Barker J, Brown M R
Department of Biomedical Sciences, Sheffield Hallam University, UK.
J Antimicrob Chemother. 1995 Jul;36(1):7-21. doi: 10.1093/jac/36.1.7.
It is not clear how Legionella pneumophila, which is a ubiquitous aquatic organism not possessing a mammalian reservoir, evolved the ability to cause human disease. The unusual ecology of the organism may play an important role in the transmission and virulence of legionella infections. L. pneumophila can infect and kill specific species of free-living amoebae as well as multiplying as an intracellular parasite in human phagocytic cells. In nature L. pneumophila can survive and possibly replicate in free suspension, and grow in biofilms and in protozoa thus leading to diverse phenotypes, potentially with diverse virulence and susceptibility properties. Indeed, recent evidence shows that intra-amoeba growth induces a phenotype that is dramatically different physiologically to that obtained in vitro, with altered virulence and susceptibility properties. Growth in macrophages also has profound effect on the physiological properties of L. pneumophila. Many different stress proteins are expressed by the organism as a result of intra-macrophage growth. A heat shock protein is abundantly synthesised and may be presented on the surface of infected macrophages, which allows them to be targeted by T-lymphocytes for destruction. The difficulties in successfully treating Legionnaires' disease are probably influenced by the intracellular location of L. pneumophila. Retrospective clinical studies show that it is only drugs such as erythromycin, ciprofloxacin and rifampicin, which are capable of accumulating in phagocytic cells, that are efficacious in the treatment of legionnaires' disease. Despite the use of such drugs treatment failures occur, but these do not appear to be associated with the emergence of resistant strains. Studies have shown that although erythromycin and rifampicin can inhibit the multiplication of L. pneumophila in macrophages the organism is not killed and can resume multiplying when the drugs are removed. Thus a competent cell mediated immune response is important in recovery from legionella infections. There is an urgent need for greater understanding of how the changes induced by intracellular growth affect sensitivity to antibiotics and of how the changes induced by intracellular growth affect sensitivity to antibiotics and host defences. Immunocompromised patients, who have the highest mortality rates, are likely to gain the most from progress in the treatment of L. pneumophila infections.
嗜肺军团菌是一种普遍存在于水生环境中的微生物，并无哺乳动物宿主，但它如何进化出导致人类疾病的能力尚不清楚。该微生物独特的生态环境可能在军团菌感染的传播及毒力方面发挥重要作用。嗜肺军团菌既能感染并杀死特定种类的自由生活阿米巴，也能在人类吞噬细胞内作为细胞内寄生虫进行繁殖。在自然环境中，嗜肺军团菌能够在自由悬浮状态下存活甚至可能进行复制，还能在生物膜和原生动物中生长，从而导致多种表型，其毒力和易感性可能各不相同。事实上，最近的证据表明，在阿米巴内生长会诱导出一种生理上与体外培养截然不同的表型，其毒力和易感性特性也会发生改变。在巨噬细胞内生长对嗜肺军团菌的生理特性也有深远影响。由于在巨噬细胞内生长，该微生物会表达许多不同的应激蛋白。一种热休克蛋白会大量合成，并可能呈现在被感染巨噬细胞的表面，这使得它们成为T淋巴细胞攻击破坏的目标。成功治疗军团病的困难可能受到嗜肺军团菌细胞内定位的影响。回顾性临床研究表明，只有诸如红霉素、环丙沙星和利福平这类能够在吞噬细胞内蓄积的药物，才对治疗军团病有效。尽管使用了这类药物，但仍会出现治疗失败的情况，不过这些情况似乎与耐药菌株的出现无关。研究表明，虽然红霉素和利福平能够抑制嗜肺军团菌在巨噬细胞内的繁殖，但该微生物并未被杀死，当药物去除后它又能恢复繁殖。因此，有效的细胞介导免疫反应对于从军团菌感染中康复很重要。迫切需要更深入了解细胞内生长所诱导的变化如何影响对抗生素的敏感性，以及这些变化如何影响对抗生素和宿主防御的敏感性。免疫功能低下的患者死亡率最高，他们可能会从嗜肺军团菌感染治疗的进展中获益最多。
