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噬菌体:具有前景的抗菌剂?

Bacteriophages: antibacterials with a future?

作者信息

Broxmeyer Lawrence

机构信息

Med-America Research, 148-14A Eleventh Avenue, Whitestone, NY 11357, USA.

出版信息

Med Hypotheses. 2004;62(6):889-93. doi: 10.1016/j.mehy.2004.02.002.

Abstract

The hypothesis as to whether a benign species of bacteria could kill a virulent kind has to this point been untested. Recently it was shown that in the macrophage, bacteriophages, when properly introduced through a nonvirulent microbe, had a killing rate for virulent AIDS Mycobacterium tuberculosis and Mycobacterium avium far in excess of modern day antibiotics. The study in effect brought a natural phenomena, lysogeny, whereby one bacterial colony kills another thru phage weaponry, to bear in the conquest of hard-to-kill, antibiotic resistant pathogens. This killing occurred intracellularly, within the white blood cell using Mycobacterium smegmatis, a benign bacterial species found generally in smegma secretions from human genitalia as well as soil, dust and water, and first identified in 1884. The subsequent treatment of M. avium-infected, as well as M. tuberculosis-infected RAW 264.7 macrophages, with M. smegmatis transiently infected with TM4 resulted in a unexpectedly large time- and titer-dependent reduction in the number of viable intracellular bacilli. In addition, the M. smegmatis vacuole harboring TM4 fused with the M. avium vacuole in macrophages. These results suggested a potentially novel concept to kill intracellular pathogenic bacteria and warrant future development.

摘要

关于一种良性细菌是否能杀死一种毒性较强的细菌这一假说,到目前为止尚未得到验证。最近有研究表明,在巨噬细胞中,当通过一种无毒微生物适当引入噬菌体时,其对毒性较强的艾滋病结核分枝杆菌和鸟分枝杆菌的杀灭率远远超过了现代抗生素。实际上,这项研究揭示了一种自然现象——溶原现象,即一个细菌菌落通过噬菌体武器杀死另一个细菌菌落,从而用于攻克难以杀灭的、具有抗生素抗性的病原体。这种杀灭发生在细胞内,即在白细胞内,使用耻垢分枝杆菌,这是一种通常在人类生殖器的包皮垢分泌物以及土壤、灰尘和水中发现的良性细菌物种,于1884年首次被鉴定出来。随后,用短暂感染了TM4的耻垢分枝杆菌对感染鸟分枝杆菌以及感染结核分枝杆菌的RAW 264.7巨噬细胞进行处理,结果导致存活的细胞内杆菌数量出现了意外的、与时间和滴度相关的大幅减少。此外,含有TM4的耻垢分枝杆菌液泡在巨噬细胞中与鸟分枝杆菌液泡融合。这些结果提示了一种潜在的杀死细胞内致病细菌的新观念,值得未来进一步研究。

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