The
            <i>miaA</i>
            Mutator Phenotype of
            <i>Escherichia coli</i>
            K-12 Requires Recombination Functions

Zhao, Jing; Leung, Hon‐Chiu Eastwood; Winkler, Malcolm E.

doi:10.1128/jb.183.5.1796-1800.2001

Cited by 24 publications

(16 citation statements)

References 35 publications

(40 reference statements)

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“…The mutA allele differs from the wild-type (glyV ϩ ) tRNA gene by a single base substitution that alters the anticodon in such a way as to promote Asp3Gly mistranslation in mutA cells. Subsequent to this finding, other work revealed that mutations in many other genes that specify tRNAs (10,26) or tRNA-modifying enzymes (32) lead to a similar phenotype presumably mediated by mistranslation. Moreover, exposure to streptomycin, an antibiotic known to promote mistranslation, induces a very similar phenotype in cells bearing certain mutations in rpsL, the gene specifying the 30S ribosomal protein S12 (6).…”

mentioning

confidence: 99%

Escherichia coli Cells Bearing a Ribosomal Ambiguity Mutation in rpsD Have a Mutator Phenotype That Correlates with Increased Mistranslation

Balashov

Humayun

2003

J Bacteriol

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Escherichia coli cells bearing certain mutations in rpsD (coding for the 30S ribosomal protein S4) show a ribosomal ambiguity (Ram) phenotype characterized by increased translational error rates. Here we show that spontaneous mutagenesis increases in Ram cells bearing the rpsD14 allele, suggesting that the recently described translational stress-induced mutagenesis pathway is activated in Ram cells.

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confidence: 99%

Escherichia coli Cells Bearing a Ribosomal Ambiguity Mutation in rpsD Have a Mutator Phenotype That Correlates with Increased Mistranslation

Balashov

Humayun

2003

J Bacteriol

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“…Characteristically, mutations in miaA cause broad pleiotropic phenotypes, including decreased growth rate and yield, broad changes in the biosynthesis and utilization of certain amino acids, defects in translation efficiency and fidelity (especially of specific regulatory genes), increased susceptibility to antibiotics and reduced virulence [32,54]. For example, cellular yields of miaA mutants in S. enterica sv.…”

Section: Discussionmentioning

confidence: 99%

Disruption of MiaA provides insights into the regulation of phenazine biosynthesis under suboptimal growth conditions in Pseudomonas chlororaphis 30-84

Wang

Pierson

et al. 2017

Microbiology

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Many products of secondary metabolism are activated by quorum sensing (QS), yet even at cell densities sufficient for QS, their production may be repressed under suboptimal growth conditions via mechanisms that still require elucidation. For many beneficial plant-associated bacteria, secondary metabolites such as phenazines are important for their competitive survival and plant-protective activities. Previous work established that phenazine biosynthesis in Pseudomonas chlororaphis 30-84 is regulated by the PhzR/PhzI QS system, which in turn is regulated by transcriptional regulator Pip, two-component system RpeA/RpeB and stationary phase/stress sigma factor RpoS. Disruption of MiaA, a tRNA modification enzyme, altered primary metabolism and growth leading to widespread effects on secondary metabolism, including reduced phenazine production and oxidative stress tolerance. Thus, the miaA mutant provided the opportunity to examine the regulation of phenazine production in response to altered metabolism and growth or stress tolerance. Despite the importance of MiaA for translation efficiency, the most significant effect of miaA disruption on phenazine production was the reduction in the transcription of phzR, phzI and pip, whereas neither the transcription nor translation of RpeB, a transcriptional regulator of pip, was affected. Constitutive expression of rpeB or pip in the miaA mutant completely restored phenazine production, but it resulted in further growth impairment. Constitutive expression of RpoS alleviated sensitivity to oxidative stress resulting from RpoS translation inefficiency in the miaA mutant, but it did not restore phenazine production. Our results support the model that cells curtail phenazine biosynthesis under suboptimal growth conditions via RpeB/Pip-mediated regulation of QS.

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“…Removal of miaA results in an ϳ50-fold increase in GC ¡ TA transversions (31) ( Table 2). While the cascade of events that promotes mutations in ⌬miaA mutant populations is far from clear, several clues indicate that it is associated with translational stress-induced mutagenesis (33). Our screen also identified a central regulator of iron homeostasis (fur) (35) whose removal yields a mutator phenotype.…”

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confidence: 94%

“…Defects in and downregulation of these genes are frequently associated with pathogenic populations, indicating a central role for this pathway during bacterial adaptation in nature (22,24,32). Second, defects in tRNA modification due to miaA deletion cause reduced fidelity and efficiency of translation (33). This gene encodes a tRNA dimethylallyltransferase and is involved in hypermodification of the A37 base of certain tRNAs (34).…”

mentioning

confidence: 99%

Genomewide Screen for Modulators of Evolvability under Toxic Antibiotic Exposure

Méhi

Bogos

Csörgő

et al. 2013

Antimicrob Agents Chemother

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Antibiotic resistance is generally selected within a window of concentrations high enough to inhibit wild-type growth but low enough for new resistant mutants to emerge. We studied de novo evolution of resistance to ciprofloxacin in an Escherichia coli knockout library. Five null mutations had little or no effect on intrinsic antibiotic susceptibility but increased the upper antibiotic dosage to which initially sensitive populations could adapt. These mutations affect mismatch repair, translation fidelity, and iron homeostasis. For many antimicrobial agents-including fluoroquinolones, cephalosporins, and rifamycins-a prominent factor contributing to the evolution of resistance is the acquisition of chromosomal mutations during therapy (1-3). While a wealth of highthroughput studies have investigated the impact of individual genes on intrinsic antibiotic susceptibility (4-6) or persistence (7), no systematic large-scale study has been devoted to the identification of molecular mechanisms that promote the evolution of antibiotic resistance.Here we systematically tested the impact of gene inactivation on the de novo evolution of antibiotic resistance. Escherichia coli is undoubtedly an ideal model prokaryote for such a study. The availability of a nearly complete single gene deletion library (the KEIO collection) enables the study of this issue in nearly all of the nonessential genes of this species (8). Our investigations concentrated on understanding the development of resistance to ciprofloxacin. It is one of the most widely deployed fluoroquinolone antibiotics in clinics, and its mechanism of action has been well studied (9-11).We developed a simple, high-throughput protocol that allows investigation of the de novo evolution of quinolone resistance in thousands of parallel bacterial cultures. Our goal was to identify genotypes (i.e., single-gene knockout strains) that permit adaptation to high antibiotic concentrations demanding the acquisition of one or more rare mutations (12, 13). All experiments were conducted with 96-deep-well plates containing 350 l LB medium supplemented with a toxic concentration of ciprofloxacin (200 ng/ml). The antibiotic dosage used is more than 10 times the MIC for wild-type (WT) E. coli (Table 1). About 10 8 cells were added to each well (two replicate populations per genotype). Following 5 days of incubation (37°C, 320 rpm), 2 l of each culture was transferred to an agar plate containing the same concentration of the antibiotic. After 24 h, the resistant bacteria of each genotype were counted. Initial positive hits (i.e., at least one resistant population per genotype) were validated with new sets of laboratory experiments. We used the same procedure as above with 96 replicate populations per genotype. Final hits were checked for the presence of the appropriate gene deletion by PCR using site-specific primers. At such a high ciprofloxacin concentration, the toxic effect of the antibiotic is substantial and population size rapidly declines (14). Typically, WT cultures became extinc...

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The miaA Mutator Phenotype of Escherichia coli K-12 Requires Recombination Functions

Cited by 24 publications

References 35 publications

Escherichia coli Cells Bearing a Ribosomal Ambiguity Mutation in rpsD Have a Mutator Phenotype That Correlates with Increased Mistranslation

Escherichia coli Cells Bearing a Ribosomal Ambiguity Mutation in rpsD Have a Mutator Phenotype That Correlates with Increased Mistranslation

Disruption of MiaA provides insights into the regulation of phenazine biosynthesis under suboptimal growth conditions in Pseudomonas chlororaphis 30-84

Genomewide Screen for Modulators of Evolvability under Toxic Antibiotic Exposure

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