Cloning gen uvrB, operon Moa and requirement of clomplex UvrABC during quinolones mutagenesis in Salmonella typhimurium (∆uvrB y∆moaA-E) strains

Abstract

Given the clinic importance of the quinolones in the control of infectious diseases and their possible involvement in the bacterial mutagenesis, this study has been focused to gain insight into the mutagenesis mechanisms using ciprofloxacin as a model. In reference to the mutagenic mechanisms, it has been shown that bacteria must own a functional nucleotide excision repair system (NER) for taking part the ciprofloxacin-induced mutagenesis. Furthermore, it has been rule out that moa operon, which codifies genes participating in the biosynthesis of molybdenum cofactors, has a role in such mutagenesis process. These results support early studies which suggested the participation of NER in the above mentioned mutagenesis and indicate that likely other deleted genes apart from uvrB in the tester strains TA104 and TA2659 of Salmonella typhimurium may not have an important role in the quinolones mediated mutagenesis. All these results together indicate that quinolones have to produce different kinds of DNAlesions in bacterial cells. Thus the interaction of quinolone molecule with the DNA-DNA gyrase complex has to generate a type of distortion analogue to an interchain bond, giving rise to a premutagenic lesion. This lesion can be processed by the NER system and become a mutagenic lesion that could be bypassed by an error-prone DNA polymerase (as MucAB) introducing a mutation. Such mutagenic mechanism has to be common to that kind of molecules. Having in mind this results the possible implications of the pathogen population exposition to low doses of quinolones is discussed, and it is proposed that these studies are key for the development of new quinolone molecules, which should present both a higher antibacterial and a low capability of mutagenic activities.