Mutation Frequency

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Dan I Andersson - One of the best experts on this subject based on the ideXlab platform.

  • Mutation Frequency and biological cost of antibiotic resistance in helicobacter pylori
    Proceedings of the National Academy of Sciences of the United States of America, 2001
    Co-Authors: Britta Bjorkholm, Maria Sjolund, Per Falk, Otto G Berg, Lars Engstrand, Dan I Andersson
    Abstract:

    Abstract Among the several factors that affect the appearance and spread of acquired antibiotic resistance, the Mutation Frequency and the biological cost of resistance are of special importance. Measurements of the Mutation Frequency to rifampicin resistance in Helicobacter pylori strains isolated from dyspeptic patients showed that ≈1/4 of the isolates had higher Mutation frequencies than Enterobacteriaceae mismatch-repair defective mutants. This high Mutation Frequency could explain why resistance is so frequently acquired during antibiotic treatment of H. pylori infections. Inactivation of the mutS gene had no substantial effect on the Mutation Frequency, suggesting that MutS-dependent mismatch repair is absent in this bacterium. Furthermore, clarithromycin resistance conferred a biological cost, as measured by a decreased competitive ability of the resistant mutants in mice. In clinical isolates this cost could be reduced, indicating that compensation is a clinically relevant phenomenon that could act to stabilize resistant bacteria in a population.

  • Mutation Frequency and biological cost of resistance in Helicobacter pylori.
    2001
    Co-Authors: Britta Bjorkholm, Maria Sjolund, Per Falk, Otto G Berg, Lars Engstrand, Dan I Andersson
    Abstract:

    Antibiotic resistance is of current concern. Bacteria have become increasingly resistant to commonly used antibiotics and we are facing a growing resistance problem. The present thesis was aimed at studying the impact of antibiotic treatment on pathogenic bacteria as well as on the normal human microbiota, with focus on resistance development.Among the factors that affect the appearance of acquired antibiotic resistance, the Mutation Frequency and biological cost of resistance are of special importance. Our work shows that the Mutation Frequency in clinical isolates of Helicobacter pylori was generally higher than for other studied bacteria such as Enterobacteriaceae; ¼ of the isolates displayed a Mutation Frequency higher than Enterobacteriaceae defective mismatch repair mutants and could be regarded as mutator strains.In H. pylori, clarithromycin resistance confers a biological cost, as measured by decreased competitive ability of the resistant mutants in mice. In clinical isolates, this cost could be reduced, consistent with compensatory evolution stabilizing the presence of the resistant phenotype in the population. Thus, compensation is a clinically relevant phenomenon that can occur in vivo.Furthermore, our results show that clinical use of antibiotics selects for stable resistance in the human microbiota. This is important for several reasons. First, many commensals occasionally can cause severe disease, even though they are part of the normal microbiota. Therefore, stably resistant populations increase the risk of unsuccessful treatment of such infections. Second, resistance in the normal microbiota might contribute to increased resistance development among pathogens by interspecies transfer of resistant determinants.

Christophe Merlin - One of the best experts on this subject based on the ideXlab platform.

  • Comparing TiO2photocatalysis and UV-C radiation for inactivation and mutant formation of Salmonella typhimurium TA102
    Environmental Science and Pollution Research, 2017
    Co-Authors: Antonino Fiorentino, Hélène Guilloteau, Xavier Bellanger, Luigi Rizzo, Christophe Merlin
    Abstract:

    Salmonellosis is one of the most common causes of foodborne bacterial human disease worldwide, and the emergence of multidrug-resistant (MDR) strains of Salmonella enterica serovar Typhimurium (S. typhimurium) was associated to the incidence of invasive salmonellosis. The objective of the present work was to investigate the effects of the TiO2 photocatalysis process in terms of both bacteria inactivation and the emergence of mutants, on S. typhimurium TA102 water suspensions. The TiO2 photocatalysis was compared with a conventional disinfection process such as UV-C radiation. In spite of the faster bacterial inactivation obtained in UV-C disinfection experiments (45, 15, and 10 min for total inactivation for initial cell density 109, 108, and 107 CFU mL−1, respectively), photocatalytic disinfection (60, 30, and 15 min) was more energy efficient because of a lower energy requirement (2--20 mWs cm−2) compared to the UV-C disinfection process (5--30 mWs cm−2). During the photocatalytic experiments, the Mutation Frequency increased up to 1648-fold compared to background level for a 108 CFU mL−1 initial bacterial density, and mutants were inactivated after 1--10-min treatment, depending on initial bacterial cell density. In UV-C disinfection experiments, the Mutation Frequency increased up to 2181-fold for a 108 CFU mL−1 initial bacterial cell density, and UV-C doses in the range of 0.5--4.8 mWs cm−2 were necessary to decrease Mutation Frequency. In conclusion, both disinfection processes were effective in the inactivation of S. typhimurium cells, and mutants released into the environment can be avoided if cells are effectively inactivated.

  • Comparing TiO_2 photocatalysis and UV-C radiation for inactivation and mutant formation of Salmonella typhimurium TA102
    Environmental Science and Pollution Research, 2017
    Co-Authors: Antonino Fiorentino, Hélène Guilloteau, Xavier Bellanger, Luigi Rizzo, Christophe Merlin
    Abstract:

    Salmonellosis is one of the most common causes of foodborne bacterial human disease worldwide, and the emergence of multidrug-resistant (MDR) strains of Salmonella enterica serovar Typhimurium ( S. typhimurium ) was associated to the incidence of invasive salmonellosis. The objective of the present work was to investigate the effects of the TiO_2 photocatalysis process in terms of both bacteria inactivation and the emergence of mutants, on S. typhimurium TA102 water suspensions. The TiO_2 photocatalysis was compared with a conventional disinfection process such as UV-C radiation. In spite of the faster bacterial inactivation obtained in UV-C disinfection experiments (45, 15, and 10 min for total inactivation for initial cell density 10^9, 10^8, and 10^7 CFU mL^−1, respectively), photocatalytic disinfection (60, 30, and 15 min) was more energy efficient because of a lower energy requirement (2–20 mWs cm^−2) compared to the UV-C disinfection process (5–30 mWs cm^−2). During the photocatalytic experiments, the Mutation Frequency increased up to 1648-fold compared to background level for a 10^8 CFU mL^−1 initial bacterial density, and mutants were inactivated after 1–10-min treatment, depending on initial bacterial cell density. In UV-C disinfection experiments, the Mutation Frequency increased up to 2181-fold for a 10^8 CFU mL^−1 initial bacterial cell density, and UV-C doses in the range of 0.5–4.8 mWs cm^−2 were necessary to decrease Mutation Frequency. In conclusion, both disinfection processes were effective in the inactivation of S. typhimurium cells, and mutants released into the environment can be avoided if cells are effectively inactivated.

Megan Hanna - One of the best experts on this subject based on the ideXlab platform.

  • colorectal cancers from distinct ancestral populations show variations in braf Mutation Frequency
    PLOS ONE, 2013
    Co-Authors: Megan Hanna, Christina Go, Christine Roden, Robert T Jones, Panisa Pochanard, Ahmed Y Javed, Awais Javed, Chandrani Mondal, Emanuele Palescandolo
    Abstract:

    It has been demonstrated for some cancers that the Frequency of somatic oncogenic Mutations may vary in ancestral populations. To determine whether key driver alterations might occur at different frequencies in colorectal cancer, we applied a high-throughput genotyping platform (OncoMap) to query 385 Mutations across 33 known cancer genes in colorectal cancer DNA from 83 Asian, 149 Black and 195 White patients. We found that Asian patients had fewer canonical oncogenic Mutations in the genes tested (60% vs Black 79% (P = 0.011) and White 77% (P = 0.015)), and that BRAF Mutations occurred at a higher Frequency in White patients (17% vs Asian 4% (P = 0.004) and Black 7% (P = 0.014)). These results suggest that the use of genomic approaches to elucidate the different ancestral determinants harbored by patient populations may help to more precisely and effectively treat colorectal cancer. Citation: Hanna MC, Go C, Roden C, Jones RT, Pochanard P, et al. (2013) Colorectal Cancers from Distinct Ancestral Populations Show Variations in

Takeo Ohnishi - One of the best experts on this subject based on the ideXlab platform.

  • Mutation Frequency of plasmid DNA and Escherichia coli following long-term space flight on Mir.
    Journal of radiation research, 2020
    Co-Authors: Akihisa Takahashi, Ken Ohnishi, Tamotsu Nakano, Akitoshi Yokota, Tsukasa Kumagai, Takeo Ohnishi
    Abstract:

    To elucidate the biological influence of space radiation, we studied the effects of long-term space flight on Mutation of the bacterial ribosomal protein L gene (rpsL). We prepared dried samples of plasmid DNA and repair-deficient and wild type cells of Escherichia (E.) coli. After a 40-day space flight on board the Russian space station Mir, the Mutation frequencies of the rpsL gene were estimated by transformation of E. coli and by assessment of conversion of rpsL wild type phenotype (SmS) to its mutant phenotype (SmR). The experimental findings indicate that Mutation frequencies of space samples were not significantly different from those of ground control samples in plasmid DNA and both E. coli strains. It may suggest that space radiation did not influence Mutation Frequency.

  • Mutation Frequency of Plasmid DNA and Escherichia coli Following Long-term Space Flight on Mir
    Journal of Radiation Research, 2002
    Co-Authors: Akihisa Takahashi, Ken Ohnishi, Tamotsu Nakano, Akitoshi Yokota, Tsukasa Kumagai, Takeo Ohnishi
    Abstract:

    Mutation / Space radiation / Space flight / Mir To elucidate the biological influence of space radiation, we studied the effects of long-term space flight on Mutation of the bacterial ribosomal protein L gene (rpsL). We prepared dried samples of plasmid DNA and repair-deficient and wild type cells of Escherichia (E.) coli. After a 40-day space flight on board the Russian space station Mir, the Mutation frequencies of the rpsL gene were estimated by transformation of E. coli and by assessment of conversion of rpsL wild type phenotype (Sm S ) to its mutant phenotype (Sm R ). The experimental findings indicate that Mutation frequencies of space samples were not significantly different from those of ground control samples in plasmid DNA and both E. coli strains. It may suggest that space radiation did not influence Mutation Frequency.

  • Mutation Frequency of Dictyostelium discoideum spores exposed to the space environment
    Biological Sciences in Space, 1997
    Co-Authors: Akihisa Takahashi, Ken Ohnishi, Mitsuyo Fukui, Tamotsu Nakano, Katsumi Yamaguchi, Shunji Nagaoka, Takeo Ohnishi
    Abstract:

    Two strains of cellular slime mold Dictyostelium discoideum, a radiosensitive mutant and the parental wild-type strain, were used to investigate the effects of cosmic radiation on viability and Mutation Frequency at the spore stage for about 9 days in Space Shuttle of NASA. We measured little effect of space environment on viability and cell growth in the both strains as compared to ground controls. The Mutation Frequency of the flown spores were similar to that of ground control. These results suggest that there could be no effect of cosmic radiation, containing high linear energy transfer radiation at about 0.9 mSv/day as detected by real-time radiation monitoring device on the induction of Mutation at the spore stage.

  • Cancer risk in space due to radiation assessed by determining cell lethality and Mutation frequencies of prokaryotes and a plasmid during the Second International Microgravity Laboratory (IML-2) space shuttle experiment
    Oncology Reports, 1997
    Co-Authors: Kazuki Harada, Takeo Ohnishi, Yurino Obiya, Michisuke Kawashima, Takahito Miki, Yasuhiko Kobayashi, Kumio Okaichi, Tatsuo Nakano, Hiroshi Watanabe, Chiaki Mukai
    Abstract:

    We participated in a space experiment conducted during the 2nd International Microgravity Laboratory Mission (IML-2) project. The aim of our study was to investigate the effects of space radiation, i.e., high-LET (linear energy transfer) cosmic radiation, on living organisms in the 'Realtime Radiation Monitoring Device (RRMD)'. The biological samples, dried E. coli DNA repair-deficient mutant cells and shuttle vector plasmid pZl89 DNA, were prepared and placed in a biospecimen box sandwiched between 'Harzlas' plastic radiation detectors. This box was then loaded into the RRMD sensor unit in the Space Shuttle 'Columbia' and an identical box was left in the NASA John F. Kennedy Space Center (KSC) as a control. 'Columbia' (flight No. STS-65) was launched from KSC in Florida, USA on July 8, 1994. The mission duration was 14.75 days and after 'Columbia' returned to earth, we studied (i) the lethal and mutagenic effects of high-LET cosmic radiation on E. coli mutants and (ii) the relationship between high-LET cosmic radiation and the Mutation Frequency of pZ189 DNA. There were virtually no differences between the cell viabilities of the space and control samples of Escherichia coli KMBL3835 (wild-type), KY383 (lexA-), KY385 (recA-) and KY386 (uvrA-), nor between the Mutation Frequency ratios of the space and control E. coli mutant samples. Furthermore, the survival and Mutation Frequency of the supF gene of pZ189 DNA space samples did not differ from those of the control samples. We concluded there was no cancer risk during this Space Shuttle flight.

Alan Richard Clarke - One of the best experts on this subject based on the ideXlab platform.

  • msh2 status modulates both apoptosis and Mutation Frequency in the murine small intestine
    Proceedings of the National Academy of Sciences of the United States of America, 1999
    Co-Authors: Neil J Toft, Louise Howard, Douglas J. Winton, Jane Kelly, Marleen Dekker, Hein Te Riele, Mark J Arends, A H Wyllie, Geoffrey P Margison, Alan Richard Clarke
    Abstract:

    Deficiency in genes involved in DNA mismatch repair increases susceptibility to cancer, particularly of the colorectal epithelium. Using Msh2 null mice, we demonstrate that this genetic defect renders normal intestinal epithelial cells susceptible to Mutation in vivo at the Dlb-1 locus. Compared with wild-type mice, Msh2-deficient animals had higher basal levels of Mutation and were more sensitive to the mutagenic effects of temozolomide. Experiments using Msh2-deficient cells in vitro suggest that an element of this effect is attributable to increased clonogenicity. Indeed, we show that Msh2 plays a role in the in vivo initiation of apoptosis after treatment with temozolomide, N-methyl-N′-nitro-N-nitrosoguanidine, and cisplatin. This was not influenced by the in vivo depletion of O6-alkylguanine-DNA-alkyltransferase after administration of O6-benzylguanine . By analyzing mice mutant for both Msh2 and p53, we found that the Msh2-dependent apoptotic response was primarily mediated through a p53-dependent pathway. Msh2 also was required to signal delayed p53-independent death. Taken together, these studies characterize an in vivo Msh2-dependent apoptotic response to methylating agents and raise the possibility that Msh2 deficiency may predispose to malignancy not only through failed repair of mismatch DNA lesions but also through the failure to engage apoptosis.

  • p53, Mutation Frequency and apoptosis in the murine small intestine
    Oncogene, 1997
    Co-Authors: Alan Richard Clarke, Louise Howard, David J. Harrison, Douglas J. Winton
    Abstract:

    Normal function of the p53 gene is integral to the cellular response to genotoxic stress. One prediction arising from this is that p53 deficiency results in an increased Mutation Frequency. However, limited evidence has been produced in support of this idea. In order to further investigate the in vivo role of p53 in surveillance against Mutation, and particularly to address the significance of p53-dependent apoptosis, we scored Mutation Frequency at the Dlb-1 locus within cells of the intestinal epithelium of animals which were wild type, heterozygous or null for p53 and heterozygous (a/b) at the Dlb-1 locus. Using this assay we have shown that loss of a p53-dependent apoptotic pathway is associated with the detectable acquisition of Mutations, but only at high levels of DNA damage. These results question the significance of the immediate `wave' of p53-dependent apoptosis seen in this tissue, particularly as there was a delayed p53-independent apoptotic pathway. We conclude that loss of p53 function only becomes relevant to the in vivo acquisition of Mutations and thus tumorigenesis in certain circumstances.