INTRAPHAGOCYTIC GROWTH INDUCES AN ANTIBIOTIC-RESISTANT PHENOTYPE OF LEGIONELLA-PNEUMOPHILA
INTRAPHAGOCYTIC GROWTH INDUCES AN ANTIBIOTIC-RESISTANT PHENOTYPE OF LEGIONELLA-PNEUMOPHILA
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DOI：
10.1128/aac.39.12.2684
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发表时间：
1995-12-01
影响因子：
4.9
通讯作者：
BROWN, MRW
中科院分区：
文献类型：
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作者：
BARKER, J;SCAIFE, H;BROWN, MRW
研究了在U937人单核细胞或多噬阿米巴中生长的嗜肺军团菌分离株从宿主细胞中释放后的抗菌活性。仅在体外生长的嗜肺细胞在每毫升5 μ g利福平下6小时后至少杀死99.9%，24小时后没有可检测到的存活细胞。通过暴露于环丙沙星测试，在体外生长的细胞中观察到类似的杀伤率。相反，时间-存活研究表明，巨噬细胞生长的细胞和阿米巴生长的细胞对两种药物的活性的抗性高约1，000倍。用每毫升5 μ g利福平处理的巨噬细胞生长的细胞在6和24小时后分别显示70%和62%的存活率。细胞内生长的军团菌对红霉素也具有高度抗性（8 μ g/ml）。在暴露于药物24小时后，阿米巴生长的和巨噬细胞生长的军团菌分别有70%和60%的存活率，而在体外生长的细胞显示活细胞计数减少2-log（10）。将嗜肺军团菌细胞在肉汤中传代培养48小时，它们恢复到体外生长的表型特征。在形态学上，细胞比它们在细胞内生长的对应物大，并且丧失了抗性特征。传代培养的细胞对所有三种药物的亲和性与仅在体外生长的军团菌细胞的亲和性相似。鉴于这些发现，军团病的成功治疗可能与巨噬细胞内生长诱导的抗性表型以及抗生素进入吞噬细胞的能力有关。
The antimicrobial susceptibilities of Legionella pneumophila isolates grown either in U937 human monocytic cells or in Acanthamoeba polyphaga were studied after release from the host cells without further subculture, Time-survival studies showed that exposure of L. pneumophila cells, grown exclusively in vitro, to 5 mu g of rifampin per ml resulted in at least 99.9% killing after 6 h and no detectable survivors at 24 h. Similar rates of killing were observed for in vitro-grown cells tested by exposure to ciprofloxacin, Conversely, time-survival studies revealed that macrophage-grown and amoeba-grown cells were ca, 1,000-fold more resistant to the activities of both drugs, Macrophage-grown cells treated with 5 mu g of rifampin per mi showed 70 and 62% survival after 6 and 24 h, respectively, Intracellularly grown legionellae were also highly resistant to erythromycin (8 mu g/ml). After 24 h of exposure to the drug, there was 70 and 60% survival for amoeba-grown and macrophage-grown legionellae, respectively, whereas in vitro-grown cells showed a 2-log(10) reduction in viable count, When intracellularly grown L. pneumophila cells were subcultured in broth for 48 h, they reverted to the phenotype characteristic of in vitro growth, Morphologically, the cells were larger than their intracellularly grown counterparts and resistance characteristics were lost, The susceptibilities of the subcultured cells to all three drugs were similar to those of Legionella cells grown exclusively in vitro, In view of these findings, the successful treatment of Legionnaires' disease may be related as much to the resistance phenotype induced by intramacrophage growth as to the ability of the antibiotic to enter phagocytic cells.