Tri-Institutional Training Program in Laboratory Animal Medicine and Science, Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, and The Rockefeller University, New York, New York; Center of Comparative Medicine and Pathology, Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine, New York, New York;, Email:
Laboratory of Bacterial Pathogenesis and Immunology, The Rockefeller University, New York, New York.
Comp Med. 2020 Aug 1;70(4):328-335. doi: 10.30802/AALAS-CM-19-000096. Epub 2020 May 29.
is the causative agent of -associated hyperkeratosis in immunocompromised mice. The resulting skin pathology can be profound and can be associated with severe wasting, making the animals unsuitable for research. Although the administration of antibiotics is effective in resolving clinical symptoms, antibiotics do not eradicate the offending bacterium. Furthermore, antibiotic use may be contraindicated as it can affect tumor growth and is associated with enterotoxemia in highly immunocompromised murine strains. Lysins, which are lytic enzymes obtained from bacteriophages, are novel antimicrobial agents for treating bacterial diseases. The advantage of lysins are its target specificity, with minimal off-target complications that could affect the host or the biology of the engrafted tumor. The aim of this study was to identify lysins active against . Chemical activation of latent prophages by using mitomycin C in 3 isolates did not cause bacteriophage induction as determined through plaque assays and transmission electron microscopy. As an alternative approach, 8 lysins associated with other bacterial species, including those from the closely related species were tested for their lytic action against but were unsuccessful. These findings were congruent with the previously reported genomic analysis of 21 isolates, which failed to reveal bacteriophage sequences by using the PHAST and PHASTER web server tools. From these results, we suggest is among those rare bacterial species devoid of lysogenic bacteriophages, thus making the identification of -specific lysins more challenging. However, may be a useful model organism for studying the effects of antiphage systems.
是导致免疫功能低下小鼠相关过度角化的病原体。由此产生的皮肤病理变化可能非常严重,并可能伴有严重消瘦,使动物不适合进行研究。虽然抗生素的给药在解决临床症状方面是有效的,但抗生素并不能根除致病细菌。此外,由于抗生素的使用可能会影响肿瘤的生长,并与高度免疫功能低下的鼠株的肠毒素血症有关,因此可能是禁忌的。溶菌酶是从噬菌体中获得的裂解酶,是治疗细菌病的新型抗菌剂。溶菌酶的优点是其靶向特异性,最小化可能影响宿主或移植肿瘤生物学的非靶向并发症。本研究的目的是鉴定针对的溶菌酶。通过使用丝裂霉素 C 对 3 个分离株中的潜伏前噬菌体进行化学激活,通过噬菌斑测定和透射电子显微镜检查并未导致噬菌体诱导。作为替代方法,针对其他细菌物种(包括密切相关的物种 )的 8 种溶菌酶被测试对 的裂解作用,但没有成功。这些发现与先前报道的 21 个分离株的基因组分析结果一致,该分析使用 PHAST 和 PHASTER 网络服务器工具未能揭示噬菌体序列。根据这些结果,我们建议 是那些缺乏溶原噬菌体的稀有细菌物种之一,因此鉴定针对的溶菌酶更具挑战性。然而,可能是研究抗噬菌体系统影响的有用模型生物。