Modulation of Salmonella gene expression by subinhibitory concentrations of quinolones

Yim, Grace; McClure, Jo-Ann; Surette, Michael G.; Davies, Julian

doi:10.1038/ja.2010.137

Cited by 50 publications

(36 citation statements)

References 46 publications

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“…CPR and related fluoroquinolones, such as norfloxacin, induce mutations in a dose-dependent manner in several bacterial systems, including Salmonella enterica serovar Typhimurium (3,6,10,11,13,14), E. coli (2,4,9), Streptococcus pneumoniae (8), S. aureus (5), Pseudomonas aeruginosa (12), and Mycobacterium fortuitum (7), although the level of mutagenesis (3-to 10-fold) is well below that for standard mutagens, with the exception of M. fortuitum (7). For example, Rif r in E. coli is increased 5,800-fold by alkylating agents, such as ethyl methanesulfonate (EMS) (19); 400-fold by UV light irradiation (19); and 150-fold and 4,800-fold by the base analogs 2-aminopurine and 5-bromodeoxyuridine, respectively (19,35).…”

Section: Discussionmentioning

confidence: 99%

“…This allows us to separate effects of CPR itself from those emanating from the CPR-induced processes. Treatment with CPR leads to complex changes in cellular metabolism and double-strand breaks (24) that result in the induction of the SOS system (1,3,10,13,25,26). In fact, CPR can induce the SOS system to higher levels than UV irradiation (J. H. Miller, unpublished data).…”

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“…In particular, ciprofloxacin (CPR) and its close derivative norfloxacin (NOR) display mutagenic activity in different detector systems (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). The mutagenic properties can result in an increase in the appearance of resistant mutants (1,2,4,5).…”

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“…everal bactericidal antibiotics have been reported to have low to moderate mutagenic activity when used at subinhibitory or sublethal concentrations (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14), usually ranging from 3-to 8-fold over background levels of spontaneous mutations (with one exception [7]). In particular, ciprofloxacin (CPR) and its close derivative norfloxacin (NOR) display mutagenic activity in different detector systems (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14).…”

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Mutational Consequences of Ciprofloxacin in Escherichia coli

Song

Goff

Davidian

et al. 2016

Antimicrob Agents Chemother

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We examined the mutagenic specificity of the widely used antibiotic ciprofloxacin (CPR), which displays weak to moderate mutagenic activity in several bacteria and generates short in-frame deletions in rpoB in Staphylococcus aureus. To determine the spectrum of mutations in a system where any gene knockout would result in a recovered mutant, including frameshifts and both short and long deletions, we examined CPR-induced mutations in the thymidylate synthase-encoding thyA gene. Here, any mutation resulting in loss of thymidylate synthase activity generates trimethoprim (Trm) resistance. We found that deletions and insertions in all three reading frames predominated in the spectrum. They tend to be short deletions and cluster in two regions, one being a GC-rich region with potential extensive secondary structures. We also exploited the well-characterized rpoB-Rif r system in Escherichia coli to determine that cells grown in the presence of sublethal doses of CPR not only induced short inframe deletions in rpoB, but also generated base substitution mutations resulting from induction of the SOS system. Some of the specific point mutations prominent in the spectrum of a strain that overproduces the dinB-encoded Pol IV were also present after growth in CPR. However, these mutations disappeared in CPR-treated dinB mutants, whereas the deletions remained. Moreover, CPR-induced deletions also occurred in a strain lacking all three SOS-induced polymerases. We discuss the implications of these findings for the consequences of overuse of CPR and other antibiotics. Several bactericidal antibiotics have been reported to have low to moderate mutagenic activity when used at subinhibitory or sublethal concentrations (1-14), usually ranging from 3-to 8-fold over background levels of spontaneous mutations (with one exception [7]). In particular, ciprofloxacin (CPR) and its close derivative norfloxacin (NOR) display mutagenic activity in different detector systems (1-14). The mutagenic properties can result in an increase in the appearance of resistant mutants (1, 2, 4, 5). A previous study of CPR-induced mutations in the rpoB gene of Staphylococcus aureus detected short in-frame deletions (5). However, the rpoB system cannot detect out-of-frame deletions or insertions or in-frame deletions or insertions of more than 21 bp, since the integrity of the RNA polymerase must remain intact. Here, we have undertaken a study of the types of mutations resulting from treatment with CPR in Escherichia coli using the thyATrm r system, which detects trimethoprim (Trm)-resistant mutants that result from any mutations inactivating the thyA gene (15), including large or small deletions or additions, both in frame and out of frame. We also used the E. coli rpoB-Rif r system, which monitors mutations leading to rifampin (Rif) resistance (16-23), since the system is so extensively characterized that the spectra of different mutagenic pathways leave telltale fingerprints. This allows us to separate effects of CPR itself from those emanating from the ...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Mutational Consequences of Ciprofloxacin in Escherichia coli

Song

Goff

Davidian

et al. 2016

Antimicrob Agents Chemother

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“…As it was performed in the previous study, sub-MIC concentrations of tobramycin-induced Pseudomonas aeruginosa biofilm formation through a mechanism that involves the intracellular second messenger cyclic dimeric guanosine monophosphate (c-di-GMP) [34]. Other researchers have studied the modulation of Salmonella gene expression by sub-MIC concentrations of quinolones [35]. Even at the sub-MICs employed, all tested fluoroquinolones upregulated genes involved in the SOS response, umuD, LexA, sbmC and dinP.…”

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Effects of sub-MIC antibiotic concentrations on biofilm production of Salmonella Infantis

Tezel

Akçelik

Yüksel

et al. 2016

Biotechnology & Biotechnological Equipment

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In the present study, 13 Salmonella Infantis strains, which have been originated from Turkey, were selected due to their clinical and industrial relevance, sufficient biofilm producing capability and multidrug resistance. Although all tested strains were built up of thin pellicle, optimum pellicle formation has occurred at 28 C. All S. Infantis biofilms were categorized as 'bdar' morphotype following the incubation at both 20 and 28 C, while they were categorized as 'saw' morphotype at 37 C. Under a certain incubation temperature (28 C), 84.62% of strains have formed strong biofilm structures. By using the disk diffusion method, high levels of resistance have been observed among tested bacteria against nalidixic acid (100%), spectinomycin (100%), streptomycin (92.3%), tetracycline (92.3%), kanamycin (76.9%) and neomycin (76.9%). Further studies were performed with S. Infantis DMC 12 strain, due to its capability to produce biofilm and multidrug resistance phenotype. Gentamycin (>64 mg/mL, 2 £ MIC) and tetracycline (>128 mg/mL, 4 £ MIC) were determined as the most effective antibiotics against biofilm formation. The biofilm forms have showed increased antimicrobial resistance when it was compared to the planktonic bacteria. The highest resistance rates of the biofilm bacteria were observed to neomycin (12 £ MIC) followed by spectinomycin (10 £ MIC) and streptomycin (10 £ MIC). Biofilm structure was induced as a result of nalidixic acid, spectinomycin, tetracycline and neomycin treatment at sub-MIC concentrations of tested antibiotics.

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