Mascellino M T, Farinelli S, Iegri F, Iona E
Department of Infectious and Tropical Diseases, La Sapienza University, Rome, Italy.
New Microbiol. 1998 Jan;21(1):31-40.
The 4-Quinolones are known to induce the SOS response. This should also be the case with AZT (Zidovudine) which has the same bactericidal mechanism. SOS response might make the bacteria more sensitive or more resistant to subsequent doses of quinolones and AZT. NA (Nalidixic acid), the first quinolone of the early 1960s, sensitises a strain of E. coli isolated from the urine of patients with cystopyelitis and the E. coli AB1157 wild type strain which is a well-known SOS inducer. In this case, the SOS system is not involved but only the recombination repair mechanisms which make the bacteria more susceptible to further damage by NA. On the contrary, CPX (Ciprofloxacin) protects E. coli from further exposure to antibiotics. Therefore the SOS response induction assists the bacteria in recovering from the DNA damage caused by CPX. The SOS response induced by AZT in the tested E. coli strains does not seem to either contribute to the lethality of the drug or to be involved in protecting bacteria from the damage caused by AZT. In fact, the percentage of killing was the same for both pre-treated and non pre-treated bacteria (p = 0.5). On the contrary, it was found that in Salmonella typhimurium belonging to blood of a patient with recurrent bacteriaemia, the CPX added to pre-treated bacteria with AZT was less lethal than when it was added to non pre-treated bacteria. The SOS response, in this case, protects bacteria from the damage caused by AZT.
已知4-喹诺酮类药物可诱导SOS反应。具有相同杀菌机制的齐多夫定(AZT)也应如此。SOS反应可能会使细菌对后续剂量的喹诺酮类药物和AZT更敏感或更具抗性。萘啶酸(NA)是20世纪60年代初的第一种喹诺酮类药物,它可使从膀胱炎患者尿液中分离出的大肠杆菌菌株以及作为一种著名SOS诱导剂的大肠杆菌AB1157野生型菌株敏感。在这种情况下,不涉及SOS系统,仅涉及重组修复机制,该机制使细菌更容易受到NA的进一步损伤。相反,环丙沙星(CPX)可保护大肠杆菌免受进一步接触抗生素的影响。因此,SOS反应的诱导有助于细菌从CPX引起的DNA损伤中恢复。在测试的大肠杆菌菌株中,AZT诱导的SOS反应似乎既不会导致药物的致死性,也不会参与保护细菌免受AZT造成的损伤。事实上,预处理和未预处理细菌的杀灭率相同(p = 0.5)。相反,发现在一名复发性菌血症患者血液中的鼠伤寒沙门氏菌中,添加到用AZT预处理细菌中的CPX比添加到未预处理细菌中的致死性更低。在这种情况下,SOS反应可保护细菌免受AZT造成的损伤。