Mandelbaum-Shavit F, Barak V, Saheb-Tamimi K, Grossowicz N
Department of Bacteriology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Antimicrob Agents Chemother. 1991 Dec;35(12):2526-30. doi: 10.1128/AAC.35.12.2526.
Indole-3-propionic acid (IPA), a phytohormone derivative, is a potent inhibitor of growth of Legionella pneumophila cultivated extracellularly in a chemically defined hypotonic medium and intracellularly in human monocytes. The inhibitory activity turns into bactericidal activity with increasing concentrations. The susceptibility of the microorganism to IPA was more evident in "fast-growing" cultures (under conditions of vigorous shaking) than in static cultures growing under an atmosphere of 5% CO2-95% air, which resulted in a decreased growth rate. The MIC, after incubation with the drug for 48 h and as determined by counting of the CFU, was 1.58 microM for fast-growing cultures and 2.64 microM for those grown under static conditions. The MBCs were 5.28 and 26.43 microM, respectively. Tryptophan (Trp) at 150 microM prevented the inhibition caused by 2.64 microM IPA, increased the MIC about 3-fold, and increased the MBC by 10-fold. The effect of Trp was less remarkable in "slow-growing" cultures. The susceptibility of L. pneumophila proliferating in human monocytes was markedly lower than that when it was cultivated extracellularly in the chemically defined hypotonic medium. The MIC after incubation for 48 h was 5.28 microM, and a decrease in viable count was achieved with 105.70 microM. The lower susceptibility was apparently due (at least partially) to the presence of Trp (24.50 microM) in the RPMI 1640 medium that was used for the monocyte cultures. The effect of IPA was time dependent, and prolonged exposure enhanced the bactericidal activity and turned the inhibitory dose into a bactericidal dose. The present data demonstrate that IPA is a potent anti-L. pneumophila factor, although it has a markedly lower activity against bacteria growing intracellularly compared with its activity against extracellularly proliferating microorganisms.
吲哚 - 3 - 丙酸（IPA）是一种植物激素衍生物，是嗜肺军团菌在化学成分明确的低渗培养基中细胞外培养以及在人单核细胞内细胞内培养时生长的强效抑制剂。随着浓度增加，其抑制活性转变为杀菌活性。该微生物对IPA的敏感性在“快速生长”培养物（剧烈振荡条件下）中比在5％CO2 - 95％空气气氛下生长的静态培养物中更明显，后者导致生长速率降低。与药物孵育48小时后，通过计数CFU确定，快速生长培养物的MIC为1.58 microM，静态条件下生长的培养物的MIC为2.64 microM。MBC分别为5.28和26.43 microM。150 microM的色氨酸（Trp）可防止2.64 microM IPA引起的抑制作用，使MIC增加约3倍，并使MBC增加10倍。Trp在“缓慢生长”培养物中的作用不太明显。在人单核细胞中增殖的嗜肺军团菌的敏感性明显低于其在化学成分明确的低渗培养基中细胞外培养时的敏感性。孵育48小时后的MIC为5.28 microM，105.70 microM时可实现活菌数减少。较低的敏感性显然（至少部分）归因于用于单核细胞培养的RPMI 1640培养基中存在Trp（24.50 microM）。IPA的作用是时间依赖性的，延长暴露可增强杀菌活性，并将抑制剂量转变为杀菌剂量。目前的数据表明，IPA是一种强效的抗嗜肺军团菌因子，尽管与细胞外增殖微生物相比，其对细胞内生长细菌的活性明显较低。
