Different Classes of Antibiotics Differentially Influence Shiga Toxin Production
Different Classes of Antibiotics Differentially Influence Shiga Toxin Production
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DOI：
10.1128/aac.01783-09
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发表时间：
2010-09-01
影响因子：
4.9
通讯作者：
Weiss, Alison Ann
中科院分区：
文献类型：
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作者：
McGannon, Colleen Marie;Fuller, Cynthia Ann;Weiss, Alison Ann
志贺毒素(STX)是大肠杆菌O157：H7中的一种晚期基因产物，由整合到染色体上的温和型噬菌体编码。噬菌体晚期基因，包括STX，在溶原性状态下是沉默的。然而，胁迫信号，包括一些由抗生素诱导的信号，触发噬菌体进入裂解周期，噬菌体复制和STX产生同时发生。除了O157：H7产生的STX外，O157：H7产生的噬菌体还可以感染无害的肠道大肠杆菌，并招募它们产生志贺毒素。为了了解抗生素如何影响STX的产生，在有或没有噬菌体敏感的大肠杆菌的情况下，用不同种类的抗生素处理STX溶原菌，并用表达荧光素酶的Vero细胞监测STX对蛋白质合成的抑制。生长抑制水平的抗生素抑制了STX的产生。针对DNA合成的抗生素，包括环丙沙星(CIP)和新诺明-磺胺甲恶唑，其亚抑制水平增加了STX的产生，而针对细胞壁、转录或翻译的抗生素则没有。大肠杆菌O157：H7在噬菌体敏感的大肠杆菌存在下培养时产生的STX比单纯培养时更多。值得注意的是，即使在CIP完全抑制O157：H7的生长的情况下，也检测到非常高水平的STX。相比之下，即使在O157：H7活性保持较高的情况下，阿奇霉素也显著降低了STX水平。
Shiga toxin (Stx) in Escherichia coli O157:H7 is encoded as a late gene product by temperate bacteriophage integrated into the chromosome. Phage late genes, including stx, are silent in the lysogenic state. However, stress signals, including some induced by antibiotics, trigger the phage to enter the lytic cycle, and phage replication and Stx production occur concurrently. In addition to the Stx produced by O157:H7, phage produced by O157:H7 can infect harmless intestinal E. coli and recruit them to produce Shiga toxin. To understand how antibiotics influence Stx production, Stx lysogens were treated with different classes of antibiotics in the presence or absence of phage-sensitive E. coli, and Stx-mediated inhibition of protein synthesis was monitored using luciferase-expressing Vero cells. Growth-inhibitory levels of antibiotics suppressed Stx production. Subinhibitory levels of antibiotics that target DNA synthesis, including ciprofloxacin (CIP) and trimethoprim-sulfamethoxazole, increased Stx production, while antibiotics that target the cell wall, transcription, or translation did not. More Stx was produced when E. coli O157:H7 was incubated in the presence of phage-sensitive E. coli than when grown as a pure culture. Remarkably, very high levels of Stx were detected even when growth of O157:H7 was completely suppressed by CIP. In contrast, azithromycin significantly reduced Stx levels even when O157:H7 viability remained high.