耐多药沙门氏菌特异性噬菌体的分离、研究及其治疗潜力评价

Khatuna Makalatia, E. Kakabadze, N. Grdzelishvili, N. Bakuradze, N. Chanishvili
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引用次数: 0

摘要

在研究范围内,在亚美尼亚和格鲁吉亚分离出临床非伤寒沙门氏菌,并根据常规微生物学方法和MALDI-TOF ms进行鉴定。对这些分离株进行了进一步的血清分型分析(White-Kauffmann-Le Minor方案),并确定了它们的抗菌药物敏感性谱。共鉴定出40种抗生素耐药谱,其中35种为临床菌株的特征。从345株分离株中,最终选择来自格鲁吉亚、亚美尼亚和爱尔兰的238株用于我们的研究。利用这些菌株,分离出13个具有生物学和遗传特征的新噬菌体。根据获得的数据,对噬菌体进行了分类,并确定了其生命周期的特点(毒溶性,中度溶原性)。测序结果分析显示,12个噬菌体中仅有1个鉴定为温带噬菌体(vB_GEC_ TR),属于足病毒科-拉德伯格病毒属。虽然其他11种噬菌体是有毒的,但它们与已知的和具有特征的噬菌体有关,这些噬菌体用于各种噬菌体制剂。基因组分析未发现溶原性相关基因。其中,6个为肌病毒科成员(vB_GEC_B1、vB_GEC_B3、vB_GEC_MG、vB_GEC_BS、vB_GEC_NS7、vB_GEC_7A), 5个为淋巴病毒科成员(vB_GEC_N5、vB_GEC_N8、vB_GEC_M4、vB_GEC_M5、vB_GEC_Hi)。体外实验表明,噬菌体vB_GEC_B1、vB_GEC_BS、vB_GEC_B3、vB_GEC_NS7、vb - gec_n8对所检菌株具有较高的活性(60% ~ 80%)。噬菌体对临床菌株(≈90%)比对兽医菌株(≈70%)更有效。对这些噬菌体敏感的菌株主要是鼠伤寒沙门氏菌和肠炎沙门氏菌血清型,主要来自临床。根据我们的研究,我们可以得出结论,噬菌体作为治疗耐多药沙门氏菌感染的额外工具的应用似乎是合理的。噬菌体是天然的、特异的抗菌剂,可以溶解细菌。不管它们的抗菌素耐药性状况如何,同时不伤害共生菌群。这是噬菌体与抗生素相比的主要优势之一。本研究中检测的噬菌体在抗耐多药沙门氏菌感染的噬菌体治疗中具有应用潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Isolation and Study of Bacteriophages Specific Against Multidrug Resistant Salmonella spp. and Assessment of their Therapeutic Potential
Within the scope of the study, clinical non-typhoidal Salmonella were isolated in Armenia and Georgia and identified based on conventional microbiological methods and MALDI-TOF MS. These isolates were further analysed by serotyping (White-Kauffmann-Le Minor scheme) and their antimicrobial susceptibility profiles were defined. A total of 40 antibiotic resistance profiles were identified, of which 35 were characteristic of clinical strains. Out of a total of 345 isolates, 238 strains from Georgia, Armenia and Ireland were eventually selected for our study.Using the strains of this collection, 13 new bacteriophages were isolated, characterized by biological and genetic features. Based on the data obtained, phages were classified and the peculiarities of their life cycle were determined (virulent-lytic, moderate-lysogenic).Analysis of the sequencing results showed that only one of the 12 phages identified as temperate phage (vB_GEC_ TR), it belongs to the family Podoviridae, genus-Laderbergvirus. While the other 11 phages are virulent, they are related to well-known and characterized phages, which are used in various phage preparations. Analysis of their genomes did not show any lysogeny associated genes. Among the virulent phages, 6 are members of Myoviridae family (vB_GEC_B1, vB_GEC_B3, vB_GEC_MG, vB_GEC_BS, vB_GEC_NS7, vB_GEC_7A) and 5 of the Syphoviridae family (vB_GEC_N5, vB_GEC_N8, vB_GEC_M4, vB_GEC_M5, vB_GEC_Hi). In vitro tests revealed that the phages - vB_GEC_B1, vB_GEC_BS, vB_GEC_B3, vB_GEC_NS7, vB-GEC-N8 showed high activity (60% to 80%) against the examined strains. The phages have been shown to be more effective against clinical strains (≈90%) than against veterinary strains (≈70%). The strains susceptible to these phages were mainly S.typhimurium and S. Enteritidis serovars and are largely of clinical origin. Based on our research we can conclude that the application of phages as an additional tool for the treatment of MDR Salmonella infections seems to be plausible. Phages are natural and specific antibacterial agents, which can lyse bacteria.irrespective of their AMR status, whilst leaving the commensal microflora unharmed. This is one of the main advantages of phages in comparison to antibiotics. The phages tested in this study showed potential for application in phage therapy against MDR Salmonella infections.
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