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Searching for a Bacteriophage Lysin to Treat Corynebacterium bovis in Immunocompromised Mice

机译:寻找溶菌液体蛋白在免疫染色的小鼠中治疗棒状杆菌

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摘要

Corynebacterium bovis is the causative agent of Corynebacterium-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 administrationof 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 Clostridioides difficile enterotoxemia in highly immunocompromisedmurine 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 engraftedtumor. The aim of this study was to identify lysins active against C. bovis. Chemical activation of latent prophages by using mitomycin C in 3 C. bovis isolates did not cause bacteriophage induction as determined through plaque assays and transmission electron microscopy. Asan alternative approach, 8 lysins associated with other bacterial species, including those from the closely related species C. falsenii, were tested for their lytic action against C. bovis but were unsuccessful. These findings were congruent with the previously reported genomicanalysis of 21 C. bovis isolates, which failed to reveal bacteriophage sequences by using the PHAST and PHASTER web server tools. From these results, we suggest C. bovis is among those rare bacterial species devoid of lysogenic bacteriophages, thus making the identification ofC. bovis-specific lysins more challenging. However, C. bovis may be a useful model organism for studying the effects of antiphage systems.
机译:Bovis植物杆菌是免疫组织小鼠的源于棒状杆菌相关高诊断病的致病因子。由此产生的皮肤病理可以深刻,并且可以与严重的浪费有关,使这些动物不适合研究。虽然抗生素的施用有效解决临床症状,但抗生素不会消除违规细菌。此外,可以禁止抗生素使用,因为它可以影响肿瘤生长,并且与高度免疫中心菌株中的梭菌梭菌腹菌肠毒性有关。作为从噬菌体获得的裂解酶的裂解丝,是用于治疗细菌疾病的新型抗微生物剂。裂解蛋白的优点是其目标特异性,具有最小的偏移并发症,其可能影响宿主或生物移植料的生物学。本研究的目的是鉴定催氨酸激活对抗C. Bovis。通过使用丝霉素C在3℃下的潜血管蛋白CIN的化学活化。BOVIS分离物未引起通过斑块测定和透射电子显微镜测定的噬菌体诱导。 ASAN替代方法,8种与其他细菌物种相关的8次裂解蛋白,包括来自密切相关的物种C. falsenii的裂解,对抗C. Bovis进行裂解作用,但不成功。这些发现与先前报告的Genomicanal分析21℃的肉毒杆菌分析,这未能通过使用Phast和Phaster Web服务器工具揭示噬菌体序列。从这些结果来看,我们建议Bovis是那些稀有细菌种类缺乏溶血性噬菌体的,从而使鉴定鉴定。 Bovis特异性Lysins更具挑战性。然而,C.Bovis可能是用于研究抗灰系统影响的有用模型生物体。

著录项

  • 来源
    《Comparative Medicine》 |2020年第4期|共8页
  • 作者单位

    Tri-Institutional Training Program in Laboratory Animal Medicine and Science Memorial Sloan Kettering Cancer Center Weill Cornell Medicine and The Rockefeller University;

    Laboratory of Bacterial Pathogenesis and Immunology The Rockefeller University;

    Department of Pathology and Laboratory Medicine Weill Cornell Medicine;

    Tri-Institutional Training Program in Laboratory Animal Medicine and Science Memorial Sloan Kettering Cancer Center Weill Cornell Medicine and The Rockefeller University;

    Laboratory of Bacterial Pathogenesis and Immunology The Rockefeller University;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 畜牧、动物医学、狩猎、蚕、蜂;
  • 关键词

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