Kimmitt P T, Harwood C R, Barer M R
The Medical School, University of Newcastle, Newcastle upon Tyne, United Kingdom.
Emerg Infect Dis. 2000 Sep-Oct;6(5):458-65. doi: 10.3201/eid0605.000503.
Toxin synthesis by Shiga toxin-producing Escherichia coli (STEC) appears to be coregulated through induction of the integrated bacteriophage that encodes the toxin gene. Phage production is linked to induction of the bacterial SOS response, a ubiquitous response to DNA damage. SOS-inducing antimicrobial agents, particularly the quinolones, trimethoprim, and furazolidone, were shown to induce toxin gene expression in studies of their effects on a reporter STEC strain carrying a chromosome-based stx2::lacZ transcriptional fusion. At antimicrobial levels above those required to inhibit bacterial replication, these agents are potent inducers (up to 140-fold) of the transcription of type 2 Shiga toxin genes (stx2); therefore, they should be avoided in treating patients with potential or confirmed STEC infections. Other agents (20 studied) and incubation conditions produced significant but less striking effects on stx2 transcription; positive and negative influences were observed. SOS-mediated induction of toxin synthesis also provides a mechanism that could exacerbate STEC infections and increase dissemination of stx genes. These features and the use of SOS-inducing antibiotics in clinical practice and animal husbandry may account for the recent emergence of STEC disease.
产志贺毒素大肠杆菌（STEC）的毒素合成似乎是通过诱导编码毒素基因的整合噬菌体来共同调节的。噬菌体的产生与细菌SOS应答的诱导有关，SOS应答是对DNA损伤的一种普遍反应。在对携带基于染色体的stx2::lacZ转录融合的报告STEC菌株的作用研究中，SOS诱导型抗菌剂，特别是喹诺酮类、甲氧苄啶和呋喃唑酮，被证明可诱导毒素基因表达。在高于抑制细菌复制所需的抗菌水平时，这些药物是2型志贺毒素基因（stx2）转录的强效诱导剂（高达140倍）；因此，在治疗潜在或确诊的STEC感染患者时应避免使用。其他药物（研究了20种）和培养条件对stx2转录产生了显著但不太明显的影响；观察到了正向和负向影响。SOS介导的毒素合成诱导也提供了一种可能加剧STEC感染并增加stx基因传播的机制。这些特征以及SOS诱导型抗生素在临床实践和畜牧业中的使用可能解释了STEC疾病最近的出现。
