb Biotechnol. 2025 Jan;18(1):e70075. doi: 10.1111/1751-7915.70075.
Enterococcus species, natural inhabitants of the human gut, have become major causes of life-threatening bloodstream infections (BSIs) and the third most frequent cause of hospital-acquired bacteremia. The rise of high-level gentamicin resistance (HLGR) in enterococcal isolates complicates treatment and revives bacteriophage therapy. This study isolated and identified forty E. faecalis clinical isolates, with 30% exhibiting HLGR. The HLGR5 isolate, resistant to fosfomycin, vancomycin, and linezolid, was used to isolate the vB_EfaS_SZ1 phage from effluent water. This phage specifically lysed 42% of HLGR isolates. vB_EfaS_SZ1 demonstrated beneficial traits, including thermal stability, acid-base tolerance, a short latent period, and a large burst size. The phage genome comprises a 40,942 bp linear double-stranded DNA with 65 open reading frames (ORFs). The genome closely resembled Enterococcus phages, classifying it within the Efquatrovirus genus. Phage-antibiotic synergy was assessed using checkerboard assays and time-killing analyses, revealing enhanced bacteriolytic activity of ampicillin and fosfomycin, with significant reductions in minimum inhibitory concentration values. In a mouse bacteremia model, phage-antibiotic combinations significantly reduced E. faecalis liver burden compared to monotherapies. Histopathological analysis confirmed therapeutic synergy, showing reduced inflammation and improved hepatocyte regeneration. These findings underscore the potential of phage vB_EfaS_SZ1 as an adjunct to antibiotic therapy for resistant enterococcal bacteremia.
肠球菌是人类肠道的天然寄居菌，已成为威胁生命的血流感染（BSIs）的主要原因，也是医院获得性菌血症的第三大常见原因。肠球菌分离株中高水平庆大霉素耐药性（HLGR）的增加使治疗变得复杂，并使噬菌体疗法得以复兴。本研究分离并鉴定了40株粪肠球菌临床分离株，其中30%表现出HLGR。HLGR5分离株对磷霉素、万古霉素和利奈唑胺耐药，用于从废水中分离vB_EfaS_SZ1噬菌体。该噬菌体特异性裂解了42%的HLGR分离株。vB_EfaS_SZ1表现出有益的特性，包括热稳定性、酸碱耐受性、潜伏期短和裂解量大。噬菌体基因组由一个40,942 bp的线性双链DNA组成，有65个开放阅读框（ORF）。该基因组与肠球菌噬菌体非常相似，将其归类于Efquatrovirus属。使用棋盘法和时间杀菌分析评估噬菌体-抗生素协同作用，结果显示氨苄西林和磷霉素的溶菌活性增强，最低抑菌浓度值显著降低。在小鼠菌血症模型中，与单一疗法相比，噬菌体-抗生素联合用药显著降低了粪肠球菌的肝脏负荷。组织病理学分析证实了治疗协同作用，显示炎症减轻，肝细胞再生改善。这些发现强调了噬菌体vB_EfaS_SZ1作为耐药肠球菌菌血症抗生素治疗辅助手段的潜力。
